“Man had always assumed that he was more intelligent than dolphins because he had achieved so much — the wheel, New York, wars and so on — whilst all the dolphins had ever done was muck about in the water having a good time. But conversely, the dolphins had always believed that they were far more intelligent than man — for precisely the same reasons….In fact there was only one species on the planet more intelligent than dolphins, and they spent a lot of their time in behavioural research laboratories running round inside wheels and conducting frighteningly elegant and subtle experiments on man. The fact that once again man completely misinterpreted this relationship was entirely according to these creatures’ plans.” – Douglas Adams, The Hitchhiker’s Guide to the Galaxy

As tempting as it may be to believe the science fiction version of the intelligence rankings, real-life science has spoken and suggests (much to my displeasure) that humans may actually be the highest on the intelligence scale.

Glia are non-neuronal cells found in the brain mainly described as performing “housekeeping” functions, for example, providing structural support to neurons, and providing them with nutrients. Astrocytes are a specific type of glia, and as one might hypothesize, they are bigger in humans than in mice. Was this just a consequence of humans having more complex brains, or do these astrocytes have different functions in humans beyond the basic housekeeping functions? To test this, scientists grafted human astrocyte progenitor cells into developing mouse brains to create chimeric mice.

Human astrocyte (green) and mouse astrocyte (red)

The human astrocytes that matured successfully matured as human cells; characteristics such as their size were unaffected by being in a mouse environment. But they did not remain completely foreign – they successfully formed electrical connections with the mouse cells. Their differing cellular properties were thus propagated into the mouse neural networks. Of particular interest is the hippocampus, the brain region important for learning and memory. Chimeric hippocampal slices had a higher level of baseline excitatory activity, and long-term potentiation (LTP), or synapse strengthening, was much greater. At the molecular level, this can be explained because the human cells express higher levels of a protein that promotes an increased number of glutamate receptors at the synapse.

There were also clear differences in the behavior of chimeric mice. Experiments were performed to test learning and memory abilities to corroborate the cellular results observed in the hippocampus. A classic fear conditioning experiment involves pairing a tone with a foot shock; mice learn to associate the two and exhibit freezing behavior after hearing a tone. Chimeras learned the association after only one tone/shock pairing. The learning persisted for several days, during which time control animals did not learn the initial association. The experiment was repeated as context fear conditioning, meaning that the mice were placed in different chambers that had varying floors and odors. Chimeric mice were able to differentiate between chambers significantly better than their control counterparts. In other learning and memory tasks, these mice learned their way through mazes faster and were better at familiar object recognition in novel contexts.

The results of this study show that glial cells have much more function beyond their basic housekeeping properties. A single cell graft manipulation was enough to significantly improve mouse performance on learning and memory tasks. Complexity of these cells has evolved with the brain, and this provides important new insight on how exactly this complexity has come to be. Future experiments could involve grafting chimpanzee or macaque glia, any differences observed could be key in outlining how our processing abilities evolved from our monkey fathers (I additionally support research with dolphin glia grafts, keeping on the theme of the three most intelligent species). Unfortunately, without the higher processing abilities made possible by human cells, mice likely cannot achieve the tasks and level of status they exhibit in the science fiction. It seems as though man has indeed correctly interpreted his relationship with the mouse.

So long, and thanks for all the fish.

-Reena Clements

References:

Human Brain Cells Boost Mouse Memory – ScienceNOW

Forebrain Engraftment by Human Glial Progenitor Cells Enhances Synaptic Plasticity and Learning in Adult Mice – Cell Stem Cell

We have many different types of neurons within our peripheral somatosensory system. In addition to basic mechanoreceptors, we have neurons corresponding to pain sensations, and channels that are temperature sensitive. However, one phenomenon that was not explained at the neuronal level until recently, is the sensation of stroking. On the behavioral level, we know that stroking or grooming is pleasurable in such phenomenon as maternal care. But how is this transduced at the molecular level?

Researchers in David Anderson’s lab at Caltech recently discovered a class of neurons that selectively responds to “massage-like” stimulations. Experiments were performed in-vivo to directly measure the effect of certain stimulations. Calcium imaging, a type of imaging designed to study activity of neurons, was used in the spinal cord, where the cell bodies of neurons projecting to the periphery are located. After mice were pinched, poked, and light-touch stroked on their paws, the researchers found that a subset of neurons was selectively activated to only the light-touch stimulus.

Mouse being stroked (Discover Magazine and David Anderson Lab)

To help support the results behaviorally, mice were given a two-choice test between a chamber where they received a drug activating the light-touch neurons, or a chamber where they received a control saline solution. Mice preferred the chamber with the drug that activated the light-touch neurons, suggesting that the animals form a positive association with having these neurons activated.

While similar neurons are thought to exist in humans, more studies need to be done on the nature of the potential light-touch fibers. These studies, when paired with behavioral data, can also provide insight into the biological basis of stroking and grooming in behaviors such as maternal care or social bonding experiences. Perhaps the reasons for this innate behavior (who ever thought of hugs as a feel-good mechanism, anyway?) actually has a stronger molecular link than we initially thought.

And to tie in this study with internet culture, here’s a recap video:

Sources:

Genetic identification of C fibres that detect massage-like stroking of hairy skin in vivo – Nature

We live in an era where the rapid advances in technology are constantly changing how we perceive and interact with the world around us. The question on everyone’s mind is always “what’s next?” The answer: brain-machine interfaces. For the average consumer, brain-computer interfaces are becoming increasingly available on the mass market and their current uses offer a wide range of fascinating opportunities.

A company that’s been in the news a lot lately is NeuroVigil. Their product known as the iBrain has been used to help world-renowned astrophysicist Steven Hawking communicate with a computer simply by thinking. Hawking, who suffers from Lou Gehrig’s disease, developed his own solution to allow him to speak by twitching his cheek to select words from a computer. In its current state, the iBrain is still slower than Hawking’s solution, but NeuroVigil’s founder MD Philip Low hopes that it will eventually be possible to read thoughts aloud. NeuroVigil also made the news by signing a contract with Roche, a major Swiss pharmaceutical company, to use the iBrain in clinical studies for evaluating drugs for neurological diseases.

Philip Low with the iBrain

So how does the iBrain actually work? The iBrain uses one sensor to measure brain signals by means of specialized algorithms. Surprisingly easy to use, NeuroVigil claims that its software makes up for using only one channel. A competing device, the EPOC, made by Emotiv uses a multitude of sensors. The EPOC is a neuro-headset that looks like headphones with sensors extending in all directions. These sensors pick up electrical signals that our brains produce while we are awake or asleep; essentially an EEG recorder. These measurements are not accurate enough to pick up what individual neurons in our brain are doing, but they can provide a rough idea of overall brain activity. Users of the headset learn to think specific thoughts for which the EPOC learns the related brain signals corresponding to a certain command, such as moving the mouse to the left. Emotive has an online store with dozens of applications for the headset and there is also a Mind Workstation for research purposes.

Emotiv's headset

The key strategy of another company, Zeo, is sleep research. Zeo offers a wireless headband to monitor sleep patterns that connect to smartphones using a Bluetooth link. Looking to enter the research scene with their innovative technology at a bargain price, Zeo hopes that it can satisfy the huge demand for a sleep aid product. In a similar manner, NeuroVigil wants to use a smartphone processor to map people’s mind while they sleep using the unique brain ‘signatures’ to diagnose neurological disorders such as Alzheimer’s, depression and autism, which again increases the number of potential users. An increasing number of people want to do their own health monitoring and new, inexpensive, wireless sensors and data processing by smartphone apps can help in this goal. Cheap brain-computer interfaces are the next step in this health-monitoring trend and will hopefully lead to newer and much cooler extensions of our mind.

Zeo headset and its app

Sources:

Emotiv

NeuroVigil

Zeo Sleep Manager

There are numerous brain imaging techniques that allow us to gain insight into what damage the brain may have incurred after a patient has a traumatic injury. The ever popular fMRI measures blood flow to infer neural activity. Diffusion tensor imaging (DTI) uses the magnetic properties of water to look at white matter in the brain, while positron emission tomography (PET) uses radiolabeling to look for a specific chemical in the brain. All of these are important for possible disease diagnosis, however, there is skepticism around how dependent we should be on this technology, as the results should never be taken as the absolute truth.

Comparison of X-Ray to HDFT

Now, a new type of brain imaging developed by researchers at the University of Pittsburgh allows researchers to look for connections that have been broken as a result of traumatic brain injury, much like an X-Ray allows doctors to look for broken bones. It is called High Definition Fiber Tracking (HDFT). Although the technology is not specific at the cellular level, it is accurate in observing specific connections that have been lost as a result of injury. These lost connections act as a reliable predictor for  cellular information, such as the percentage of axons that have been lost.

The accompanying publication in the Journal of Neurosurgery focuses on a case study of a man who sustained severe brain damage after crashing an all-terrain vehicle (public service announcement: this is why we wear helments!!!). Initial MRI scans showed hemorrhaging in the right basal ganglia, which was confirmed by a later DTI. The patient  had extreme difficulty moving the left side of his body, and it was assumed to be a result of damage to the basal ganglia. It was not until the patient had a HDFT test that doctors could pinpoint the true problem: fiber tracts innervating the motor cortex had been lost.

Above is a comparison of the techniques that the researchers saw. The first column consists of scans from a normal patient, while the second two columns are the brain injury patient 4 and 10 months post injury. The imaging techniques used are MRI, DTI, and HDFT. The HDFT gives a clearer picture of what specific connections in the brain have been lost.

The following image comparing DTI with HDFT also shows the inaccuracies of the older technologies.

In healthy subjects, the DTI shows connections and fiber tracks which do not correspond with what we know about brain anatomy, including false turns (deviations from the pathway), false continuations (midline crossing), and looping (travel in random directions). The HDFT scan is consistent with brain anatomy. Thus, the use of HDFT was essential in pinpointing exactly what connections had been lost as a result of the patient’s traumatic brain injury (see Figs 5 and 6 in accompanying paper, linked below).

HDFT has the potential to become the future of diagnoses in patients who have sustained traumatic brain injury, thus revolutionizing how we can treat these patients.

The following video shows a summary of the new technology in addition to the patient in the research paper’s case study:

New Brain Imaging Technique Reveals Damage Caused by TBI … -YouTube

Further videos and news releases are available on the HDFT lab website, linked below.

References:

Concept | HDFT – High Definition Fiber Tracking – HDFT

High-definition fiber tracking for assessment of neurological deficit in a case of traumatic brain injury: finding, visualizing, and interpreting small sites of damage. – Journal of Neurosurgery

New High Definition Fiber Tracking Reveals Damage Caused by Traumatic Brain Injury -University of Pittsburgh Medical Center

What kind of day would you rather have?

A decision is a fact of life. Both the good and the bad, the wrong and the right, one seemingly unjust turn waiting to happen amid the uncertain crossroads of life. Lets be honest, making a decision will always provide the answer, that is the ideal outcome, nothing goes wrong, everything is perfect, happily ever after. On the contrary, there is the undesirable result, which you would rather keep trapped in a cage and have thrown into a river in order to prevent ‘it’ from ruining your party. Now with making a decision comes the possibility for his arch-nemesis “regret” to appear in the equation. Lets look at it this way, if your friend ‘decision’ calls and asks if you want to see this movie which you assume is going to be terrible, you’d probably say “No,” thereby rejecting ‘decision.’ A week later ‘regret’ sends you a letter saying ‘decision’ went to the movie that day, saw your partner, they both hit it off, ‘decision’ slept with them, and now your partner never wants to see you again. See why you should have gone to the movie! That my friends is exactly, to a tee, the comic strip you will see when you look up decision in the dictionary.

Long ramble short, the art of making a decision occurs too many times to count each and every day. Should I hit the snooze button once or twice? How will this effect the amount of time it takes me to get swagged out? If I don’t proceed with the normal swag process, will my 8 a.m. classmates think any less of me than they already do? Who knows, but that is why we are here, right? Yes. For I am the storyteller, the sandman who makes you sleep so soundly at night, and the keeper of the secrets as to why you may or may not be indecisive. So without further adieu, hop on the magic school bus children as we begin our journey to the…(suspense)….build up…bum bum buh…the LAND BEFORE TIME!!! Well maybe, but in the meantime, lets take a look at how Neuroscientists have caught a glimpse of how the brain decides what to believe.

Everyday struggles can be life-threatening

A sense of what we know and don’t know is a universal human experience often associated with how confident we are with the decisions we make. Ultimately, the more confident we are with a decision, the more difficulty we may have breaking away from that choice. However, new research being completed by Neuroscientists at Cold Spring Harbor Laboratory suggests that the estimation of confidence that underlies these daily decisions may be a product of information processing within the brain. To solve this ongoing debate, researchers began trials using rats and their heightened olfactory senses to test their levels of uncertainty. Translated to English, scientists knew that rats sense of smell is extremely sensitive. With this knowledge, they produced mixtures containing varying strengths of smells and gave rewards to the rats who were able to distinguish which component of the mixture was stronger within that specific mixture. In essence, if a rat is able to relay back to a scientist that there was more snozberry than b-a-n-a-n-a-s in the mixture, he or she was given an incredibly delicious reward.

While undergoing these trials, scientists recorded signals from individual neurons in the rodents’ brains. They found that neurons in a part of the brain known as the orbitofrontal cortex (an area of the brain found in both rats and humans) signal the uncertainty of the decisions, “firing” much more vigorously in difficult tests compared with easier tests. Coupled with a follow-up study that was designed specifically to test the confidence of the rats, scientists were able to learn further information pertaining to the neuronal sequences that correlated with confidence. Unlike the first study, in which the rats were given a reward immediately should their decision be correct, this study created a significant delay period between the end of the trial and reward. During this period of time, the rats were given the option to abort the trial and begin again, prior to learning the fate of their decisions. Ultimately, rats often chose to abort the current trial, depicting how they could not only calculate their levels of confidence with their decisions, but translate that response into behavior. Pretty cool huh?

So what have we learned today. Rats may be able to distinguish between various smells, but can they spell b-a-n-a-n-a? Confidence in relation to decision making is not a complex process only associated with humans, but rather a core component of decision making that is found throughout the animal kingdom. And finally, there is always a right way to make the wrong decision and vice versa (Yeah, try and play that one out in your head) lol.

Confidence plays a role in Decision-making – Science Daily
Single Neurons – Science Daily

Research has been conducted that proves that our thoughts can control the rate of firing of neurons in our brain. This research reveals the crucial advancement of brain-operated machines in the field. John P. Donoghue at Brown University has conducted research that uses neural interface systems (NISs) to aid paraplegics. NISs allows people to control artificial limbs; individuals simply need to think about commanding their artificial limbs and signals are sent down from their brain to control the movement of these limbs! This great feat is not the only applicable result of current research done by brain-machine interfaces. Dr. Frank Guenther of Boston University uses implanted electrodes in a part of the brain that controls speech to tentatively give a voice back to those who have been struck mute by brain injuries. The signals produced from these electrodes are sent wirelessly to a machine that is able to synthesize and interpret these signals into speech. This is specifically useful for patients suffering from locked in syndrome, wherein an individual with a perfectly normal brain is unable to communicate due to specific brain damage, and thus allowing these individuals to communicate with the world! These discoveries are not only incredibly useful, but they also reveal the astonishing feats that the field of computational neuroscience is accomplishing in the world today.

On-line, voluntary control of human temporal lobe neurons

Guenther, Boston University

Donoghue, Brown University

Because of the brain’s amazing and incomprehensible complexity, there are billions of neurons that connect and network all the major areas of the brain with the small intricate parts as well. So how can we distinguish one of these neurons from the billions of others?

Well, within the past five years more advanced techniques have been discovered and used on various organisms. The most prevalent, and probably the most revolutionary, has been staining. This process was pioneered in the late nineteenth century by Camillo Golgi and allowed for the staining of whole, random cells.

Since then, much progress has been made and today the viewing of even more complex and minute parts that make up the brain is possible. One extraordinary technique was developed by a team of Harvard researchers a few years ago, and it is truly beautiful.

Known as the Brainbow technique, these investigators were able to use genetics to visualize complete neuronal circuits in unprecedented detail. Up to four differently colored fluorescent proteins were used, generating  a palette of 100 distinct hues that labeled individual neurons.

Here are the fluorescent proteins in their full glory illuminating the many neurons that make up the brain of a mouse.

This technique was developed with the use of the Cre/loxP site-specific recombination system, a sophisticated method that is commonly used to generate mutant mice lacking a specific gene. Basically, this recombination inverts parts of the DNA sequence at specific sites along the genome. The mating of two different mice strands allows for recombination.

Fluorescent proteins were added to certain constructs of cells, all of which were able to emit colors such as red, cyan, yellow, and green. Multiple copies of the constructs were integrated into a stem cell chromosome, and many random combinations of these four genes were then expressed.

Confocal microscopy was used next to generate three-dimensional reconstructions that traced the multi-color palette onto complete neuronal circuits in various regions of the brain. Thanks to this incredible new technique, a large number of neurons and the connections between them have been labelled and led to new systems based on this discovery.

Since its discovery, the Brainbow technique has allowed for unprecedented visualization of neurons and neuronal circuit in many classic model animals, such as the fruit fly and mouse. Hopefully one day, techniques such as this will aide us in our attempt to untangle the interconnections of our own brains and allow us to further appreciate its beautiful intricacies.

The 100 Colours of the Brainbow: Neurophilosophy

Harvard Researchers Illuminate Connections Among Brain Cells in Technicolor -Popular Science

Transgenic Strategies for Combinatorial Expression of Fluorescent Proteins in the Nervous System: Article – Nature

Colorful Images to Help Illuminate the Brain – NYTimes.com