The technique operates on the idea lipids in the bilayer of a cell’s plasma membrane block visible light. This is why the brain is normally not transparent. Removing these lipids but still keeping the other parts of the cell and its environment intact would render the brain “see-through” and allow for much easier imaging of large pieces of brain tissue, if not the whole brain at once. This idea is carried out by taking the brain and infusing it with acrylamide, which binds proteins, nucleic acids and other molecules, then heating the tissue to form a mesh that holds the tissue together. The brain is then treated with SDS detergent to remove the light-blocking lipids resulting in a stable brain-hydrogel hybrid. From here the transparent tissue can be fluorescently labeled for certain cells and analyzed. Through the whole process there is less than 10% protein loss in the brain tissue compared to around 41% for other current methods. This is an amazing improvement!

Example of brain image produced by CLARITY from neurons in an intact mouse hippocampus. (http://med.stanford.edu/ism/2013/downloads/CLARITY/CLARITY_stained.jpg)

Until now it has been common practice to use histology to analyze brain tissue in a study. This method involves slicing a section of brain up into extremely small pieces and dying certain slices for various cells and molecules of interest. If a researcher wants any idea of the bigger picture he/she must reconstruct the brain from these small slices. With the CLARITY technique slicing the brain up is no longer necessary. Never before has it been so easy to view full brains, or sections of brain, down to the cellular and molecular level. It is now easy to follow the trajectory of a single neuron through the whole brain.

The development of this brain imaging method comes at a time when much money is being put into uncovering the complete biological workings of the human brain. President Obama has announced his BRAIN initiative and the US National Institute of Health is working on its Human Connectome Project. CLARITY has big potential use for these initiatives and as the technique is refined it seems that it will have a large role in uncovering more about the elusive question of how our brains really work.

For more information on CLARITY view this video on Nature’s website:

http://www.nature.com/news/see-through-brains-clarify-connections-1.12768

- J. Daniel Bireley

Sources:

Structural and molecular interrogation of intact biological systems – Nature

See Through Brains Clarify Connections – Nature

In the past 150 years it has been noted that the onset of depression is occurring at higher rates and at younger ages that ever before. This data could be the result of factors including an increase in patients coming forward to be diagnosed, improved diagnoses, or simply better record keeping. Whatever the reason, it is estimated that 15 to 20% of the population is experiencing symptoms of major depression at any given time, with a greater occurrence in women than in men. Many are affected by this disorder and a cure has yet to be found. But before we continue, a distinction must be made between major depression and “reactive depression” in which a person may feel depressive symptoms because of a single event like the loss of a loved one or a failure of some kind. Major depression is a prolonged state in which an individual may display a number of symptoms including depressed mood, loss of interest in most activity, change in body weight or appetite, changes in sleep patterns, psychomotor agitation or retardation, fatigue, difficulty concentrating, feelings of worthlessness or guilt, and suicidal thoughts. Depending on the severity of the depression a patient may display many, or only a few of these possible symptoms.

Research has yet to find a definitive neurological cause for depression and other affective disorders. Studies of fraternal and identical twins have attempted to determine the role of nature versus nurture on the matter and animal models of depression as well as human studies have been used to develop drugs and other treatments for depression. Through this work different hypotheses have developed about the neurochemical basis of depression. Some are convinced a monoamine imbalance is responsible while others say it is an issue with serotonin dysfunction. These hypotheses have led to the development of different treatment methods and the utilization of a few classes of drugs. Drug classes include monoamine oxidase inhibitors, tricyclics, and selective serotonin reuptake inhibitors (SSRIs) which all have slightly different mechanisms of action in the brain when treating depression. What is most interesting is that after all this research and development none of these drugs stand out as the best treatment for depression. They all tend to improve depressive symptoms anywhere from a week to a month after drug therapy begins, and they all carry different, sometimes nasty, side effects. The main reason for the current love affair with SSRIs in the medical world is that they carry the most favorable set of undesirable side effects, not that they treat depression best.

Enter ketamine. This compound has a street reputation as a club drug and is derived from phenylcyclidine (PCP), another drug known for its powerful and potentially dangerous psychological and addictive affects. Both drugs were originally developed as alternative analgesics (pain relievers) to drugs like barbiturates that had a higher risk of respiratory depression and subsequent death. PCP and ketamine did produce analgesia, just not in the way they were originally thought to do so. Patients report feelings of detachment from their own body and reality when under the influence of these drugs. They can’t feel pain because their minds are off in another reality, essentially too distracted to feel anything. At high doses PCP and ketamine have been shown to induce schizophrenic symptoms in humans, or worsen previously existing schizophrenia, and research on schizophrenia uses ketamine to bring about a schizophrenic state in animal test subjects. So how on earth can a drug like this have any useful therapeutic application?

http://drug-effects.us/what-is-ketamine

http://www.guardian.co.uk/society/2010/apr/02/drugs-ketamine-bladder-problems-incontinence

Researchers at Yale University and the National Institute of Mental Health have recently found that administering a low dose of ketamine to a patient affected by major depression has been able to lift the patient’s mood and subdue the depression for about a week at a time. It is an astounding find given the known effects of ketamine on the mind. One study reported that 70% of patients treated with ketamine experienced an improvement in mood. One of the best parts about the treatment is that it takes effect immediately, unlike the other antidepressants on the market, which can take up to a month to work. It has also proven effective even to patients who have been resistant to other treatments. Ketamine is already an FDA-approved analgesic, usually used in veterinary settings, so further studies of this compound are now being developed in humans.

The mechanism of action for this drug is not yet clear but it is known that ketamine and PCP are nonselective NMDA receptor antagonists. They affect the glutamate pathways within the brain and also seem to have the remarkable affect of strengthening and restoring synaptic connections. In the human model of depression where it is thought that symptoms are caused by atrophy of neurons in various brain areas, it makes sense that ketamine is an affective treatment because it encourages neuron regrowth and connection. This may be done through the production of brain derived neurotrophic factor (BDNF) or other molecules that influence neuron health and maintenance. More work must be done to determine how this unlikely drug accomplishes its therapeutic affects. There are still dangers associated with taking ketamine, especially if it only works for a week at a time to treat depression and repeated use has already been shown to produce schizophrenic symptoms in some. It is an amazing and surprising find and hopefully it leads to more improved treatments of affective disorders like depression.

- J. Daniel Bireley

Sources:

Ketamine Relieves Depression By Restoring Brain Connections – NPR

Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents - Trends in Neurosciences

Meyer, Jerrold S., and Linda F. Quenzer. Psychopharmacology: Drugs, the Brain, and Behavior. Sunderland: Sinauer Associates, 2005. Print.

It may be an age-old saying that makes most people groan whenever a friend or family member feels the need to say it, but there are actual psychological benefits that come from simply putting on a smile. Researchers have been examining this phenomenon for a few decades now and even though it is not a new age, 21st century discovery, it is nonetheless amazing and unexpected. One would intuitively assume that facial expressions are an external representation of what is going on inside the brain. Classically, facial expressions are considered to be influenced by mood and thought. It seems to be a one-way street in which the brain controls the face, but this is not the case.

Charles Darwin hypothesized that emotional facial expressions are an innate and universal human characteristic. A happy face is a happy face no matter where you are in the world. This theory has been thoroughly explored and psychologists have produced evidence that supports this century-old speculation. This is convenient in a way, because if facial expressions were specific to a geographic region, people would have to learn faces as if they were learning a new language. What a challenge that would be! But the more interesting aspect to these universal facial expressions is that the physical expression can directly influence one’s emotions.

Studies on this finding were approached in multiple ways. One study conducted at Clark University in Worcester, MA instructed patients to move certain parts of their face in various ways, such as raising the eyebrows or relaxing the mouth, and then reporting their emotions. (The patients were not told that the study had anything to do with emotion.) In another study performed by a group of German researchers, patients were told to clench a pen in their front teeth, creating a smile, or hold the pen in their protruding lips, creating a pout, and then report their emotional state. In these studies, patient’s emotions were consistent with the resulting facial expression. So, it can be inferred from these findings that making a happy face can help make you happy. It must be noted that changing facial expression is not a means of changing one’s whole state of mind. Certainly someone who is mourning cannot just put on a smile and instantly be cured of all sadness. It is not that simple. It is more realistic to think that facial expression can influence emotion, not directly change it. We would all be in for quite a roller coaster ride of emotion if the opposite were true, and a rapid change of facial expression was able to instantaneously change our moods.

If this finding is valid then there must be some physical explanation or neural substrate to explain it. Even though researchers observed this phenomenon decades ago, a full explanation is yet to be obtained. There are a number of hypotheses, though. Many incorporate the brain’s limbic system, and specifically the hypothalamus – areas of the brain known to control emotional processes. The hypothalamus plays a role in the autonomic nervous system (ANS), which is responsible for many subconscious functions of the peripheral nervous system such as breathing, heart rate, and body temperature. From a physiological standpoint, it is hypothesized that a change in facial expression is able to change patterns of blood flow to limbic structures, therefore influencing one’s emotional state. There are researchers both supporting and refuting this theory, and a more concrete explanation is yet to be found. But the fact remains, put on a smile and your day may get a little brighter.

Sources:

A Feel-Good Theory: A Smile Affects Mood – NY Times

Facial expressions and the regulation of emotions – Journal of Personality and Social Psychology

Facial Expression and Emotion - American Psychologist

Social interaction and communication are essential characteristics of the human experience. As humans, we desire to create and develop relationships with each other. Autism Spectrum Disorder (ASD) is a neurological developmental condition that impairs this ability to relate. The spectrum refers to the fact that there are multiple conditions characterized by similar features all grouped together under this one disorder. These conditions include “classic” autism, Asperger syndrome, and Pervasive Developmental Disorder Not Otherwise Specified. There are also varying degrees of severity associated with ASD. So, depending on the disorder and degree to which a person suffers from this disorder, there is truly a wide spectrum of possible conditions created by ASD that many people around the world must deal with.

Autism is usually detectable within the first three years of life due to observation of cognitive symptoms common to most forms of the disorder. Biologically, researchers have found that autistic children often have enlarged cerebral and cerebellar volumes. There has also been some connection with ASD and certain chromosome variations. Autism is most commonly diagnosed through cognitive evaluation, though. The three symptoms that are noted most often are trouble with communication, issues involving reciprocal social interaction, and stereotyped behaviors such as obsession over specific interests and repetition of certain words or actions. Many severely autistic children do not develop speech and, if they do, it occurs at a significantly later time than a child without ASD. Eye contact is rarely made, emotions are not expressed, and there is a noticeable difficulty in understanding other’s feelings and thoughts. Any combination of these symptoms challenges a child’s development and many families are left trying to find an effective way to help their children learn and grow.

This is where the Ipad enters. Steve Jobs has invented some amazing technology. But it is even more impressive when this technology is able to help a child express feelings, words and ideas when this would otherwise be impossible. According to the Center for Disease Control, today 1 in 88 U.S. children in diagnosed with ASD. This is a 78 percent increase from data collected a decade ago. These numbers are astounding. The reason for such an increase is still being explored. Possible explanations include better diagnosis techniques or just a general increase in the number of people born with ASD. With such a high occurrence of autism in the United States and no known cure, more families are exploring different ways of assisting their children. With its sleek appearance and massive number of “apps” the Ipad has become one of these ways to help. In October of 2011 60 Minutes aired a segment about the potential use of the Ipad for teaching autistic children and providing them with a “voice.” I recommend viewing the piece below:

iPad and Autism Feature on 60 Minutes

Sources:

The Upside of Autism – The Wall Street Journal

Brain Abnormalities in Autism – American Academy of Neurology

About Autism – NIH

Some Genetics of Autism – American Journal of Human Genetics

In the United States alone there are about a quarter of a million people affected by spinal cord injury with over 10,000 new injuries resulting in conditions such as paraplegia and quadriplegia each year. Spinal cord injuries can be completely debilitating and can occur when least expected. Drawing from a high school memory of mine, a hockey player from a town nearby was pushed head first into the boards one night during a game and sustained a severe neck injury, permanently impairing his motor skills and changing the course of his life.

It is sad to hear about from a personal perspective but there may be new hope for recovery for people affected by these life-altering injuries. It may not be realistic yet to restore full limb use to a quadriplegic patient, but what if there are ways to make entire new limbs? I am not talking about the average prosthetic limb, but one that could move on command, through a patient’s thoughts. It used to be the talk of science fiction to imagine the mind moving objects just by thought. Now this idea is not so far-fetched. Through recent work in computational and cognitive neuroscience great strides are currently being made in utilizing the electrical activity of the brain non-invasively through a brain-machine interface (BMI) to control semi-autonomous robots that can do anything from picking up a cup of coffee to checking your email.

It is clear that the potential of this research is enormous, ranging from medical use to military use. The exact mechanism of how one can simply think about a motor task and have a robot perform that task is fascinating. The current research primarily takes advantage of the electrical activity that occurs within neurons during normal brain function. Through the use of electroencephalography (EEG), the voltage changes that arise due to movement of ionic current within neurons in a specific area of the brain can be measured. Electrodes attached to the scalp take these measurements non-invasively. With good temporal resolution and decent spatial resolution, the EEG recordings can be taken from an area such as the motor cortex, which lies conveniently in the frontal lobe of the cerebral cortex anterior to the precentral gyrus, and run through algorithms that decode the neural activity. In this way the electrical activity is turned into commands that the robot or prosthetic limb can carry out without the patient having to move a muscle. Besides EEG, researchers are also exploring the use of other methods of measuring neural output such as electrocorticographic signals (ECoG) and local field potentials (LFPs), which vary in their ability to measure electrical activity spatially and temporally. Depending on the exact goal of the brain-machine interface and the specific needs of the patient it may be more appropriate for measurements to be taken only from a precise area of the cortical homunculus, or for many commands to be decoded over a short period of time. These needs beckon the use of recording methods that are able to extract neural activity from precise groups of neurons over a given time period.

This research is currently happening right here at Boston University in the Neuromorphics Laboratory and center for computational neuroscience. Neuromorphics literally means a technology with a form based on the architecture of the brain. In this lab, founded in 2010 by Dr. Massimiliano Versace, Ph.D., the overarching goal is to model whole-brain systems and implement them at the biological level utilizing innovative neural chips and mobile robotic platforms. In this way the mind (whole-brain systems), brain (neural chip), and body (robot) are run in unison to create an intelligent agent that can perform motor and cognitive tasks that include learning and memory. One of the more amazing aspects of this lab work is that the algorithms they develop to decode the neural activity employ a two-way co-adaption paradigm that allows the patient and the prosthetic limb or robot to learn from one another. As movements are practiced, both the subject and the robot are able to improve their performance. These brain-machine interfaces are being tested continually with different kinds of robots and the BU Neuromorphics lab has already gained publicity for its work on this cutting edge technology, being featured in BU Today just last week.

Brain-machine interface research is still in its beginning stages. Eventually, it will not just be motor activity that is being recorded and decoded by robots. Hopefully there will someday be fully autonomous robots that perform tasks like aiding the elderly and robotic exoskeletons for those affected by spinal cord injury who wish to walk again. The possibilities for this technology grow as our understanding of brain function expands. To be able to provide a quadriplegic with the possibility of regaining at least some basic motor function is extremely exciting and this is exactly where BMI research will soon take us.

Here is a clip of a monkey utilizing a robotic arm connected to electrodes that record the activity in the monkey’s motor cortex to snack on a few marshmallows:

Spinal Cord Injury Facts and Statistics – SCI Info Pages

Building robots that learn – Aisha Sohail, CNN.com

Brain-Robot Interation – BU Neuromorphics Laboratory

Selecting the signals for a brain-machine interface – Current Opinion in Neurobiology

Toward electrocorticographic control of a dextrous upper limb prosthesis: building brain-machine interfaces.

- IEEE Pulse

Art is popular. There are many people that enjoy, support, or make a living off of art. It has the power to evoke emotion and also to allow one to express emotion through shapes, color, and patterns. Brains are popular too, but in a different sense. Everyone has a brain. Some may use it more than others, but it is something that all humans possess.  This is, of course, excluding the various other life forms on earth that  make use of a brain. What is not so popular is brain art. Especially brain art that is anatomically correct. The Museum of Scientifically Accurate Fabric Brain Art claims to be the largest collection of anatomically accurate representations of the brain made entirely from fabric. How exciting! The inspiration for each piece comes from dissections of the brain, functional magnetic resonance imaging (fMRI), neuroscience research, and positron emission tomography or PET (another medical imaging technique). These self-deemed “neuroartists” employ traditional art techniques such as quilting, knitting, and rug hooking to create their cranial masterpieces. Although extremely talented, these artists do warn not to use the accuracy of their art as a guide for any kind of surgical medical endeavor.

Check out one of the pieces:

"The Knitted Brain" by Karen Norberg

Check out some more of the collection here:

The Museum of Scientifically Accurate Brain Art

What comes to mind when you think of Friday? Friends. A night off from work. Movies. Fun. Rebecca Black? Yikes. I don’t mean to remind you of such a low point in the history of American pop-culture but there is, in fact, a small amount of useful information to be extracted from the phenomenon that is Rebecca Black. Why did her music spread like an epidemic through the minds of millions of teens and adults worldwide? This event can be loosely related to what the Germans like to call an öhrwurm.

The term öhrwurm literally translates in English to “earworm”, and can be described as that inescapable occurrence of getting a song stuck in your head for an hour, a day, or even months at a time. The term is misleading in that the repetition of music does not occur in the ear but within the brain. For an experience that is so familiar to most people there is still much unknown as to how and why one contracts this stuck song syndrome.

One man that has put some time into the issue is Professor James Kellaris of the University of Cincinnati. He coined the term “cognitive itch” to describe his theory of the instance of getting a song stuck in one’s head because the only way to satisfy the feeling is to repeat the song over and over inside the mind (kind of like scratching an itch). He has found that there are certain kinds of music and songs that tend to induce an unusual reaction in the auditory cortex. This extra attention that is paid to a small part of a song produces the “itch”, which then starts the vicious cycle of repetition. Simple songs that are catchy and repetitive are found to be the one’s most often plaguing the mind, as well as songs with unpredicted rhythm changes. This is why “Don’t Stop Believin’” or “Hey Jude” will continue to live on decades after their original heyday in American culture.

Research so far has been unable to uncover the exact biological mechanisms of this phenomenon. A recent study done at Dartmouth University, however, has shed some light on not only how the auditory cortex (the area where the brain processes most of the external auditory stimuli it receives) may be involved in producing this odd effect, but also on some other areas of the brain and how they are involved in producing the “earworm” as well. Using magnetic resonance imaging techniques it was found that when a patient is exposed to a catchy tune with some parts of the song missing here and there, the auditory cortex does not just shut down or anything during these silent gaps. In fact, if the song is recognizable the brain will fill in the missing pieces and effectively continue the song even when it is not playing! The brain’s ability to retain auditory signatures makes it possible for us to preserve “many structural and temporal properties of auditory stimuli” such as songs. This discovery indicates that the auditory cortices of the brain are most likely involved in the occurrence of earworms. Besides the primary and secondary auditory cortices though, blood flow has been found to increase in such other areas as the primary motor cortex, frontal operculum, insula, posterior cerebellum, and basal ganglia when the brain is exposed to “novel melody” or monotonic vocalization. When a repeated melody is heard, there is also additional stimulation in the planum polare (BA 38). Further study of these brain regions has the potential to reveal more about not just the mystery behind earworms, but also about the complex memory systems of the mind.

It has also been shown that there are people who are more prone to earworms than others based on gender, physical characteristics, and personality. For example, women are more likely to be affected by a stuck song for a longer period of time than men. Supposedly left-handed people and people with anxiety disorders like OCD are more likely to catch an earworm, and so are people who are more musically inclined (most likely because they listen to more music than the average person). So if you are a left-handed, obsessive compulsive female musician and just can’t get rid of that annoying background music that’s been in your head all day, try a few of these tactics: turn on the radio, play a different song for yourself (on one of the many instruments you have at hand), listen to that song, or try to pass the misery along to someone else.

The “earworm” phenomenon, and the ability for a simple melody to last months, or even years inside the mind is just another one of the many fascinating aspects of the brain. Because of this ability, I am stuck here with Britney Spears on replay in my head at the moment. But, hey, at least it’s not “Friday.”

And in case you don’t have an earworm of your own here is a video that will give you a few (and maybe a laugh too…)

Earworms (stuck song syndrome): Towards a Natural History of Intrusive Thoughts – British Journal of Psychology

The Song System of The Human Brain – Cognitive Brain Research

Why Do Songs Get Stuck in Your Head? – Word Detective

Science of Music – Exploratorium

Why Do Songs Get Stuck in Your Head? – The Straight Dope