The year is 1966. After months of extensive preparation and creative troubleshooting, three scientists studying the brain’s unique split personality eagerly awaited the results of their carefully designed experiment. By placing an electrode into a cat’s corpus callosum, they were hoping to decode the brain’s elusive internal code. What they ended up finding was something much more profound, and much more revealing…

The corpus callosum is a thick bundle of neural fibers connecting the two sides of the brain. As the largest white matter structure, it allows the brain to communicate interhemispherically, and because of this, has been implicated in several brain disorders. On one side of the spectrum, you have epilepsy. The symptoms of this chronic neurological disorder are amplified by the hemispheres’ ability to communicate, because the neuronal hyperactivity starts on one side of the brain and then spreads to the other. In severe epilepsy resistant to treatment, this is sometimes surgically mediated by a corpus callosotomy in order to sever the communication pathway.

This procedure leads to split-brain, a condition resulting from the lack of communication between the two sides of the brain. This creates an interesting dichotomy, no pun intended. Since the information that enters the left visual field is shuttled to the right side of the brain and vice versa, the lack of communication makes things a little difficult. For example, because the speech-control center is on the left side of the brain, the patient is unable to name an image seen through the left visual field and analyzed in the right hemisphere. For those of us who have seen the House episode involving the patient with a split-brain (disregarding the typical improbable ending), it was pretty awesome to see split-brain in action. And yes. I realize that it’s just TV.

This idea proved extremely interesting to Dr. Michael Gazzaniga, currently featured in The New York Times’ Profiles in Science. A professor of psychology at UC Santa Barbara and champion of early split-brain research, a young Gazzaniga was inescapably drawn to neuroscience after a spontaneous summer internship at Caltech in the lab of Dr. Roger Sperry (who incidentally went on to win the 1981 Nobel Prize in Medicine for his split-brain research). Together, they designed a series of experiments to further understand this hemispheric specialization. The studies contained experiments demonstrating the capabilities of each side of the brain. In one, they came up with a way to show a picture of a bicycle to only the right hemisphere. Split-brain patients would always reply that they saw nothing. Even though the right hemisphere “saw” the bike, the severed connection left no ability to communicate the name of the object, as that ability lives in the left side of the brain. But, alas! The right hemisphere was able to direct the left hand to draw the bicycle. In another clever experiment, they showed that the right hemisphere could identify objects by touch.

The implications, now made perfectly clear to neuroscience majors, were incredibly important. They could now show that the left hemisphere was the “wordsmith” and the right hemisphere was the “artist”. They had effectively eliminated the theory that the brain was a uniform processing entity. For fun, next time you’re watching a movie or TV, take a look at how many famous actors are left-handed.

So let’s get back to these three brilliant scientists. One of them, coincidentally, was a Michael Gazzaniga. Expecting that a considerable scientific discovery was about to occur, they leaned forward to listen to the amplified whisper of the brain’s activity. Pop. Buzz. Silence. Then, “…we all live in a yellow submarine, a yellow submarine, a yellow submarine”. After a moment of incredulity followed quickly by the numbing understanding of their naiveté, they realized that the electrode had picked up the frequency of a local radio station. They weren’t listening to the brain’s secret code. They were listening to the Beatles’ most recent hit. Ok, so maybe what they found was neither revelatory nor ingenious, but it certainly makes for a funny story.

Telling the Story of the Brain\’s Cacophony of Competing Voices – NYTimes.com

Forty-five years of split-brain research and still going strong – Nature Reviews Neuroscience

Let's hope he doesn't show up in your dreams.

Since dreaming occurs while sleeping, it is no surprise that the sleep cycle, during which the brain experiences patterns of varying electrical activity, has been implicated in dream theories. Each cycle consists of five stages – two stages of light sleep, followed by two stages of deep sleep, and completed with a stage of rapid eye movement sleep (REM). Unfortunately, there is no representative electrical pattern associated with dreaming, but REM and non-REM sleep have both been connected to the brain’s analysis of waking experiences. Pierre Maquet at the University of Liege, Belgium, observed deep non-REM sleep and found that the brain’s electrical activity mimicked the electrical activity elicited during waking experiences.

Not only do we replay events in our dreams, but we also seem to process, integrate, and store the information for future use. Robert Stickgold of Harvard University found that those who had non-REM dreams about a task that they were asked to complete, proceeded to do better on it. Stickgold proposes that “non-REM dreaming might be more important for stabilizing and strengthening memories, while REM dreaming reorganizes the way a memory is stored in the brain, allowing you to compare and integrate a new experience with older ones”. On a different, albeit related note, daydreaming activates a part of the brain called the default network. This region has previously been shown to be associated with memory processing. Be sure to mention this to your professor next time you’re caught not paying attention in class.

Matt Walker of the University of California acknowledges that dreaming has an important role in memory, but argues that the main function is emotional homeostasis. Walker has found that REM sleep facilitates the strengthening of negative memories. He believes that experiencing the negative emotion in a dream state can diminish the intensity of the emotion, making it easier to deal with. In those with post-traumatic stress disorder, however, this process seems to fail. Boston University’s Patrick McNamara agrees with Walkers’ speculation. He believes that “non-REM dreams help us practice friendly encounters, while REM dreams help us to rehearse threats”.

While dreaming, the brain rewires itself and forms new connections. It seems that this curious kind of consciousness does not reveal our secret desires or open windows into our hidden selves, but instead plays an integral role in making us who we are. Sorry, Siggy.

To view the original article from New Scientist, click here!

In June 2010, Mauricio Vargas and colleagues from Stanford University School of Medicine reported research in Proceedings of the National Academy of Sciences showing that endogenous antibodies play an important role in repairing peripheral nervous system (PNS) damage. Antibodies are a principal part of the adaptive immune response to infection, but this research suggested that antibodies are also able to clear degenerating myelin which inhibits axon regeneration, akin to a homeostasis function. This repair was only present after PNS injury, whereas myelin debris remained in the central nervous system (CNS) white matter for years. The well known blood-brain barrier concurs with this separation in responses, as it is understood to be impermeable to large proteins such as antibodies.

Various new studies, however, have shown that behavior, mood, and memory can all be influenced by aspects of the immune system, suggesting that antibodies can somehow infiltrate the brain.

Sammy Maloney was a happy and outgoing 12-year-old boy. In 2002, however, his mother started to notice curious deviations in his personality. In six months, he underwent complete mental deterioration and was diagnosed with obsessive compulsive disorder and Tourette’s syndrome. Shortly afterwards, he was found to be harboring a streptococcal infection, although he exhibited no physical symptoms of one. Interestingly, when he started taking the prescribed antibiotics, his behavior markedly improved.

Madeline Cunningham at the University of Oklahoma has spent several years investigating various behavioral disorders associated with streptococcal infections. Cunningham has shown that antibodies against one group of streptococcal bacteria are able to bind to a site in the brain that controls movement, and consequently trigger the release of dopamine. This could explain the emotional disturbances associated with these types of disorders (1).

Studies also suggest that an activated immune system has other perceivable effects on the nervous system. For example, Jonathan Kipnis of the University of Virginia and his colleagues have shown that learning triggers a stress response in the brain, which causes CD4 cells, a type of T lymphocytes, to gather at the meninges and release interleukin-4. IL-4 switches off the stress response and causes a release of brain-derived neurotrophic factor, which facilitates memory formation. Interestingly, cancer patients treated with chemotherapy drugs often experience various cognitive defects and some memory loss.  This is commonly called “chemobrain”, and these studies raise the possibility that it is a consequence of immunosuppression. Finally, an immune response against Mycobacterium vaccae has been shown to improve mood by causing neurons in the prefrontal cortex to release excess seratonin.

So it could be that the blood-brain barrier is kind of leaky after all. Understanding the connections between the immune system and the brain could lead to all sorts of ingenious treatments for various disorders. Perhaps those scientists at Stanford will utilize antibodies to develop a treatment for central nervous system repair. Perhaps we’ll one day be faced with immuno-emotive treatments for depression. Who knows? Anything is possible when a long-standing “truth” turns out not to be absolute – I’m optimistic since scientific advancement is often built on the refinement of prior knowledge.

Happiness is Catching – New Scientist

Endogenous Antibodies Promote Rapid Myelin Clearance and Effective Axon Regeneration after Nerve Injury – Proceedings of the National Academy of Sciences

Previous The Nerve Blog post About PNAS Article

Footnote:

(1) Antibodies raised against the Streptococcal M protein and human myocardial tissue, and Guillain-Barre syndrome in response to Campylobacter infection, are well studied examples of cross-reactivity between anti-pathogen antibodies with host tissues.

Scientists from the U.S. Department of Energy’s Lawrence Berkeley National Laboratory and the University of California Berkeley have delineated an alternative pathway for antidepressant function. Fluoxetine, the active compound in the widely-prescribed antidepressant drug Prozac, primarily acts as a selective serotonin reuptake inhibitor (SSRI). Many pharmaceutical agents, however, are known to exhibit multiple functions, and fluoxetine is now thought to act by a second mechanism. TREK1, a potassium channel expressed in reward-related basal ganglia, has been associated with symptoms of depression and implicated in mood regulation. Notably, it is inhibited by fluoxetine. Earlier studies have shown that TREK1 “knock out” mice display a depression-resistant phenotype, their behavior being similar to mice treated with fluoxetine. This newfound beneficial role of fluoxetine may open up a new vessel for antidepressant treatments.
Ehud Isacoff, a neurobiophysicist in UC Berkeley’s Department of Molecular and Cell Biology, and Guillaume Sandoz, a TREK1 specialist, looked at the molecular mechanisms underlying the TREK1 channel’s function. When its C-terminal domain is bound to the plasma membrane, the TREK1 channel remains open, but when the tail is unbound, the channel closes. Isacoff and his research team separated the C-terminal domain from the rest of the protein, and tagged it with green fluorescent protein. They then used voltage clamps to measure electrical currents, and fluorescence to observe the status of the channel, finding that the addition of fluoxetine causes the isolated C-terminal domain to dissociate from the membrane. This prevents current from flowing through the channel, and effectively inhibits TREK1 function. Although the effects of the C-terminal domain’s position still need to be observed with a completely intact protein, Isacoff and his team foresee promising results.

To read Science Daily’s review, click here. For the full article, click here!

to the cerebral cortex has been encountered, but Detlev Arendt, Raju Tomer, and colleagues may have found an evolutionary counterpart. The obvious answer is hidden in one simple creature– the worm. Wait, what? Yeah, you heard me. The marine ragworm, found at all water depths, has been shown to possess a tissue resembling that of our mysterious cerebral cortex.

Arendt and his colleagues used a technique called cellular profiling to determine a molecular footprint for each kind of cell in this particular type of ragworm. By utilizing this technique, they were able to uncover which genes were turned on and off in each cell, providing a means for cellular categorization. Surprisingly, mushroom bodies, regions of the ragworm’s brain that are thought to control olfactory senses, show a striking similarity to tissue found in our cerebral cortex. This intriguing discovery may provide remarkable insight into the evolutionary basis of what has developed into an incredibly important cerebral structure.

Read more about this review here, or see the original article in Cell.

To see how Suzana Herculano-Houzel thwarted the conventional correlation of brain size to intelligence, read more here.

As my good friend Cobb once told me, “Dreams feel real while we’re in them. It’s only when we wake up that we realize something was actually strange.”

OK, fine, Leonardo DiCaprio’s character from Inception isn’t real, but he does make a valid point. Oneirologists, those who study dreams, have traditionally viewed dreams as uncontrollable streams of sounds and images with the ability to induce a tremendous spectrum of emotion. However, the idea of lucid dreaming has caused the conventional understanding of dreams to collapse. A “lucid dream,” terminology coined by the Dutch psychiatrist Frederik van Eeden, is one in which the sleeper is aware that he or she is dreaming. This example of dissociation is wonderfully paradoxical in that it exhibits components of both waking and dreaming consciousness.

An American psychiatrist and dream researcher named Allan Hobson specializes in the quantification of mental events and their corresponding brain activities. Although he vehemently dismisses the idea of hidden meanings in dreams, he has embarked on a search along with other neurobiologists and cognitive scientists to decipher the neurological basis of consciousness. Hobson hypothesizes that subjects may learn to become lucid, self-awaken, and regulate plot control by intercalating voluntary decisions into the involuntary nature of the dream.

The validation of this idea would imply that the mind is capable of experiencing a waking and a dreaming state at the same time. Consequently, Hobson states, “…it may be possible to measure the physiological correlates of three conscious states, waking, non-lucid dreaming, and lucid dreaming in the laboratory.” If there is a psychological distinction between the three, there should also be a physiological difference.

The advent of lucid dreaming experimentation has not only benefitted Hollywood, but it has also provided possible treatment options for those hindered by frequent nightmares or post-traumatic stress disorder (PTSD). Methodologically speaking, the study of lucid dreaming presents a formidable challenge, but it is becoming an important component of the cognitive neurosciences.

Josefin Gavie and Antti Revonsuo have built on Hobson’s theories by proposing a technique termed lucid dreaming treatment (LDT). The key to this treatment is that the subject learns how to identify cues that facilitate lucidity during a dream, and the subject learns to manipulate the environment once lucidity is attained. The phenomenon of lucidity may prove to be a useful device in that it offers the sleeper a method to control components of the dream – altering and diminishing any threatening situation. Although the investigation of LDT is extremely new and incontestably controversial, it has shown promising preliminary results in its ability to lower the frequency of nightmares in the selected subjects.

The premise of the film Inception may be wildly hypothetical, but it has expertly amplified the current research on lucid dreams. However, researchers in the field should take a word of advice from the character of Eames: “You mustn’t be afraid to dream a little bigger, darling.”

The Neurobiology of Consciousness: Lucid Dreaming Wakes Up – J. Allan Hobson
The Future of Lucid Dreaming Treatment (PDF) – Josefin Gavie and Antti Revonsuo

Watch a video on biofeedback here: