Brain Blogger » Neuroscience & Neurology Health and Science Blog Covering Brain Topics Thu, 16 Apr 2015 13:53:40 +0000 en-US hourly 1 Microglia – Part 1, Definitions and Developmental Progression Sun, 12 Apr 2015 12:00:45 +0000 One of the more remarkable advances in neuroscience, perhaps on par with Santiago Ramon y Cajal’s Neuron Doctrine (the theory that distinct neurons are the functional units of the brain), is the discovery of microglia — appropriately by Cajal’s student Pio del Rio Hortega.

Since their discovery, microglia have been the center of controversy in many contexts (i.e. ontogeny, neurodevelopment, synaptic plasticity, disease, etc.). This is not an overstatement. For example, Hortega surmised (correctly), back in the 1920s, that these cells hailed from the mesoderm, rather than the neuroectoderm (like all other brain cells) during an organism’s development.

This prediction, however, was not definitively verified until seven decades later, when it was demonstrated that microglia do not populate the neuroectoderm until embryonic day eight. This insight generated further questions, including: from where do these alien cells specifically originate? This question of microglial ontogeny and other definitions will be the focus of Part I of a five part series on the role of microglia in brain function from development to disease, as potential therapeutic targets and culminating with a fun — possibly unexpected — look at futuristic directions.

First, let us define some important terms. Unfortunately, many contemporary authors continue to use antiquated terminology when discussing microglia and this has become somewhat debilitating to the field (not to mention a pet peeve of mine). In 1908, Elie Metchnikoff won the Nobel Prize for his work on phagocytosis, or “cellular act of eating,” which later lead to his description of the macrophage system. This system is made up of cells collectively called mononuclear phagocytes, resulting in what is now called the mononuclear phagocyte system. It is this classification to which the microglial cell fits. Microglia are, after all, the tissue resident phagocytic cells of the brain.

Now, for the purpose of this article, I would like to define two more classification terms: “circulating” monocytes and “tissue-resident” macrophages. This distinction is important developmentally. It was recently demonstrated that circulating and tissue-resident cells arise from temporally and spatially different stem cell pools. For example, nearly all of our organs contain macrophages specifically designed to function within that organ, mainly performing maintenance duty. These tissue-resident macrophages derive from a developmental organ known as the yolk sac (most anatomists might call it an umbilical vesicle now), which is the sight of primitive hematopoeisis (or blood production). In other words, macrophages designed to function in a specific tissue are made first from a special pool of hematopoeitic stem cells and then leave the yolk sac to colonize their respective organs — such as microglia in the brain, Langerhans cells in the skin, or Kupfer cells in the liver. On the other hand, circulating monocytes are produced in the bone marrow later on in development, have a high turn over rate, and are continually produced over a lifetime. These cells mostly meander through the blood and lymphatic system and usually die after becoming activated — not necessarily so for tissue-resident macrophages.

So, it was shown in 2011 in the journal Science for the first time, that microglial ontogeny begins in the yolk sac. From there, they travel through the newly developed blood stream to reach the brain before the aptly named blood brain barrier closes — forever shunning the entry of any other type of mononuclear phagocyte. Here they spend the rest of their lives actively surveying surrounding brain tissue (among other roles to be discussed in following articles), providing a homeostatic milieu for the brain to function efficiently.

This brings us to our last set of definitions: surveillance, primed, activated and dystrophic microglia. I will not go deeply into each category, but I think it is important to understand that microglia are the most dynamic cells in the brain with their unique ability to transition between these activation states.

I would also like to emphasize that these states are contextual and do not necessarily describe a microglial cell as beneficial or destructive to surrounding brain tissue, but instead are responses to molecular cues necessitating some microglial effector function. For example, a microglial cell can be activated in both developmental synapse pruning (beneficial) and phagocytosis of viable neurons during disease (detrimental). No matter what, microglia are never resting — a term that has also deluded the field — but in constant motion within defined, non-overlapping locales.

You can find a live video I have taken of a retinal microglia in this state here. Instead of “resting” microglia, they are more appropriately termed surveillance microglia, as they extend and retract their processes, feeling around the adjacent tissue, sensing the environment.

Primed microglia describes the state between surveillance and activation. One could think of it as a pre-activation state, where they begin showing signs of morphological changes (i.e. shortening and thickening of their processes) and expression of certain molecules.

From there, microglia become fully activated, taking on a rounded (amoeboid) shape and expressing high levels of molecules associated with inflammation and/or phagocytosis.

Lastly, dystrophic describes a dysfunctional state of microglia, in which their processes begin to fragment or even fuse with other microglia. This is usually associated with chronic activation during disease and not usually part of their functional spectrum. These definitions are currently in a state of flux as the field tries to develop a cohesive theory of microglial function.

When looking at a fluorescent image of a mature, surveying microglia, one will notice how elegantly their processes radiate from the small cell body, forming complex, arborous structures. This is not their perpetual morphologic state. On the contrary, they are born as small, amorphous blobs, reminiscent of peripheral macrophages. In fact, their morphological development is the reverse of their transition through activation states. It is not until they enter the developing brain that they begin to ramify. Once they enter, microglia spread out to evenly tile the entire brain, taking up their positions as noble sentinels.

Research is ongoing to determine what molecular cues developing microglia receive (and from where, but probably the brain) to drive their migration into the brain. A few candidate molecules (e.g. CSF-1, IL-34, TGF-beta; no need to memorize these) have been implicated. It can be imagined that as microglia develop from primitive macrophages in the yolk sac, such molecules would create a signaling gradient that microglia, expressing corresponding receptors, would follow to reach their final desination. Think of leaving a trail of biscuits for your stubborn puppy to follow if you want to get her into the kennel.

Once they enter the brain, what keeps them there and in that complex, ramified morphology? What induces them to clear developmentally apoptotic neurons and prune synapses, both to allow appropriate, efficient wiring of the brain? Again, we think we have some ideas, but the precise molecular mechanisms remain unclear. What is clear, however, is that this area of microglial research is still blossoming and constant strides are being made to understand the development of these frenetic little cells.

This could lead us to some interesting insights that will facilitate therapies for diseases where microglia seem to have a role; a topic we will cover in Part III of this series. Now that we have an idea of microglial ontogeny, we will next discuss what role they play in the healthy developing and adult brain in Part II of Microglia.


Alliot F, Godin I, & Pessac B (1999). Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain research. Developmental brain research, 117 (2), 145-52 PMID: 10567732

Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, & Merad M (2010). Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science (New York, N.Y.), 330 (6005), 841-5 PMID: 20966214

Gomez Perdiguero E, Klapproth K, Schulz C, Busch K, Azzoni E, Crozet L, Garner H, Trouillet C, de Bruijn MF, Geissmann F, & Rodewald HR (2015). Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature, 518 (7540), 547-51 PMID: 25470051

Kaufmann SH (2008). Immunology’s foundation: the 100-year anniversary of the Nobel Prize to Paul Ehrlich and Elie Metchnikoff. Nature immunology, 9 (7), 705-12 PMID: 18563076

Rezaie P, & Male D (2002). Mesoglia & microglia–a historical review of the concept of mononuclear phagocytes within the central nervous system. Journal of the history of the neurosciences, 11 (4), 325-74 PMID: 12557654

Image via Johan Swanepoel / Shutterstock.

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The Link Between Breastfeeding and IQ Wed, 08 Apr 2015 12:00:03 +0000 It is indeed a pity that in recent times, breastfeeding has grabbed headlines for a slew of controversial reasons. Remember the ruckus some people made about women breastfeeding in public? Well, they got rightly trounced by the saner and the more considerate members of the public. But the flurry of mud-slinging and Twitter rants brought into the open a disturbing fact — many people are still unaware of the transformative physical and mental health benefits of breastfeeding on children.

Many doctors point out that breastfeeding helps new mommies shed the weight they have gained during pregnancy. But as men of science, they should also point out the positive link between breastfeeding and higher IQ of children. After all, this has been proved conclusively in countless studies.

The Effect of Early-Life Diet on IQ

Studies have already conclusively proved the impact of early-life diet on the brain structure of human beings. One study was conducted on two groups of adolescents who were respectively fed on a standard diet and a highly-nutritious diet in the weeks after they were born. The findings show that those adolescents who were on a high nutrient diet had significantly greater verbal IQ than the group that was on a regular diet. This study encouraged scientists to research more on the long-term cognitive benefits of breastfeeding.

Another, more recent investigation has conclusively proven the link between breastfeeding and white matter development, which is related to IQ. It demonstrated that exclusive breastfeeding is related to increase in the volume of white matter throughout the brain and that of the gray matter in the sub-cortical region. Exclusive breastfeeding is also related to the excess thickness of the parietal lobe cortical region.

Scientists have found that the duration of breastfeeding is also a critical factor that determines the mental development of the child. The longer the duration, the more is the cognitive and motor development in children. This finding was reported from a study on 2- and 3-year-old children who were breastfed for various lengths of time.

The Positive Effects of Breastfeeding Evident Well Into Adulthood

Scientists are excited to note that the positive effects of breastfeeding continue to manifest long after adolescence and well into adulthood. A decades-long study was undertaken in Brazil to determine the long-term benefits of exclusive breastfeeding. Breastfeeding information of close to 6,000 infants from various demographic groups was recorded in 1982. After 30 years, the scientists tracked down more than half of the original participants and recorded their IQ levels, educational qualifications, and incomes. The findings were startling.

Infants who were breastfed for 12 months or more scored more on IQ tests, had greater educational attainment, and earned more than those infants who were breastfed for less than a month. The positive correlation between high IQ and both greater educational attainment and income-earning potential is evident, but the findings of this study prove that it is not just breastfeeding that matters. The duration of breastfeeding plays a critical role in the cognitive development of infants.

This is the first study to examine the long-term effects of breastfeeding. The findings of this study should now encourage physicians to educate their patients on the benefits of exclusive breastfeeding at least for the first six months of the baby’s life and continuing the practice well into the first year of age. Hospitals too should encourage breastfeeding amongst new mothers.

What’s in Breastfeeding: The DHA Link

Although it is known that breast milk is rich in all the nutrients that the baby needs to mature intellectually and physically, scientists are not yet sure about the exact mechanisms at work. But they strongly believe that DHA has a role to play.

Docosahexaenoic (DHA) and arachidonic (AA) acids comprise about 20 percent of the fatty acid content in the human brain. Fatty acids are known to promote healthy neuronal growth and repair and myelination. Myelination or the increase in the volume of myelin (a protective layer of protein and fatty substances) around the neurons improves neuronal coordination and enhances brain functionality especially with regards to higher cognitive tasks. Breast milk contains an abundance of long-chain fatty acids like DHA and AA. So scientists believe that there could be a strong DHA link in the positive relation between breastfeeding and higher IQ.

The above findings have critical lateral considerations. Physicians could prescribe DHA supplements to pregnant women, so there is placental transmission of this fatty acid that would, in turn, aid the neural development in the fetus. Lactating mothers can take these supplements in prescribed doses to boost the concentration of DHA in their milk. Infant formula manufacturers should also invest in research and development to determine the optimal amount of DHA they should include in their products.

Breastfeeding, Oxytocin, and Brain Development

Some scientists also believe that the hormone oxytocin may have a role to play in facilitating brain development in breastfed babies. Oxytocin is present in small amounts in maternal milk. Animal studies suggest that oxytocin is also produced by the body in response to the suckling action of babies feeding on mother’s milk.

Oxytocin has long been associated with increased bonding and trust between the mother and the child. But according to more recent data, oxytocin is also instrumental in shaping and supporting the physical development of the central nervous system. It regulates the functions of the autonomic nervous system to ensure smooth motor functioning. Oxytocin also acts as a neural protective agent and heals scarred tissues. So it is evident that the presence and release of oxytocin in the infant body indirectly enhances his mental capabilities by promoting and supporting healthy brain development.

The findings from the above-mentioned studies leave no room for doubt that infants who have been exclusively breastfed for the first six months of their lives grow up to be more happy, healthy, and intelligent than their formula-fed peers. Mothers, are you taking note?


Bernard, J., De Agostini, M., Forhan, A., Alfaiate, T., Bonet, M., Champion, V., Kaminski, M., de Lauzon-Guillain, B., Charles, M., & Heude, B. (2013). Breastfeeding Duration and Cognitive Development at 2 and 3 Years of Age in the EDEN Mother–Child Cohort The Journal of Pediatrics, 163 (1), 36-420 DOI: 10.1016/j.jpeds.2012.11.090

Carter, C. (2014). Oxytocin Pathways and the Evolution of Human Behavior Annual Review of Psychology, 65 (1), 17-39 DOI: 10.1146/annurev-psych-010213-115110

Deoni, S., Dean, D., Piryatinsky, I., O’Muircheartaigh, J., Waskiewicz, N., Lehman, K., Han, M., & Dirks, H. (2013). Breastfeeding and early white matter development: A cross-sectional study NeuroImage, 82, 77-86 DOI: 10.1016/j.neuroimage.2013.05.090

Deoni, S., Mercure, E., Blasi, A., Gasston, D., Thomson, A., Johnson, M., Williams, S., & Murphy, D. (2011). Mapping Infant Brain Myelination with Magnetic Resonance Imaging Journal of Neuroscience, 31 (2), 784-791 DOI: 10.1523/JNEUROSCI.2106-10.2011

Guesnet, P., & Alessandri, J. (2011). Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) – Implications for dietary recommendations Biochimie, 93 (1), 7-12 DOI: 10.1016/j.biochi.2010.05.005

Isaacs, E., Gadian, D., Sabatini, S., Chong, W., Quinn, B., Fischl, B., & Lucas, A. (2008). The Effect of Early Human Diet on Caudate Volumes and IQ Pediatric Research, 63 (3), 308-314 DOI: 10.1203/PDR.0b013e318163a271

Krol, K., Rajhans, P., Missana, M., & Grossmann, T. (2015). Duration of exclusive breastfeeding is associated with differences in infants’ brain responses to emotional body expressions Frontiers in Behavioral Neuroscience, 8 DOI: 10.3389/fnbeh.2014.00459

Victora, C., Horta, B., de Mola, C., Quevedo, L., Pinheiro, R., Gigante, D., Gonçalves, H., & Barros, F. (2015). Association between breastfeeding and intelligence, educational attainment, and income at 30 years of age: a prospective birth cohort study from Brazil The Lancet Global Health, 3 (4) DOI: 10.1016/S2214-109X(15)70002-1

Image via MitarArt / Shutterstock.

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Best and Worst of Neuroscience and Neurology – March 2015 Mon, 06 Apr 2015 11:00:44 +0000 In this article, I will present a selection of publications that came out in March. There were many interesting developments, both in fundamental neuroscience and neurology, and in the practical aspects of dealing with brain-related diseases and disorders.

In March, the scientific community marked the birthday of Sir Bernard Katz, German-born biophysicist who received the 1970 Nobel Price in Physiology and Medicine for his investigations of the properties of synapses. Together with Paul Fatt, Sir Katz discovered that neural transmitters are released into the synapses in defined “quantal” portions. The underlying mechanism of exocytosis relies on the release of neurotransmitters from the vesicles of approximately equal size, thus giving this seemingly quantum property to the process of neural transmission. The works of Bernard Katz laid foundation to the modern understanding of the processes of neural transmission.


Last month, we saw quite a few interesting and encouraging publications on the development of treatments for Alzheimer’s disease. All of these new approaches are still in their infancy, but the important thing is that they demonstrate not only the slowing down of disease development but also the possibility of restoring, at least partially, normal brain functions.

New anti-tau immunotherapy for Alzheimer’s

The oligomers of tau proteins are considered as one of the major culprits in the development and progression of Alzheimer’s disease. Scientists from the University of Texas tested the effect of new anti-tau immunotherapy on experimental animals with Alzheimer’s. It turned out that a single dose of immunotherapy reversed the memory deficit in animals. It also reduced the level of beta amyloid oligomers, the building blocks of notorious amyloid plaques that are always seen in the brains of patients with the disease. Clearly there is a cross-talk between two molecular components, since immunotherapy targeted directly only one of them.

Existing drugs to treat Alzheimer’s?

Two existing drugs have also been found active in reversing the effects of Alzheimer’s disease. An existing drug to treat epilepsy, levetiracetam, was found to be able to restore memory and brain functions in patients with amnestic mild cognitive impairment, which is considered an early stage of Alzheimer’s disease. The drug was tested in the first human trial and was shown to improve memory performance in the patients.

Another drug, AZD05030, was developed to treat cancer but failed clinical trials. Surprisingly, it turned out to be effective for Alzheimer’s disease, restoring the memory and brain cell connections in the experimental animals. The compound will soon be tested in clinical trials on humans.

Ultrasound to activate microglial cells

But the most interesting news, in my opinion, came from Australia. Researchers at the University of Queensland have developed a non-invasive ultrasound method that activates microglial cells making them to digest and remove the amyloid plaques. The treatment temporarily opens the blood-brain barrier thus allowing activation of mechanisms that clear away the toxic protein agglomerates from the brain. In the mice with Alzheimer’s disease, the treatment restored the memory to the healthy levels. If this approach will work in humans at least to some degree, it will most certainly represent a breakthrough in the treatment of Alzheimer’s disease.

The differences in young and old brains according to fMRI

Alzheimer’s disease is often considered as one of the common aspects of aging. But in general, the age-related negative changes in brain functions are traditionally viewed as a reflection of changes in the underlying neuronal activity. This view is challenged by new data obtained by researchers from the University of Cambridge.

The scientists re-examined methodology that is used to measure the brain activity, the functional magnetic resonance imaging (fMRI). The problem with fMRI is that it measures neural activity indirectly through changes in regional blood flow. This means that the differences in age-related vascular reactivity should be taken into account when neuronal differences are measured. Researchers used the resting state fMRI measurements from 355 healthy volunteers over their lifetime to get the baseline measures of vascular functions. Once these new baseline data were taken into account, the differences in neuronal activity between young and old brain turned out to be not so big, thus suggesting that they were overestimated in previous studies. The changes in the aging brain are likely to be caused primarily by the vascular changes.

Opening the blood-brain barrier with radiowaves

One of the reasons we have so few therapeutics to target brain diseases is the lack of reliable brain-specific drug delivery systems. The next article provides a radically different approach to address this problem.

Localized and specific drug delivery to the problem site in the body was always viewed by pharmaceutical scientists as a highly desirable aim which is, unfortunately, very difficult to achieve. With 98% of modern drugs unable to cross the blood-brain barrier, the brain is a particularly difficult part of the body to target selectively. A new approach reported by Canadian scientists this month sounds almost futuristic.

They developed a method of delivering magnetic nanoparticles to the specific areas of the brain using the magnetic fields generated by MRI machine. Once there, the nanoparticles can be made to by vibrate and dissipate heat using a radio-frequency field. This creates a mechanical stress that opens a blood-brain barrier locally and for a limited period of time (around 2 hours), thus allowing the delivery of blood-circulating therapeutics into the brain. The method has only been proven on the animals so far, but it appears to be a highly promising strategy for treating multiple brain disorders.

Free will for all?

Fundamental mechanisms of brain functioning continue to attract the attention of neuroscientists. In particular, we are interested in the characteristics of human brain that are unique to us. Free will is among those things that we see as making us who we are.

Well, the newly published study casts certain doubts on this self-glorifying view. It appears that even the animals as simple as worms have free will. Once tempted by the smell of tasty food, they may chose to go and investigate, but may also ignore it altogether and move in another direction. The brain of the microscopic roundworm Caenorhabditis elegans has only 302 neurons and 7,000 synapses. This is a nice simple model for investigating the function of neural systems.

Researchers found that the particular response of the individual worm to the stimulus depends on the current state of a simple three-cell neuronal system in its brain. This system can be influenced by competing motivations, and the final behavioral response is formed on the basis of input provided from all neurons. In general, this is not so different from the responses observed in much more complex brains. And probably this finding should not be so surprising. After all, free will is not just a philosophical concept – it also has lots to do with the decision-making processes in the brain.


As usual, this month we have seen a number of publications that have changed our views on some important issues. We may consider them as negative developments, but gaining any knowledge is always a positive thing.

Potential uses for brain stem cells may be limited

Stem cell therapy is one of the buzz words in the scientific community these days. The possibilities promised by this therapeutic approach are exciting. The discovery of stem cells in the brain brings hope that they can be used to treat a broad range of brain conditions, from neurodegenerative diseases to injuries. However, the new findings of German scientists will probably be seen as a certain setback for such high hopes. The researchers found that the diversity of neurons formed from them is limited. Also, the number of brain stem cells decreases with age. Further research will need to be focused on finding the ways to extend the ability of these cells to renew themselves.

We know less than we thought about inflammation in the brain

It is not uncommon to see scientific research yielding unexpected results. One of these such occasions was reported recently by the scientists from the University of Manchester studying stroke. It is well known that stroke is associated with inflammatory response which, instead of aiding recovery, cause further damage. Researchers were studying stroke-associated inflammasomes, large protein complexes mediating the inflammation and contributing to the cell death. One of such complexes called NLRP3 is known to be associated with injuries. Currently, the inflammasome NLRP3 is a target for developing the drugs against neurodegenerative diseases such as Alzheimer’s that is accompanied by inflammation.

To the researchers’ surprise, it turned out that NLRP3 has nothing to do with the inflammation processes in brain. Instead, two other protein complexes, NLRC4 and AIM2, are involved in the stroke and brain injury. The finding provides new targets for developing the stroke treatments, but also demonstrates once more how little we know about the inflammatory and immune processes in the brain.

Common treatments don’t always produce the results we want

Three publications below shed some light on why certain well established and commonly used treatments do not exactly produce the results we want.

Only in my previous monthly review I was mentioning that our knowledge of the mechanisms of anti-depressant drugs is limited at best. A new article published this month once again confirms this statement. It is generally believed that depression is caused by the imbalance in serotonin signalling. In response to the neuronal firing, serotonin is released from the vesicles in the presynaptic terminals into the synapse. Serotonin is then taken back into the terminals in the process which is targeted by the serotonin re-uptake inhibitors. The action of these drugs increases the level of serotonin in the synapses and thus normalize its balance affected during the depression.

It turned out, however, that exocytosis is not the only process for the serotonin release. The neuromediator can also simply diffuse through the cell membrane. The excessive level of serotonin may affect the firing of serotonergic neurons by autoinhibition, thus leading to the initial slowing down of the antidepressants’ therapeutic action.

HIV remains the largest pandemic in human history. Despite the decades of research and impressive success of anti-retroviral therapy, the complete cure for the disease remains elusive. The largest obstacle on the way to such cure is the presence of reservoirs in the body where the virus can safely hide from the circulating drugs. The brain is one of these reservoirs.

New data published this month show that the virus may infiltrate in the brain as early as four months after the initial infection. Once in the brain, virus may establish a relatively isolated sub-population which is mostly shielded from the drugs by the blood-brain barrier. Unfortunately, very little is currently known about the HIV replication inside the brain. Medical professionals commonly advise the HIV patients not to start the therapy immediately to avoid the long-term side effects of the drugs. Delaying the therapy, however, clearly helps the virus to establish itself in “safe havens” like brain, as current research demonstrates.

Obesity is one of the major risk factors in the development of type II diabetes. But the remarkable thing about the drugs for type II diabetes, such as thiazolidinediones, is that they make people to gain even more fat! Common sense would tell anyone that something is clearly wrong with these drugs. Now we know exactly what this is.

The drugs act directly on the so-called agouti-related protein (AgRP) cells, the hunger-stimulating cells located in the hypothalamus. Activation of these cells in experimental animals makes them immediately hungry. No wonder people treated by anti-diabetics feel much stronger food cravings. And obviously, something should be done with this whole approach to treat diabetes.


Bakker, A., Albert, M., Krauss, G., Speck, C., & Gallagher, M. (2015). Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance NeuroImage: Clinical, 7, 688-698 DOI: 10.1016/j.nicl.2015.02.009

Calzolari, F., Michel, J., Baumgart, E., Theis, F., Götz, M., & Ninkovic, J. (2015). Fast clonal expansion and limited neural stem cell self-renewal in the adult subependymal zone Nature Neuroscience, 18 (4), 490-492 DOI: 10.1038/nn.3963

Castillo-Carranza, D., Guerrero-Munoz, M., Sengupta, U., Hernandez, C., Barrett, A., Dineley, K., & Kayed, R. (2015). Tau Immunotherapy Modulates Both Pathological Tau and Upstream Amyloid Pathology in an Alzheimer’s Disease Mouse Model Journal of Neuroscience, 35 (12), 4857-4868 DOI: 10.1523/JNEUROSCI.4989-14.2015

Denes, A., Coutts, G., Lénárt, N., Cruickshank, S., Pelegrin, P., Skinner, J., Rothwell, N., Allan, S., & Brough, D. (2015). AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3 Proceedings of the National Academy of Sciences, 112 (13), 4050-4055 DOI: 10.1073/pnas.1419090112

Garretson, J., Teubner, B., Grove, K., Vazdarjanova, A., Ryu, V., & Bartness, T. (2015). Peroxisome Proliferator-Activated Receptor   Controls Ingestive Behavior, Agouti-Related Protein, and Neuropeptide Y mRNA in the Arcuate Hypothalamus Journal of Neuroscience, 35 (11), 4571-4581 DOI: 10.1523/JNEUROSCI.2129-14.2015

Gordus, A., Pokala, N., Levy, S., Flavell, S., & Bargmann, C. (2015). Feedback from Network States Generates Variability in a Probabilistic Olfactory Circuit Cell DOI: 10.1016/j.cell.2015.02.018

Kaufman, A., Salazar, S., Haas, L., Yang, J., Kostylev, M., Jeng, A., Robinson, S., Gunther, E., van Dyck, C., Nygaard, H., & Strittmatter, S. (2015). Fyn inhibition rescues established memory and synapse loss in Alzheimer mice Annals of Neurology DOI: 10.1002/ana.24394

Leinenga, G., & Gotz, J. (2015). Scanning ultrasound removes amyloid-  and restores memory in an Alzheimer’s disease mouse model Science Translational Medicine, 7 (278), 278-278 DOI: 10.1126/scitranslmed.aaa2512

Mlinar, B., Montalbano, A., Baccini, G., Tatini, F., Palmini, R., & Corradetti, R. (2015). Nonexocytotic serotonin release tonically suppresses serotonergic neuron activity The Journal of General Physiology, 145 (3), 225-251 DOI: 10.1085/jgp.201411330

Sturdevant, C., Joseph, S., Schnell, G., Price, R., Swanstrom, R., & Spudich, S. (2015). Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection PLOS Pathogens, 11 (3) DOI: 10.1371/journal.ppat.1004720

Tabatabaei, S., Girouard, H., Carret, A., & Martel, S. (2015). Remote control of the permeability of the blood–brain barrier by magnetic heating of nanoparticles: A proof of concept for brain drug delivery Journal of Controlled Release, 206, 49-57 DOI: 10.1016/j.jconrel.2015.02.027

Tsvetanov, K., Henson, R., Tyler, L., Davis, S., Shafto, M., Taylor, J., Williams, N., Cam-CAN, ., & Rowe, J. (2015). The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults Human Brain Mapping DOI: 10.1002/hbm.22768

Image via anyaivanova / Shutterstock.

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The Dream Of Your Dreams Mon, 30 Mar 2015 11:00:45 +0000 Lucid dreaming is one of those things few people think in depth about, even if they’ve had one or two. Still it’s a skill which some people become absolutely fascinated with honing, and having had a fair few of them myself I’m beginning to see why.

Lucidity, as some argue, can be an endless opportunity which is only limited to your imaginative capacity. You can explore any area of your own mind, from base hedonistic fantasy to sublime self-discovery. Discourse with dream characters plucked from your own psyche, learn to play a Beethoven sonata accompanied by the Philharmonic, or simply step into your favourite novel.

Of course while enthralling, the practice itself isn’t quite so easy. Often when lucidity dawns a first-timer will be so excited by the experience they promptly wake up! Once this first obstacle is overcome, there’s still a long road between knowing one is asleep, and being able to choose the direction of the dream.

The technique that’s worked best for me in recent months has been a very simple variety of what is known as a WILD – a Wilfully Induced Lucid Dream. These are attempted when awakening from a fairly long period of sleep and then returning to sleep. The particular method I’ve found success with is simply to await the moment you feel yourself about to fall asleep again, and then alternately press the tips of two fingers against the duvet or pillow for a minute or two while repeating an intention in my mind to become lucid.

There are a host of other methods available, and the academic who really established the field of oneirology, Stephen LaBerge, also pioneered the creation of a device which, while no longer available, purported to aid in lucid dream induction, the NovaDreamer. Several similar bits of kit have followed in its wake, and there are rumours of a NovaDreamer II in development from the original team.

The best of these devices, such as the REM Dreamer, play flashing lights and sounds from a sleep mask worn at night which detects rapid eye movement. A new project in the crowdfunding works is Aurora from iWinks, which promises a technologically up-to-the-minute version of the same and is said to be coming out this summer.

These devices’ use is debated within this somewhat specialist yet very passionate field, not in terms of whether they genuinely assist in inducing lucidity (the better designed devices at least appear to do so), but in terms of whether their use will have a built in time-limit for success.

Our minds have a great ability to become used to external stimuli and to “build them into” a dream, such that we don’t notice their intrusion. This is why becoming lucid at the onset of dreaming, or via a trained habit of thought are considered by many oneironauts to be superior techniques. They are internalised methods, and therefore sustainable over the long-term.

One radical step (some may say too far!) is the recent research published in Nature by Ursula Voss and colleagues into weak electrical field bombardment of the brain to induce lucidity. These researchers found that frequencies of 40 Hz created gamma wave brain states which aided the likelihood of lucidity occurring in sleepers. I for one won’t be trying this anytime soon. I think there are pretty strong arguments against risking sending electric signals directly to the frontal lobes to improve my odds at achieving something I can simply accomplish using my own mental faculties.


Voss, U., Holzmann, R., Hobson, A., Paulus, W., Koppehele-Gossel, J., Klimke, A., & Nitsche, M. (2014). Induction of self awareness in dreams through frontal low current stimulation of gamma activity Nature Neuroscience, 17 (6), 810-812 DOI: 10.1038/nn.3719

Image via KI Petro / Shutterstock.

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Human Head Transplants – Fantasy to Fact? Thu, 26 Mar 2015 11:00:03 +0000 When English author Mary Shelley penned Frankenstein in 1818, little did she know that her vision might come true, albeit in a slightly different way and as a boon to mankind. Shelley’s Victor Frankenstein created the Monster by sewing together body parts from human corpses. In a way, Frankenstein created Life. Doctors and surgeons today do nothing different; they save lives by transplanting organs, bones, skin, and nerves and veins. To date, they can transplant almost every major organ of the body, like the heart, liver, lungs, kidneys, pancreas, and intestine, but not the head. This may be about to change!

Italian neurosurgeon Dr. Sergio Canavero recently created quite a stir by his announcement that he will attempt the head transplant surgery within three years. He believes that modern medicine already has the means to do this procedure successfully.

Unsurprisingly, Cavanero’s announcement was met with harsh criticism. Mainstream media dutifully covered the potential moral and ethical problems associated with head transplantation. In this article, I’d like to analyse how much science is really behind the Dr. Cavanero’s thinking and whether such surgery can really be done at present time. This is an aspect of the problem which was mostly ignored by the reporters concerned with the ethics.

The Precursor

Although heads have not been transplanted in human beings, this procedure has been attempted in monkeys. In 1970, Robert White and his team transplanted the head of a monkey on to the body of another monkey. The removal of the head and the transplantation was carried out simultaneously. The monkey lived for 8 days, and there were no surgical complications. However, this experiment did not address the challenge of reconnecting the severed spinal cords to prevent paralysis. So no head transplantation experiment in monkeys or humans has been attempted since.

But Dr. Canavero says he has come up with a way to reconnect spinal cords in human beings during a head transplant.

Head Transplant in Humans: The Way Forward

Dr. Canavero has named his human head transplant project HEAVEN. A person who is possibly suffering from an incurable and debilitating medical condition but has a healthy and functioning head and brain will be the recipient. A person who has been declared brain-dead but still has a healthy body will be the donor. So after the procedure, the donor will receive a new head.

Dr. Canavero believes that inducing hypothermia during the transplantation procedure and using sharp severing instruments and specialized healing agents will help him overcome many of the challenges inherent in the procedure.

Human Head Transplant Challenge #1: Sustaining Life After the Head is Severed

The biggest challenge during the human head transplant procedure is to stabilize and keep alive the individual after his head is severed and blood flow stops. Research data show that human beings can be sustained without blood flow if the body is cooled to a temperature range of 12oC and 15oC. At these temperatures, the metabolic activity in the cerebral region drops to about 10 percent of what is normal. The data from cardiac surgery has revealed that producing profound hypothermia causes total cessation of circulation. These conditions can be safely sustained for about 45 minutes without causing any neurological damage to the individual.

Canavero believes 45 minutes is adequate time for the surgeons to reconnect the severed spinal cords.

Human Head Transplant Challenge #2: Preventing Cell Damage in the Spinal Cord Stumps

Dr. Canavero realizes that reattaching the severed spinal cords is not enough to merit a complex and costly head transplant procedure. The individual who has received the new head should be able to regain some of his earlier motor abilities. This implies that the heads should be severed with as little damage to the neuronal cells, so it is easy to restore the connections, and consequently, motor functionality.

According to clinical findings, there have been several instances where patients with sharp wounds to their spinal cords not only survived but also recovered from their initial stages of paralyses and regained their earlier range of motor functionality. On the other hand, one clinical study on the victim of a self-inflicted 0.38 caliber gunshot (with greater scar area) reveals that the patient did not recover from his state of paralysis.

Another study has found that axons have to be regenerated to restore neurological functionality in cases where the damaged nerve is separated by a gap. Axon generation is most effective when this gap is less than two centimeters in length.

So the challenge in human head transplantation is to minimize the scar area when severing the spinal cords. Dr. Canavero proposes using a specialized severance tool that will minimize the scar area and keep cell damage to a minimum. He has in mind the tools that will create the force of less than 10 N during transections. Incidentally, a typical spinal cord injury involves the force of around 26,000 N.

Dr. Canavero believes that an ultra-sharp nanoknife made from a layer of silicon nitride could be used to inflict a sharp cut.

Human Head Transplant Challenge #3: Healing, Regenerating Neurons, and Restoring Connections and Motor Functionality

The chances of restoring the donor’s earlier level of motor abilities increases greatly the faster the severed cords join and the damaged membranes are repaired. And the faster the healing process, the quicker the neural connections will be restored. Usually in healthy individuals, the body’s natural healing mechanisms swing into action when there is a cut or a wound. But to heal the spinal cord tissues in a case of head transplant, Dr. Canavero proposes using a compound called polyethylene glycol (PEG).

According to several research studies, PEG has the ability to heal wounds or reseal at the molecular level. In fact, scientists are already exploring avenues to establish PEG as an effective means of managing and/or treating spinal cord injury and restore or improve motor functionality in patients.

Dr. Canavero also intends to apply electrical stimulation at the point where the two severed ends of the cords fuse to accelerate healing. It has been established that electrical stimulation not only speeds up the axons and dendrons regeneration but can also trigger voluntary movements in individuals with chronic complete paralysis.

Human Head Transplant Challenge #4: Post-Transplant Complications

Organ rejection and poor or impaired blood flow to the transplanted organ are some common post-transplant complications. However, medicine has the means to diagnose these conditions and intervene effectively. For instance, the presence of a couple of serum protein biomarkers confirms acute rejection in renal transplant patients.

Color Flow Doppler (CFD) ultrasonography has been found to be an effective way to monitor blood flow after surgery. These monitoring and diagnostic methods may be implemented to detect post-transplant complications in people who have received a new head.

Every great scientific breakthrough sounds incredulous at first. The idea of a head transplant in humans may sound fantastic, dreadful or ridiculous, depending on your personal position, but I have no doubt that eventually it could be done.

Potential benefits for certain patients are obvious. If human head transplant is successful, paraplegics who have substantial amounts of spinal cord intact and people suffering from muscular dystrophy can dream of an independent and self-sufficient future where they are back to doing the things they love and are able to live more productive lives. Yet, there is also no doubt that the possibility of successful human head transplantation will create serious concerns in many quarters.


Angeli, C., Edgerton, V., Gerasimenko, Y., & Harkema, S. (2014). Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans Brain, 137 (5), 1394-1409 DOI: 10.1093/brain/awu038

Canavero, S. (2013). HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI) Surgical Neurology International, 4 (2) DOI: 10.4103/2152-7806.113444

Canavero, S. (2015). The “Gemini” spinal cord fusion protocol: Reloaded Surgical Neurology International, 6 (1) DOI: 10.4103/2152-7806.150674

Chen, R., Sigdel, T., Li, L., Kambham, N., Dudley, J., Hsieh, S., Klassen, R., Chen, A., Caohuu, T., Morgan, A., Valantine, H., Khush, K., Sarwal, M., & Butte, A. (2010). Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions PLoS Computational Biology, 6 (9) DOI: 10.1371/journal.pcbi.1000940

KHALID, A., QURAISHI, S., ZANG, W., CHADWICK, J., & STACKJR, B. (2006). Color doppler ultrasonography is a reliable predictor of free tissue transfer outcomes in head and neck reconstruction Otolaryngology – Head and Neck Surgery, 134 (4), 635-638 DOI: 10.1016/j.otohns.2005.11.031

Kuffler, D. (2014). An assessment of current techniques for inducing axon regeneration and neurological recovery following peripheral nerve trauma Progress in Neurobiology, 116, 1-12 DOI: 10.1016/j.pneurobio.2013.12.004

Malhotra, S., Dhama, S., Kumar, M., & Jain, G. (2013). Improving neurological outcome after cardiac arrest: Therapeutic hypothermia the best treatment Anesthesia: Essays and Researches, 7 (1) DOI: 10.4103/0259-1162.113981

Rad, I., Khodayari, K., Hadi Alijanvand, S., & Mobasheri, H. (2015). Interaction of polyethylene glycol (PEG) with the membrane-binding domains following spinal cord injury (SCI): introduction of a mechanism for SCI repair Journal of Drug Targeting, 23 (1), 79-88 DOI: 10.3109/1061186X.2014.956668

Image via Family Business / Shutterstock.

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The Physiology and Psychology of Pain Thu, 19 Mar 2015 11:00:38 +0000 Pick up any newspaper and pore over it. Not only are nations at war but communities in the same country are fighting amongst themselves. People are killing each other for a piece of land, money, or just because they hate a person who looks different from them or worships another God. In the midst of these gory tales of hatred are the stories of triumph — men and women who give up their lives to save others and doctors who put their lives in the line of fire to treat people in far-flung places and war-torn regions.

Why do some people hurt others while others live just to bring a smile on other people’s faces?

Why do some people cause so much pain to others while some dedicate their lives to heal the wounds of strangers?

According to scientists, the perception of pain in oneself and recognizing it in others (empathy) is influenced by the complex interplay of neural circuitry in the individual, biochemical reactions in his brain, societal conventions, and evolutionary mechanisms.

The Perception of Pain in Self

Physical pain has a distinct brain signature. Functional magnetic resonance imaging (fMRI) can evaluate the amount of pain. However, another study has built on these findings to suggest that people “feel” physical pain differently. This difference stems from the way their brains are wired.

According to one recent study, the experience of pain has two distinct neural stages or pathways. The first stage kicks off, say, when you accidentally burn your fingers or cut your hand. The nerves in your hand send signals to the brain. The pain stimuli reach parts of the brain, like the anterior cingulate cortex, that are associated with the perception of pain. The chain of events that make up this stage is similar in all healthy individuals.

But people “react” differently to pain; not everyone utters an “ouch” or reaches out for a painkiller when they are physically hurt. The researchers who took part in the above study now know why. They have discovered a second neural pathway instrumental in the perception of pain. The “feeling” of pain — mild, intense, or unbearable — is determined by the activity in the medial prefrontal cortex and nucleus accumbens. These two regions of the brain are conventionally associated with motivation and emotion.

Scientists now know there are definite emotional and cognitive underpinnings to the perception of pain. This indicates that individuals can regulate and/or alter their perception of pain through mental conditioning techniques like meditation, distraction, and visualization. People who suffer from debilitating pain, triggered by a disease or an injury, can now hope to find relief in coping mechanisms other than popping painkillers.

The Societal Context of Feeling Pain

The perception of pain has a societal basis as well. Several studies have found that individuals tend to report different levels of pain in presence or absence of a highly-empathic person, like a romantic partner, and a complete stranger. Women tend to report less pain in the presence of an “attachment figure” or someone who makes them feel safe. In an experiment, women subjects in a threatening situation showed greater activity in the region of their brains that triggers safety signals (that is, they felt less pain) when they were shown images of their romantic partners.

One study, however, clarifies that the perception of pain in such cases is actually determined by the attachment style of the subject.

Individuals with anxious attachment styles crave close and intimate relationships but tend to sacrifice their needs to keep their partners happy. They are not confident about their partner’s affections and fear the relationship will not last. According to the findings from the above study, women with this attachment style tend to feel more pain in the presence of a person who does not empathize with their conditions. They feel lower pain in the presence of their romantic partners who are perceived to be highly empathic.

Individuals with avoidant attachment styles tend to value independence and self-sufficiency more than intimacy. These people are not comfortable sharing their feelings with strangers and partners alike. So it is not surprising that studies indicate that women with such attachment styles report lesser pain when alone than when in the presence of another individual, who may be a stranger or a romantic partner.

With these findings, doctors may now need to think twice before they ask individuals to be present when their partners are giving birth. It seems that there is no rule of thumb.

The Perception of Pain in Others

Human beings are social animals. The ability to live harmoniously in a society, care for others, and form enduring relationships depends on the quality of empathy. So it is natural that scientists should be curious to know why some people are more empathetic than others or if some situations naturally bring out more empathy.

Scientists believe that empathy is triggered by various cognitive and affective processes. Few years ago a study was carried out on subjects with congenital insensitivity to pain (CIP) to understand if painful experiences from the past influenced the ability to empathize with the pain of others. People with CIP cannot feel anything when subjected to painful stimuli. So they have no “experience” or memory of pain. But curiously, as was found in the study, they can empathize with the pain of others by seeing and hearing pain-related behavior in video clips.

But do you think that emotional cues of pain like seeing groaning and writhing are so powerful that they can move one and all? Unfortunately, no. Empathy is more complex than that.

A new article published this year reports that human beings tend to be more empathetic towards friends than strangers. The study also noted that stress tends to affect the ability to empathize. Individuals who are under stress tend to be less empathic to the pain of strangers than when they are relaxed and peaceful.

The latter finding may explain mob violence or why violence tends to increase during social uprisings. Stress is a powerful trigger that can make people act in a way they would not think about in other situations.

The mechanisms underlying empathy are complex. But it is crucial that scientists delve more into them because it seems that understanding empathy is akin to decoding violent behavior. And the world could certainly do with a lot less violence!


Danziger, N. (2006). Is pain the price of empathy? The perception of others’ pain in patients with congenital insensitivity to pain Brain, 129 (9), 2494-2507 DOI: 10.1093/brain/awl155

Decety, J. (2011). The neuroevolution of empathy Annals of the New York Academy of Sciences, 1231 (1), 35-45 DOI: 10.1111/j.1749-6632.2011.06027.x

Eisenberger, N., Master, S., Inagaki, T., Taylor, S., Shirinyan, D., Lieberman, M., & Naliboff, B. (2011). Attachment figures activate a safety signal-related neural region and reduce pain experience Proceedings of the National Academy of Sciences, 108 (28), 11721-11726 DOI: 10.1073/pnas.1108239108

Krahe, C., Paloyelis, Y., Condon, H., Jenkinson, P., Williams, S., & Fotopoulou, A. (2015). Attachment style moderates partner presence effects on pain: a laser-evoked potentials study Social Cognitive and Affective Neuroscience DOI: 10.1093/scan/nsu156

Martin LJ, Hathaway G, Isbester K, Mirali S, Acland EL, Niederstrasser N, Slepian PM, Trost Z, Bartz JA, Sapolsky RM, Sternberg WF, Levitin DJ, & Mogil JS (2015). Reducing social stress elicits emotional contagion of pain in mouse and human strangers. Current biology : CB, 25 (3), 326-32 PMID: 25601547

Sambo, C., Howard, M., Kopelman, M., Williams, S., & Fotopoulou, A. (2010). Knowing you care: Effects of perceived empathy and attachment style on pain perception Pain, 151 (3), 687-693 DOI: 10.1016/j.pain.2010.08.035

Wager, T., Atlas, L., Lindquist, M., Roy, M., Woo, C., & Kross, E. (2013). An fMRI-Based Neurologic Signature of Physical Pain New England Journal of Medicine, 368 (15), 1388-1397 DOI: 10.1056/NEJMoa1204471

Woo, C., Roy, M., Buhle, J., & Wager, T. (2015). Distinct Brain Systems Mediate the Effects of Nociceptive Input and Self-Regulation on Pain PLoS Biology, 13 (1) DOI: 10.1371/journal.pbio.1002036

Image via Tyler Olsen / Shutterstock.

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What Have Your Glia Done For You Today? Mon, 16 Mar 2015 11:00:43 +0000 How should we approach solving the most fundamental questions in neuroscience? Some would say that our current endeavors into mapping the complement of neuronal connections (the connectome) within the human brain will bring us the most fruitful gains; and they could be right. This is the main focus of several (expensive) big data initiatives such as the BRAIN Initiative, the Human Connectome Project and the Human Brain Project.

However, a major shortcoming of these projects is the lack of goals slated to mapping the other half of the brain; a complement of cells known as glia, of which there are three predominant populations. These cells make up fifty percent of the total brain volume and are integral to normal brain function. A complete understanding of the brain’s “support cells”, as they are also called, along with mapping the neuronal wiring, will be paramount for a global theory of how the brain works to bring about consciousness and our plethora of behaviors.


Neuroglia consist mainly of astrocytes, oligodendrocytes and microglia, the last of which do not actually originate in the brain. Instead, microglia (my current field of research), originate in the fetal yolk sac (a structure involved in primitive hematopoesis, or blood formation) where many other primitive and tissue resident macrophages are born. Contrary to original theories, microglia migrate into the brain early in embryonic life and reside there as a stable, self-sustaining population of cells, which are never replaced by bone marrow-derived cells from the periphery.

In essence, unlike other glia, our microglia grow old with us. As a pool of tissue-specific macrophages, microglia constitute the immune cells of the central nervous system. They are capable of mounting an immune response against foreign invaders (e.g. blood cells or proteins and bacteria) as well as clear neuronal debris after injury. As such, they have, somewhat insultingly, been dubbed the “garbage men of the brain.”

It has become clear that this is short-sighted. For example, microglia mediate the elimination of supernumerary synapses from the developing brain through a mechanism known as phagocytosis. Essentially, they gobble up the unnecessary synapses that the brain generates during development, a process without which many developmental and behavioral abnormalities can occur. Understanding this process is thus essential for determining how the brain’s connections are wired.

Extending their services into postnatal life, microglia also maintain the status quo within the brain. For example, when microglia are completely depleted from the central nervous system, adult mice show deficits in learning. In other words, your microglia can make you smarter through learning-induced synaptic remodeling; they act to balance removal of unused or inappropriate synapses allowing neuronal energy expenditure to be allocated to forming efficient synapses.

What important programs do these little “electricians” employ to bring about an appropriately wired brain? How can we manipulate them to prevent or curb neurological and mental illnesses? These are important questions that the neuroscientific community is currently asking, but must be put into the wider framework of mapping the human brain.


Astrocytes (or astroglia) perform the most diverse set of functions of the glial cells, including sharing with microglia the role of synaptic maintenance. How could they not? A single astrocyte can contact up to one million synapses. At the microstructure level this is known as the “tri-partate synapse”.

It is at this juncture of the pre- and post-synaptic clefts (where the electrical signal of one neuron is coupled via a chemical signal – a neurotransmitter – to the next neuron) and the astroglial process, that astrocytes do most of their work. Here, they can regulate the rate and strength of synaptic transmission across neurons by releasing or sequestering neurotransmitters and modifying extracellular ion concentrations. Not only do they “listen” and “talk” to neurons, but they also provide metabolic support of endothelial cells, which line the brain vasculature, making up the blood brain barrier. At this site, they are also well positioned to regulate the amount of blood flow to a local brain region.

Recently, astrocytes have made public headlines with the discovery of their involvement in bulk clearance of brain metabolic waste during sleep, the importance of which is not lost on us after staying up too late the night before an exam.


Oligodendrocytes (oligos for short), the central nervous system equivalent of the Schwann cell in the peripheral nervous system, wraps a fatty sheath around the axons of neurons. This sheath known as myelin provides insulation to the axon and allows for much faster propagation of the electrical signal and thus faster communication and transmission of information. Think of it as the insulation around electrical wires on your favorite appliance.

Oligos seem to only function in this capacity, but we do not actually know that – a rough search on PubMed shows about 25 times more papers are published on neurons than oligodendrocytes. For example, a study published this week in the journal Science found that oligos are much more diverse than previously known. The study authors found that this cell type alone could be sub-divided into six classes based on their molecular signatures. We do not yet know the function of each or how each type may play a role in brain cytoarchitecture to facilitate faster, more efficient neuronal signaling, but it should become a priority.

Each of the glial functions listed above (and we have left out other types of glia, such as Bergmann glia, NG2 glia and ependymal cells, but we know even less about them) are essential to global brain plasticity and learning. Because of their intimate relationship with neurons, glial cells hold a central position in influencing cognitive processes. Author of The Other Brain, R. Douglas Fields suggested in a Nature Comment:

“[That] these include processes requiring the integration of information from spatially distinct parts of the brain, such as learning or the experiencing of emotions, which take place over hours, days and weeks, not in milliseconds or seconds.”

In other words, because glia work on the slower chemical level, not via electrical signals, they may facilitate paradigms such as learning, which do not happen instantaneously like say, visual perception. I could not agree more. But at this time, we can only speculate as to how glia might impart their “magical elixir” on neurons, facilitating the workings of the most complex biological entity in the known universe.

Over a century after the start of glial research, we still lack fundamental knowledge of glial numbers, diversity, distribution throughout the brain and function in the context of neurons and between themselves. The “neurotechnologies” that arise from the neurocentric initiatives should additionally be allocated to studying these questions.

If our minds, which emerge from the tangled wet mass of neurons, make us who we are, then paraphrasing my mentor’s mantra sums it up best: What have your glia done for you today?


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Image via Jose Luis Calvo / Shutterstock.

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Klotho and the Thread of Life – Can We Delay Aging? Sat, 14 Mar 2015 11:00:24 +0000 In Greek mythology, the Fates, or Moirae, were the goddesses who controlled humans’ destiny, from the time they were born to the time they died. The three sisters, Clotho, Lachesis and Atropos, daughters of Zeus and Themis, controlled the thread of human life.

Each Fate had a task: Lachesis was the apportioner, she measured the thread and decided how much lifetime was to be allowed; Atropos, the inevitable, cut the thread choosing when mortals would die; Clotho was the spinner, she spun the thread of a person’s life.

Clotho was the inspiration for naming klotho – a gene that somehow also seems to spin the thread of life. Klotho was another of so many serendipitous discoveries in science: while studying the phenotype of transgenic mice overexpressing another gene, there was an accidental insertion of ectopic DNA in a region of the klotho gene, inhibiting its expression. Makoto Kuro-o and colleagues, from the National Institute of Neuroscience, in Tokyo, Japan, thus found, in 1997, that disruption of the klotho gene caused accelerated aging. Later, it was found that the opposite also happened: by overexpressing klotho in mice, aging was significantly delayed and a longer lifespan was acquired.

The Journal of Neuroscience’s February article, showing that klotho can decrease premature mortality and enhance spatial learning and memory in a mouse model of Alzheimer’s disease piqued my curiosity about this protein. Obviously, the discovery of klotho generated massive research interest – a protein that may stop aging is the Holy Grail of life sciences, I reckon.

But how much is known about klotho? Can it really delay aging in humans?

Although the discovery of klotho has boosted the understanding of the aging process, its function is still not fully understood. In humans, serum levels of klotho decrease with age after 40 years old. This decrease is also observed in patients with several aging-related diseases. But most of what is known so far comes from animal research studies.

Although klotho is mainly produced in the kidneys and in the brain choroid plexus, mutations to its gene cause widespread aging phenotypes, probably due to circulating klotho. Deficiency has been associated with hypertension, renal failure, decreased insulin production and increased insulin sensitivity, early diabetic nephropathy, ectopic calcification in various soft tissues, arteriosclerosis, among others. Increased klotho expression, on the other hand, has been linked to reduced tumor proliferation and anti-inflammatory effects. In the brain, klotho deficiency in mice induced memory deficits, hippocampus degeneration, a reduction in synapses, and impaired axonal transport and myelin production.

Most of these phenotypes seem to be associated with defective calcium metabolism. Klotho seems to be essential in the maintenance of the levels of calcium and phosphorus by negatively regulating the synthesis of active vitamin D; abnormal activation of vitamin D due to klotho insufficiency has actually been shown to lead to degeneration of the dopaminergic system associated with Parkinson’s disease. Klotho also seems to act by increasing the expression of antioxidant enzymes and conferring resistance to oxidative stress, known to cause significant DNA damage.

Klotho and neurodegeneration

Myelin is an insulating material that envelops neurons, being essential for the correct functioning of the nervous system. Altered myelin production is a characteristic of the normal aging process of the brain. In fact, age-related cognitive decline seems to be mostly associated with loss of myelin rather than loss of neurons. There are experimental evidences suggesting that klotho is a key regulator in myelin biology by promoting and maintaining myelination. Therefore, it is possible that the loss of klotho expression may account for the age-related cognitive decline through decreased myelin production.

This link between cognitive decline, myelin abnormalities and klotho downregulation places it as a potential therapeutic target for neuroprotection against myelin-associated age-dependent changes. Compounds that increase klotho expression may therefore become important therapeutic tools for the treatment of neurodegenerative diseases, such as multiple sclerosis and Alzheimer’s disease. Increasing klotho levels may protect myelin integrity and prevent myelin degeneration in the aged brain and promote repair in multiple sclerosis.

This may be quite a wondrous molecule.

Maybe one day we will use klotho to prevent neurodegeneration and keep our brains young. Could we carry out a body transplant when our bodies get old, and use our cloned, younger body? Too much science fiction? Probably. But we once thought we couldn’t go to the Moon.


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Image via Twin Design / Shutterstock.

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Predicting Your Brain From Birth? Mon, 09 Mar 2015 11:00:17 +0000 Genetic sequencing is already changing the way we see ourselves. In February, the FDA announced approval for commercial “consumer genetics” company 23andMe to market a test for Bloom Syndrome. Whole genome sequencing is becoming faster and cheaper. But what might we do with this knowledge and how will it alter both society and us as individuals? Novel The Generation explores these questions.

Like the rest of her generation, the novel’s female protagonist, Freya, has her genome sequenced shortly after birth. Amongst other things, the results predicted early-onset Parkinson’s disease. She has been told to expect her symptoms to manifest when she reaches thirty or thirty-one, and has regular scans to track changes in her brain. We first meet Freya on the evening of her twenty-ninth birthday, finding her understandably subdued:

“They say I should really start to see the symptoms manifest themselves in the next year or so. I won’t just be clumsy, the drugs won’t be enough anymore and they won’t be able to hide it. I’m having another brain scan next week. I’m terrified.”

One theme of The Generation looks at whether our belief in a diagnosis could influence how we physically respond to it. Could a nocebo-type effect – an “anti-placebo” – actually induce symptoms?

It’s already been well-documented by research that the nocebo effect is real. Simply warning someone that a needle “may sting” can actually cause such pain to become a reality for the patient.

Researchers at the Technical University of Munich in Germany published a comprehensive report of the nocebo effect, examining 31 empirical studies. They concluded that the effect is common and ought to be taken into consideration by healthcare professionals on an everyday basis. One of the studies they analyzed looked at 50 people with chronic back pain, who were given a flexibility test. Half were told beforehand that the test might cause some pain, while the others were not. Many more patients in the first group claimed that the flexibility test did actually cause them pain.

As we undoubtedly discover more about our individual susceptibility to disease, such findings demonstrate that the psychological effects of that knowledge are likely to have repercussions. Medical professionals will need to carefully handle their patients’ preconceptions and fears, as well as their own.

Indeed, could medical professionals also be influenced by such predictions?

Later in the novel, Freya describes her most recent scan:

The neurologist had said he could see no marked worsening since the last scan, which had come as a pleasant surprise. Had she been having migraines? Any problems with coordination, digit or limb control? He had looked confused as he peered at the screen. Freya had replied affirmatively and he then looked perceptibly relieved. When I’m tired, she had said, at the end of a hard week at work, or if I’ve been to the gym and not eaten properly. He had nodded and tapped some notes into the computer. Well, that’s to be expected, he had said.

Do we – and more specifically, medical professionals – only see what we expect to see? You only have to take a look at some of the most popular optical illusions to begin to accept that this may be a possibility.

The “checker shadow illusion” is an image that tricks our brains into thinking that square in the “shadow” of the cylinder (B) is a different shade to one outside it (A). In reality, they are exactly the same color.


The creator of the illusion Edward H. Adelson, Professor of Vision Science at MIT in 1995, explains why our reaction to the image says a lot about our brain’s desire to find meaning:

“As with many so-called illusions, this effect really demonstrates the success rather than the failure of the visual system. The visual system is not very good at being a physical light meter, but that is not its purpose. The important task is to break the image information down into meaningful components, and thereby perceive the nature of the objects in view.”

The Generation envisages a near-future world in which all manner of medical issues and character traits – criminality, sexuality, academic ability – are defined at birth. And perhaps this may one day be feasible. Not only is the field of genetics on the road to this possibility, but understanding more about neurogenetics and neuroscience may expand the limits of our current understanding of the brain.

A recent review of brain imaging studies, published in Neuron, highlights the ways in which an increasing range of traits and susceptibilities can be predicted by MRIs and other neuroimaging techniques. The authors suggest that neuromarkers may offer “opportunities to personalize educational and clinical practices that lead to better outcomes for people”.

Despite the seriousness of the situation, Freya never tired of seeing her brain appear before her, first in two dimensions and then in three, digitally overlaid with fluorescent colours so that it ended up looking like something that belonged on the wall of a nightclub rather than inside her head. It always looked so strange, so otherworldly in its folds and holes, like the topography of a long-lost land. She had nothing to compare it to though, not really. Each brain is different, her neurologist had told her, which initiated the spark of a thousand questions she had wanted to ask him but had not, afraid to break the silence of the room. Hers, apparently, was just too different. Different enough that it would be her end.

Could it be, as one character muses, that “no matter how advanced modern science becomes, no matter how deeply our genes and our brains can be probed, no one can ever discover the subtleties of your character, the element of your spirit that makes you you.”?

The questions I raise in The Generation essentially relate to how far science can take us in our understanding of ourselves and our identity. I’m sure that we will soon begin to see answers to that question emerge.

The Generation is available now from Amazon, Kobo, NOOK and Google Play.


FDA News Release (February 19, 2015). FDA permits marketing of first direct-to-consumer genetic carrier test for Bloom syndrome. Accessed online 7 March, 2015.

Gabrieli, J., Ghosh, S., & Whitfield-Gabrieli, S. (2015). Prediction as a Humanitarian and Pragmatic Contribution from Human Cognitive Neuroscience Neuron, 85 (1), 11-26 DOI: 10.1016/j.neuron.2014.10.047

Häuser W, Hansen E, & Enck P (2012). Nocebo phenomena in medicine: their relevance in everyday clinical practice. Deutsches Arzteblatt international, 109 (26), 459-65 PMID: 22833756

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The Hollywood Medical Reporter – The Mind Behind “Brain Games” Sun, 08 Mar 2015 11:00:55 +0000 This Emmy-nominated series tests the ultimate supercomputer – your brain. Back for its fifth season, Brain Games uses a host of interactive games, experiments and, yes, even magic tricks to expose and explain some of the most complex regions of the brain. We sat down with Executive Producer, Michael J. Kovnat, to discuss the truly mind-altering show.

BB: Can you share one thing you knew about the brain that made you want to work on this show, and one thing you’ve learned about the brain since you began work on it?

MK: I had heard that the brain is the most complex known structure in the universe – which had seemed hyperbolic. As I’ve dived into working on the show, I’ve come to appreciate what that means – and all the surprising ways our awareness arises from this three pound organ. As one example, our episode on color gets into how your subjective experience of red, green, etc. has to do with how your photoreceptors interact with other brain cells, and that system can be easily fooled and confused.

 BB: What can you tell us about the inception of Brain Games?

MK: The idea was to create a show that would invite the audience to play along with a series of perception experiments. Over time, that concept was refined by a number of very talented producers, writers, and executives.

BB: Can you share a bit about your background and how you eventually began working on this show?

MK: I’d been producing non-fiction television for about 20 years, and had developed a sub-specialty in science programming. When I was hired as a staff executive producer at Nat Geo Channel, Brain Games was already in its second season. It was the first project I lobbied to work on when I was hired.

BB: More than mindless entertainment, this show demands an interactive viewing experience. That being said, what is the ultimate goal you wish to achieve through people watching this show?

MK: We want to inspire viewers to get curious about how their brains work, and hopefully change their perceptions on everyday actions. We’re making the processes of the brain come to life through interactive experiments that will keep viewers guessing and wanting more.

BB: How do you go about choosing both the human subjects for the interactive experiments on the show, as well as the experts/guest(s)?

MK: The team reaches out to people in a variety of ways. Experts are usually sought out based on their published work in the subject area of an episode. Other participants are solicited online or approached on the street.

BB: Has the show changed and/or developed in any obvious or not-so-obvious ways over the seasons?

MK: The show has actually gone through many changes over the seasons. It premiered as unhosted, hour-long specials. Then it became half hours and Jason Silva was brought in as a host. The tone and style has shifted slightly season to season. And more changes are coming soon!

BB: Can you share any details with us about what viewers can expect to see in the rest of Season 5

MK: This summer, you’ll see new episodes covering topics such as scams, positive thinking, and the surprising differences and similarities between human and animal brains. We want to ask big questions, always seen through the lens of how the brain works.

BB: Is Brain Games meant for a particular audience or viewer, and has that changed at all over the seasons?

MK: The ideal viewer is really any curious person. We’ve found that people in just about every demographic have found something they love about Brain Games. Viewers play along and get interested in the “why” behind the “wow.”

The following questions refer to episodes featuring Magician, Eric LeClerc:

BB: How would  you compare the two worlds of science and magic?

MK: Magic, done honestly, can provide an excellent guide to gaps in human attention. These tricks show how easily the brain can be fooled. Many magicians, like scientists, are first-rate skeptics.

BB: What is your favorite magic-trick?

MK: Any trick where my mind appears to have been read. Gets me every time.

BB: How do you decide what insights about the brain as well as the corresponding magic-tricks and interactive brainteasers to feature on a given episode? Does one typically come before the other? How much collaboration is required and does that collaboration ever involve outside consultation?

MK: Typically, we start with a show topic or theme. Then we work with magicians to come up with related illusions.

BB: How do you find ways to distill all the complex scientific insights you discuss on the show into viewer-friendly material that is not simply related in understandable terms, but can resonate as well? How, if any, do the “magical” aspects employed play a role in this?

MK: Just as a good magician never reveals his or her tricks, I don’t want to give away all our secrets. But when we use illusions in the show, they function as a fun way to call attention to the gap between what you expect and what’s really happening. That can be an entertaining way into a complex scientific idea.

BB: In that same vein, how do you balance the incredibly complex element of science with the goal of entertainment? Does one ever get in the way of the other?

MK: This is really an entertainment-driven show. The science comes along for the ride, but if we can’t entertain, viewers won’t watch.

Image via Linda Bucklin / Shutterstock.

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Best and Worst of Neuroscience & Neurology – February 2015 Sat, 07 Mar 2015 20:00:22 +0000 In February we have seen, yet again, quite a few new exciting developments in neuroscience and neurology. There were interesting findings in both theoretical neuroscience and in more practical applications aimed at studying various brain conditions and diseases.

Please do note, of course, that the choice of which articles to include in the monthly review is highly subjective. The content of this review mostly reflects my personal opinion about their significance.

On 23 February, the scientific community marked the birthday of Allan McLeod Cormack who received the Nobel Prize in Physiology and Medicine in 1979 for invention of computer-assisted tomography. Allan Cormack’s research laid theoretical foundation to this method back in the early 1960s. It would be probably worth mentioning that Cormack’s original papers on the subject initially attracted very little interest, until Godfrey Hounsfield constructed the first CT scanner in 1971 based on Cormack’s theoretical concept. Allan Cormack is rightfully considered the father of modern computer tomography. These days, the CT-based techniques are actively used by neuroscientists. In fact, a number of findings reviewed below are obtained using various CT methods.

First two articles that I include deal with more theoretical aspects of neurobiology.

For decades, neuroscientists believed that adult brains do not produce new neurons. The discovery that this is not correct challenged this major dogma of neuroscience. The role of these new neurons in behavior and cognition is still not clear, however. The article published this month in Trends in Cognitive Science presents an interesting point of view on this issue.

It is now well known that environment has a profound effect on adult brains. Stress has been shown to decrease the number of new neurons in hippocampus. On the other hand, rewarding experiences stimulated the production of new neurons in this part of the brain. The authors of the report argue that new neurons may serve as a means to fine-tune the hippocampus to the predicted environment. In particular, seeking out rewarding experiences or avoiding stressful experiences may help each individual optimize his or her own brain. Thus, it appears that newly born neurons help us to flourish in the rewarding environment.

The question what make our brain unique (thus eventually making us who we are) remains the biggest unsolved mystery in neuroscience. An article published this month in Science can certainly be viewed as a serious contribution towards finding the answer to this question.

Researchers based in Germany were comparing the genes involved in the development of human brain and brain of mouse. They identified 56 genes preferentially expressed in the human neocortex. The neocortex is the part of the brain explicitly associated with cognitive abilities, and it is significantly enlarged in primates. One of the genes, ARHGAP11B, turned out to be present only in human progenitor cells, the stem cells that divide and form other brain cells during the brain growth and development. Moreover, the scientists found that gene ARHGAP11B is unique for humans and is absent even in chimpanzees, our closest evolutionary relatives. Researchers believe that this gene has contributed to the evolutionary expansion of the human neocortex.

The following two articles are related to the studies of how we learn various skills and how we learn to interact with others.

It is intuitively obvious that younger people and people in old age have different approaches to learning. Scientists from University College London decided to put this assumption to a specific test. They enrolled two groups of participants, one aged 19-35 and another aged 60-73, and assigned them the same numeric task which would require some learning to be finished successfully. Both groups performed with similar degree of success, but utilized two completely opposite strategies. Younger people were learning by integrating different types of information, while older people advanced their learning through ignoring distracting, less important information.

The study shows that the brain works rather differently at different ages, and training can enhance different age-dependent cognitive processes. Among other things, this new insight may help to inform educationists on different age-dependent approaches to teaching.

Our social behavior inevitably requires understanding of others and the ability to anticipate their actions. In fact, this ability is a cornerstone of successful social interaction. This month, researchers from Massachusetts General Hospital-Harvard Medical School Center for Nervous System Repair announced that they had discovered key neuronal elements in the dorsal anterior cingulate cortex involved in the formation of such behavior.

Scientists taught rhesus monkeys to play a game where outcome (and consequent reward) was linked to the ability to anticipate each other’s actions. The neurons in the anterior cingulate were particularly active when an animal was trying to figure out the action of the opponent. The anticipating ability disappeared when scientists artificially disrupted the activity of neurons in anterior cingulate cortex. Researchers believe that their findings will help to pave the way for better understanding and treatment of such conditions as autism and antisocial personality disorder.

This month we witnessed large number of publications related to Parkinson’s disease. There were both positive and negative developments in this area.

Encouraging news came from Sweden: in a first-of-its-kind experiment on humans, scientists injected growth factor PDGF directly into the brains of patients suffering from Parkinson’s disease. PDGF is known to stimulate regenerative processes in the body, and researchers hoped that injections of this substance can stimulate self-repair of brain. The previous trials on animals have shown that this assumption is correct and injections can improve motor functions in mice with Parkinson’s disease.

The human trial was limited to 12 patients only and was aimed to establish the safety of the procedure. No adverse effects were observed in any of the patients during the 85-day follow-up period. The symptoms of Parkinson’s disease are caused by a gradual decrease in the production of neuromediator dopamine. The results of brain tomography before and after the injections demonstrated that the level of dopamine increased in the patients who received PDGF injections, thus indicating the reversal of pathological process. Obviously, this is very exciting news, and the trials now will be taken to the next level in several countries around Europe.

Clinical trials often result in failures. The general public is often unaware of the fact that the overwhelming majority of drug trials get terminated – for a variety of reasons – at the early stages, and the potential drugs never reach patients. A trial for a previously promising treatment for Parkinson’s disease was terminated this month.

Despite decades of research and substantial recent progress in understanding the molecular mechanisms involved, we still have no clinically available drugs capable of stopping or even slowing down the development of Parkinson’s disease. Earlier studies indicated that creatine monohydrate might be capable of slowing down the development of disease’s clinical manifestations. This prompted the National Institute of Neurological Disorders and Stroke to initiate a clinical trial to study the long-term effects of this drug.

Unfortunately, after five years of follow-up, researchers did not noticed any improvements in the patients taking creatine monohydrate compared to patients taking a placebo. The trial was terminated early due to futility.

A number of studies in the past reported the association between the use of statins (cholesterol-lowering drugs) and decreased incidence of Parkinson’s disease. The evidence to support this view, however, was rather inconsistent. New analysis of long-term data published this month revealed that statins don’t have protective effect against the disease. Moreover, in the long term they even increase the risk of this disease’s development. The authors of the report caution against promoting benefits of statins until better understanding of their influence on the body and brain is reached.

Two other publications questioned the safety and efficiency of the methods and treatments that have been used in medical practice for decades.

Millions of surgeries under total anesthesia are performed every year around the world. Anesthesia is not absolutely safe and is associated with a number of risks. It appears that one of such risks is the potential impairment of brain development in young children and babies. Several experts in the field have recently published an article highlighting their concerns.

The concerns are based on two facts. First, anesthetics do kill brain cells in young monkeys. Second, children who experienced multiple exposures to anesthesia early in life are more likely to have learning problems. Both facts do not prove conclusively the danger of anesthetic for the developing human brain, but the findings do call for caution and for further research.

Another review published this month cast the doubts on the wisdom of using anti-depressants targeting the serotonin re-uptake pathway. The theory behind using such drugs states that depression is caused by decreased levels of serotonin in the synapses. However, it is not yet possible to measure directly how serotonin is released and used in the living brain, which makes the foundation of the theory quite shaky.

The authors of the report argue that anti-depressive medications, instead of helping patients, complicate their recovery. This explains why the depressive symptoms tend to get worse in the first two weeks of taking the drugs. It appears that the drugs create obstacles for the natural mechanisms of brain recovery. Many researchers will disagree with the point of view of the authors of this report. Nonetheless, the side effects of antidepressants are well known, and more detailed look into the mechanisms of their action is warranted.

Finally, a new research paper published this month challenged one textbook view that persisted in neuroscience for many years.

The hippocampus has traditionally been thought to be critical for conscious memory but not necessary for unconscious memory processing. Unconscious memory involves things that we can do without having to think about it, such as moving around and performing simple manual tasks. Much of the knowledge about the hippocampus and how our brains organize memory comes from research on amnesia patients.

This theory of unconscious memory system was recently challenged by a new analysis of the data. Results suggest that the hippocampus plays a fundamental role in aspects of memory processing that are beyond conscious awareness. It appears that both conscious and unconscious memory systems rely upon the same neural structures but function in different physiological ways.

The studies listed above as negative developments should not necessarily be viewed as such. By exposing the wrong concepts, they provide substantial contribution to our knowledge and help to advance science.


Addante, R. (2015). A critical role of the human hippocampus in an electrophysiological measure of implicit memory NeuroImage, 109, 515-528 DOI: 10.1016/j.neuroimage.2014.12.069

Andrews, P., Bharwani, A., Lee, K., Fox, M., & Thomson, J. (2015). Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response Neuroscience & Biobehavioral Reviews, 51, 164-188 DOI: 10.1016/j.neubiorev.2015.01.018

Florio, M., Albert, M., Taverna, E., Namba, T., Brandl, H., Lewitus, E., Haffner, C., Sykes, A., Wong, F., Peters, J., Guhr, E., Klemroth, S., Prufer, K., Kelso, J., Naumann, R., Nusslein, I., Dahl, A., Lachmann, R., Paabo, S., & Huttner, W. (2015). Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion Science DOI: 10.1126/science.aaa1975

Haroush, K., & Williams, Z. (2015). Neuronal Prediction of Opponent’s Behavior during Cooperative Social Interchange in Primates Cell DOI: 10.1016/j.cell.2015.01.045

Kieburtz, K., Tilley, B., Elm, J., Babcock, D., Hauser, R., Ross, G., Augustine, A., Augustine, E., Aminoff, M., Bodis-Wollner, I., Boyd, J., Cambi, F., Chou, K., Christine, C., Cines, M., Dahodwala, N., Derwent, L., Dewey, R., Hawthorne, K., Houghton, D., Kamp, C., Leehey, M., Lew, M., Liang, G., Luo, S., Mari, Z., Morgan, J., Parashos, S., Pérez, A., Petrovitch, H., Rajan, S., Reichwein, S., Roth, J., Schneider, J., Shannon, K., Simon, D., Simuni, T., Singer, C., Sudarsky, L., Tanner, C., Umeh, C., Williams, K., & Wills, A. (2015). Effect of Creatine Monohydrate on Clinical Progression in Patients With Parkinson Disease JAMA, 313 (6) DOI: 10.1001/jama.2015.120

Huang, X., Alonso, A., Guo, X., Umbach, D., Lichtenstein, M., Ballantyne, C., Mailman, R., Mosley, T., & Chen, H. (2015). Statins, plasma cholesterol, and risk of Parkinson’s disease: A prospective study Movement Disorders DOI: 10.1002/mds.26152

Cappelletti, M., Pikkat, H., Upstill, E., Speekenbrink, M., & Walsh, V. (2015). Learning to Integrate versus Inhibiting Information Is Modulated by Age Journal of Neuroscience, 35 (5), 2213-2225 DOI: 10.1523/JNEUROSCI.1018-14.2015

Opendak, M., & Gould, E. (2015). Adult neurogenesis: a substrate for experience-dependent change Trends in Cognitive Sciences, 19 (3), 151-161 DOI: 10.1016/j.tics.2015.01.001

Paul, G., Zachrisson, O., Varrone, A., Almqvist, P., Jerling, M., Lind, G., Rehncrona, S., Linderoth, B., Bjartmarz, H., Shafer, L., Coffey, R., Svensson, M., Mercer, K., Forsberg, A., Halldin, C., Svenningsson, P., Widner, H., Frisén, J., Pålhagen, S., & Haegerstrand, A. (2015). Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson’s disease patients Journal of Clinical Investigation, 125 (3), 1339-1346 DOI: 10.1172/JCI79635

Rappaport, B., Suresh, S., Hertz, S., Evers, A., & Orser, B. (2015). Anesthetic Neurotoxicity — Clinical Implications of Animal Models New England Journal of Medicine, 372 (9), 796-797 DOI: 10.1056/NEJMp1414786

Image via Bangkok happiness / Shutterstock.

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Brains in Pain – Apps to the Rescue? Fri, 06 Mar 2015 12:00:24 +0000 It’s a simplification to argue that technology removes us from the concerns of the physical world. Many technological applications are geared specifically to orient us in the world, and none bring us more clearly full circle back to ourselves than mobile apps which focus on our physical and mental health.

One of the lesser known – but vitally helpful – types of apps is the emerging range of technological aids for living with health conditions associated with great physical pain. Such apps can also be incredibly useful for pain specialists, who can use them to monitor highly detailed reports on patients’ pain thresholds, mood, physical activity levels and more.

Harvard PhD and Professor of anaesthesia and psychiatry, Robert Jamison, recently presented his research into smartphone apps for pain to the American Pain Society. His research found that existing therapies in this new domain could help control pain, improve the functional abilities of patients and also lower health care costs.

In those who feel isolated due to their pain or conditions, the apps can help to limit withdrawal, Jamison found. Smartphone data can also be summarized and converted directly into electronically kept patient notes.

Some currently available apps such as WebMD Pain Coach and MMP Lite focus on the tracking, analysing and communicating about pain. They offer data correlation and cloud storage facilities. There’s another interesting app, Mindfulness Meditation for Pain Relief, which offers a course of meditation programmes designed to actually lower pain perception.

A cutting-edge technological research project into pain relief is being conducted by entrepreneur Christopher deCharms, in collaboration with Stanford and Harvard Universities. In studies using $3 million MRI machines and virtual reality goggles, the team have been showing sufferers of chronic pain 3D models and representations of their own brains in real time in order to help them learn techniques for controlling their own brain states.

Based on this research, deCharms believes that it is possible to learn to activate various regions of the brain through such direct observation. The average improvement in clinical trials has been a 30% lowering of pain intensity: a huge result.

What’s even more amazing is that by modelling the best methods discovered for controlling one’s own brain regions in the MRI scanner, and building guided practices based on these, the researchers have achieved similar reductions in pain in users nowhere near the MRI scanner, but working from home on a smartphone, simply following the guided practices.

It is these (far more affordable!) models and guides which the project, known as Brainful, hopes to use to take the benefits to the mainstream. deCharms and collaborators have published several academic papers on their current findings, which make for compelling reading.

With both neuroscience, and the uniting of mind and brain studies still in their infancy, this technology has the potential to totally transform the medical norms we live with, and offer a real alternative to drug-based pain relief.


deCharms, R., Maeda, F., Glover, G., Ludlow, D., Pauly, J., Soneji, D., Gabrieli, J., & Mackey, S. (2005). Control over brain activation and pain learned by using real-time functional MRI Proceedings of the National Academy of Sciences, 102 (51), 18626-18631 DOI: 10.1073/pnas.0505210102

Image via pcruciatti / Shutterstock.

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Mapping the Human Brain To “See” What Makes You Unique Wed, 04 Mar 2015 01:52:02 +0000 The Matrix may not be fantasy anymore. The virtual reality shown in Avatar could be with us any time now, and at the same time, scientists are getting closer to decoding what goes on inside our brains. In fact, they are well on their way to mapping the human brain.

This means that you could really peek into the brain and “see” how it works for yourself — the domino effect of memory cells firing up to take you back to your childhood home and its smell of freshly-baked bread, or the flurry of activity in the learning center as you try to pick up the notes and play them on the piano.

Scientists have long known that the structural connectivity of the brain influences the functional performance of individuals. In other words, given the structural similarities of the human brain, it is the neural and synaptic connections within our brains that make us the unique individuals that we are. But what they want to do now is to create a complete map of the brain to discover how memories are stored, how personality traits develop, and how people learn skills. It looks as if they are well on their way.

Enter the connectome!

Mapping the Connectome

The network of connections in the brain — up to 10,000 for each of the 85 billion cells — is known as the “connectome.”

It is a complex but organized system of wires unique to every person. Scientists believe that wiring faults hamper the way cells connect and signal to each other. This may lead to mental disorders such as depression, schizophrenia and learning disabilities.

So, scientists need a comprehensive model that not only shows the neuronal structures but also details the connections — how your brain figures out the moves when you play Diablo; how do you remember, recall, and apply knowledge; how do you sense changes in temperature and color.

The human brain comprises structurally distinct but functionally interdependent components. Scientists have to mine data at the neuronal level (microscale) where there are connections between individual cells, as well as connections between several groups of neurons (mesoscale), and at the regional level (macroscale), where different structures of the brain interact with one another. Combining the findings from these disparate sets of data will ultimately help scientists create a comprehensive map of the brain.

There have been quite a few connectome studies aimed at creating such mental maps.

How the Eye Detects Motion

One connectome study has decoded how the human eyes sense motion. It is interesting to note that neurological data for the study was gleaned from more than 2,000 volunteers who took part in an online game, EyeWire. The results of the study busted the myth, long held in visual neuroscience circles, that we see with the brain. Scientists now know for sure that visual stimuli is first processed (somewhat) by cells in the retina before being transmitted to the brain.

The photoreceptor cells in the eye capture light, but on their own they are not capable of sensing motion. They are connected to the starburst amacrine cells that are in turn connected to the optic nerve that transmits signals to the brain to be interpreted. The photoreceptor cells are connected to the amacrine cells in such a way that the visual stimulus hits the latter at different times, or with a time lag. The brain interprets the delay in receiving the signals as coming from a moving object.

The findings from the above study represent a step in the right direction for scientists engaged in finding ways to map the brain. The task is not easy because deciphering neuronal characteristics and behavior demands that researchers study a large number of neurons, ideally individually, in different areas of the brain. Scientists expect that continual advances in micro-electrode technology will enable them to target the teeny-weeny neurons. They also believe that the way computational technology is progressing, they will soon be able to process the data mined from the billions of cells and the almost countless neural pathways effectively enough to create a map of the whole brain.

Implications of Brain Mapping Studies

Scientists, physicians, psychiatrists, and the common man on the street have much to be excited about the brain-mapping studies that are currently underway. The implications are wide-ranging.

As already mentioned, neuroscientists believe that many psychiatric disorders are caused by faulty wiring in the brain. Being able to pinpoint where the connection has gone awry can help them explore effective therapeutic methods. Brain-mapping studies also hold promise for people who have suffered traumatic brain injuries.

Knowing how neural structures and behavior influence function can also help scientists understand the basis of cognitive processes. Their conclusions can help educationalists devise curriculum that best meets the learning needs and preferences of specific groups of students or those who are suffering from learning disabilities.

The findings from such brain-mapping studies are already being utilized to explore the scope of neural prosthetics. These findings will enrich the brain-computer interface (BCI) studies that are currently underway. Right now, scientists are at work to devise sophisticated, powerful, and sensitive BCI systems that can capture and process neural data in real time and use this to control specific areas of the brain. These BCI systems can forge an artificial connection, which should mimic a neural pathway, between a set of implantable electrodes embedded within a prosthetic limb and the brain. Such BCI systems have already been tested on monkeys, and it is not hard to fathom how eagerly amputees or those who are paralyzed are awaiting developments in this field!

In fact, scientists around the world are already excited by the advances made in neuromorphic computing. Researchers have developed a computer chip that simulates the brain and can replicate synaptic connections. They believe that when this device integrates data from more comprehensive brain maps, it will become powerful enough to help blind people move around physically with ease.

Brain-mapping studies are the latest buzz in the medical fraternity. The brain may not have revealed all its secrets, but hopes run high.


Kim, J., Greene, M., Zlateski, A., Lee, K., Richardson, M., Turaga, S., Purcaro, M., Balkam, M., Robinson, A., Behabadi, B., Campos, M., Denk, W., & Seung, H. (2014). Space–time wiring specificity supports direction selectivity in the retina Nature, 509 (7500), 331-336 DOI: 10.1038/nature13240

Kipke, D., Shain, W., Buzsaki, G., Fetz, E., Henderson, J., Hetke, J., & Schalk, G. (2008). Advanced Neurotechnologies for Chronic Neural Interfaces: New Horizons and Clinical Opportunities Journal of Neuroscience, 28 (46), 11830-11838 DOI: 10.1523/JNEUROSCI.3879-08.2008

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Image via solarseven / Shutterstock.

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Brains Aren’t Fooled By Virtual Reality Tue, 24 Feb 2015 12:00:20 +0000 The scenes and the environments in World of Warcraft games appear so real that, for a moment, you forget you are staring at the screen. Technology has advanced so much that we can not only recreate reality but also engage with it. But however real the virtual may seem, the brain knows the difference! According to the recently published findings, the neurons in the brain react differently when they perceive a virtual environment than when they are in the real world.

The GPS Cells in Our Brains

The clue to the brain’s varied responses to different environments lies in the “GPS” or place cells. These neurons in the hippocampus create and control cognitive maps by taking input from the environment. They fire when a person is in a novel environment to create episodic memories that help us remember events (what) and place these events in their appropriate contexts of space (where) and time (when).

Place cells are critical for learning and memory. Incidentally, the hippocampus region is damaged in people with Alzheimer’s disease, schizophrenia, epilepsy, post-traumatic stress disorder or in those who have suffered strokes. Because their ability to learn and recall events, people, and objects is severely impaired, these people find it challenging to move about and around the world.

How Do GPS Cells Behave in Real and Virtual Environments?

The modus operandi of the space-mapping neurons in the hippocampus is not wholly clear, but scientists have deciphered that these cells form mental maps of environments by registering the position of different objects in an environment to calculate distances between them.

However, they believe that apart from the visual-spatial stimuli, the smells and sounds present in an environment also go into the creation of mental maps. This may be the reason why the place cells behave differently in real and virtual environments because the computer-simulated reality does not provide varied sensory stimuli.

Because human and rodent neurons are similar, scientists have carried out tests on the hippocampal cells of rats to arrive at the above conclusions. Here’s how all the findings add up.

According to a study published last year, a place cell in the hippocampus fires or “lights up” (as evident from scan images) whenever the rat is in a new environment. A real environment contains many different sensory cues including distal visual and self-motion cues. However, a virtual environment contains only distal visual and non-vestibular self-motion cues. Experiments on rats in these two environments showed that only 20 percent of the place cells in their brains got activated in a virtual environment compared to 45 percent when they were placed in a similar-looking but real world. This indicates that apart from behaving differently in real and virtual worlds, the brain creates more effective and comprehensive cognitive maps when it is fed with multi-sensory cues.

The above experiment sheds light on other interesting goings-on in the hippocampus in real and virtual environments.

When the rats were in the real world, their place cells fired every time they passed an object (a fixed landmark). This occurred consistently, and scientists realized that the neural place cells probably create mental maps by computing the distance between objects. But when the rats were in a virtual environment, not only fewer place cells in their brains fired but they acted randomly as well. In the experiment, the place cells were activated based on the movements or the relative positions of the rats. For instance, the cells lit up whenever the rats paced five steps back and forth, irrespective of the landmarks they perceived.

Another curious finding came out from a similar experiment. When the rats were made to navigate the real world, the activity within the place cells that fired in response to environmental stimuli correlated with the speed at which the animals moved. The faster the rats moved, the greater was the activity in these cells and vice versa. In the virtual environment, a screen showing video of the real world moved in tandem with the rats to give them the perception that they were actually moving as they do in the real world. But their hippocampal place cells showed steady, rhythmic activity irrespective of the speed at which the rats changed their relative positions. This discrepancy indicates the brain does not register stimuli accurately in a virtual environment.

Scientists believe that a cognitive map of a virtual world should be a function of the relation between specific motion paths and peripheral landmarks. But experiments have proved otherwise. This clearly suggests that the brain recognizes the gaps between the real world and the virtual reality our technologies create.

What Do Scientists Make of the Brain’s Different Performances in Real and Virtual Worlds?

The hippocampus is involved in spatial learning and related memory formation. The above experiments throw some light on how the brain works to create and retrieve memories. These findings bring hope that the mysteries of the hippocampus will one day be decoded and therapeutic procedures will be devised to enhance the quality of life of patients suffering from neurodegenerative disorders.

The above experiments also take some of the shine away from virtual reality technologies. For all the hype, it is obvious that the virtual is not as “real” as it is made out to be, at least as of yet.

Computers cannot recreate the “feel” of the real world — the smell of freshly-baked bread wafting through the air, the rustle of leaves in the breeze, and the crunching of gravels under the feet. Computer programmers and analysts may be concerned. After all, the closer virtual reality is to reality, the more accurate would be the performance of the critical job-related simulation applications used by military personnel, aviators, and scientists.


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Image via magicinfoto / Shutterstock.

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What Do Smartphones Do to the Brain? Sun, 22 Feb 2015 12:00:49 +0000 Even as the smartphone continues to evolve in functionality and power, parents are anxious that their kids seem to be addicted to their device. According to them, all that their kids do is switch off their ears, bury their heads, and tap, flick, and scroll on their touchphone screens. But, scientists have discovered at least one way in which the smartphone affects the brain positively.

There are as many people who see the smartphone as a pest and a distraction as there are people who hail the device as a marvel of technology. It is no wonder guardians are worried about the excessive use of smartphones. But not everything is as bad as it might look to some people.

Smartphone Usage Can Reorganize Brain Structure

According to a new study published this year, regular and heavy smartphone users exhibit increased activity in the cortical area of their brains in response to touch on their thumb, index, and middle fingers. Incidentally, the thumb and the index finger are those used most by smartphone users.

The researchers compared the results of this study with brain scan images of other individuals who used older makes of phones. The results of this comparative study showed that the fingers of the smartphone users were much more sensitive to touch (as demonstrated by the flurry of activity in the cortical region) than those of the non-smartphone users. What is more, the cortical activity increased proportional to phone usage. The study also found that the thumb showed the most sensitivity to smartphone usage.

In this context it is worth mentioning that the smartphone study found no evidence of a relationship between cortical structure and activity and the number of years the subject had been using a smartphone. It seems the brain starts to show changes, albeit subtle ones, after just weeks. The scientists believe that the findings of their study indicate that the brain has the ability to reshape and rewire itself influenced by daily activities, such as the use of personal digital technology.

Smartphone Users Exhibit Similar Neural Plasticity as Piano Players

The findings from the above study seem to corroborate the conclusions drawn from another piece of research conducted on musicians a decade ago. That study compared the level of tactile acuity in non-musicians and in professional pianists who had been practicing every day for long hours for many years. It was found that the musicians had greater degrees of tactile acuity than the non-musicians. Amongst the musicians, those who had been practicing more intensively through the years showed more sensitivity.

The study went a step further and subjected the pianists and the non-musicians to tactile co-activation. Tactile co-activation is a passive pulse stimulation protocol that is known to enhance activity in the somatosensory cortex or the region of the brain that responds to tactile stimuli. This brings about an improvement in tactile and spatial discrimination performances without the subjects going through a physical training and learning program. According to the findings of another study, the improvements in the performance are directly proportional to the increase in the primary and secondary somatosensory cortical areas of the brain.

Researchers found that after tactile co-activation, both the pianists and the non-musician groups exhibited improved tactile acuity. But the pianists exhibited a greater degree of improvement than the non-musicians. Again, the degree of gain in performance was positively correlated to the intensity of musical practice. These findings led the scientists to believe that the sensorimotor cortical structure and functionalities are essentially different in musicians than in non-musicians and that former’s brains are more adaptable making them better learners.

Repetitive Tasks and Finger Movements Can Stimulate the Brain

Training and learning through attention and reinforcement of stimuli can bring about changes in the cortical organization, which in turn, improves perceptual performance. Last year, a study was carried out on several stroke patients with varying degrees of sensory impairment and mild to severe motor deficit. They were made to undergo regular sensorimotor training sessions whether they had to explore, feel, and discriminate between textures, shapes, weights, temperatures, and objects with their hands. Brain scan images taken after the training period showed that both patients had experienced subtle neural reorganization.

A similar suggestion was made after another study was carried out on two groups of musicians who had received unimodal and multimodal training. It was demonstrated that sensorimotor-auditory training reorganizes the cortical region and makes it more flexible.

The findings of the above studies hold hope for stroke patients and other individuals who may have suffered brain injuries. Researchers, physicians, and physical therapists should look into devising physical rehabilitation programs that engage and exercise the hands of the patients in an effort to stimulate regions of their brains to reorganize and possibly restore the lost neural connections. Such therapy can enhance the quality of life of the patients.

The findings of several other studies also suggest that performing tasks repetitively with the fingers can increase cortical plasticity. One study cites the instance of Braille readers and musicians who perform on string instruments. The subjects in the study had been using their fingers to perform various tasks for many years. All of them exhibited excellent sensorimotor skills and enhanced activity in the cortical regions of their brains. The study also reported that extended periods of disuse, like when the arm was cast in a plaster and immobilized, resulted in decreased tactile acuity in the affected hand (as was evident from the deteriorating levels of perceptual performance) and decreased activity in the corresponding somatosensory cortical region.

So do these findings suggest that using smartphones can make you smarter? Although recent studies have found that heavy smartphone users have increased cortical activities, it is still quite early to confirm or negate a positive correlation between using a smartphone and scoring straight A’s in college. So smartphone addicts: you do not yet have the license to forego the company of friends and family members or forsake exercise in favor of your iPhone!


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Image via nenetus / Shutterstock.

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