NRSC 4132 Blog

We have all heard the theories of seeing a bright light or your life flashing before your eyes right before you die. In fact, accounts of these near-death experiences can be traced back to literature of ancient Greece. Most theological doctrines share the idea that death is a passing to an afterlife, an eternal utopia where we are reunited with loved ones. Interestingly, 3% of Americans declare to have had a near-death experience [1], and their accounts have recently been discussed in several books. These books, however, tend to leave out physiological explanations for these experiences and rely solely on paranormal explanations.

The Medical Research Council of Cambridge and University of Edinburgh took it upon themselves to research the neurological events behind these notions. They found that contrary to popular belief, there is actually nothing paranormal about these experiences. Instead, near-death experiences are the manifestation of normal brain function gone awry during a traumatic, and sometimes harmless, event [2].

In order of occurrence, the basic features of near-death experiences include awareness of being dead (50%), meeting with deceased people (32%), moving through a tunnel (31%), and having an out-of-body experience (24%) [3]. Only 56% of those who had a near-death experience associated it with positive emotions, which is contrary to the belief that feelings of euphoria and bliss are associated with these experiences.

The following are scientifically-based explanations on these peculiar experiences. Cotard syndrome is a documented disorder characterized by the feeling that one is dead. It has been associated with the parietal cortex and the prefrontal cortex, and just like the near-death experience equivalent, it is likely an attempt for the brain to make sense of a strange experience the patient is having. Out-of-body experiences are common during REM sleep, and results from a failure to integrate multisensory information from one's body, which results in the disruption of self-representation. A tunnel of light can be explained by visual activity during retinal ischemia, which is when the blood and oxygen supply to the eye is depleted. It has been to feelings of extreme fear because the same sensation has been reported by pilots flying at G-force. As far as meeting deceased people, several neuroscience studies have proved that brain pathology can lead to visions of souls of the dead, angels or a religious figure that are prevalent in fiction and personal accounts. Examples are hallucinations of Alzheimer's or Parkinson's disease, and patients with abnormal dopamine function. Theoretically, many hallucinations are due to brain structures over-compensating near damaged areas or making sense of noise from damaged areas.

Additionally, the fact that the drug ketamine often mimics these experiences including hallucinations, out-of-body experiences, and positive emotions such as euphoria, dissociation, and spiritual experiences further supports the position these accounts are due to neurophysiological parameters, not paranormal phenomenon.

Obviously, further evidence is required if the ideas such as these will ever be fully demystified by the reliable realm of science. Though it may come as a disappointment to some (and others may even refuse to accept it), it is important that these neurobiological-based findings are spread.

[1] Schmied, I. et al. (1999) Todesna¨heerfahrungen in Ost- und Westdeutschland eine empirische Untersuchung. In Todesna¨he: interdisziplina¨re Zuga¨nge zu einem auergewo¨hnlichen Pha¨nomen (Knoblaub, H. and Soeffner, H.G., eds), pp. 217250, Universita¨tsverlag Konstanz

[2] Article Source: http://download.cell.com/trends/cognitivesciences/pdf/PIIS1364661311001550.pdf?intermediate=true

[3] van Lommel, P. et al. (2001) Near-Death experiences in surviviors of cardiac arrest: a prospective study in the Netherlands. Lancet 358, 20392045

In case you don't know what they are, throat lozenges are those chalky, powdery tablets primarily composed of zinc that you take to alleviate sore throat pain. Similar to a cough drop, they've been around for years and seem to be part of many people's remedy regimen to treat such symptoms of the common cold. Pain is one of those feelings that not many of us like to deal with or even think about. Whether you are taking aspirin, acetaminophen, or throat lozenges to manage throat pain, it is known that many options are abound in the marketplace.

Pain is an unpleasant sensory and emotional reaction that usually motivates us to seek some sort of "pain-killer." Sometimes it even gets to the point where we don't care to know or what extent we have to go to alleviate our pain--symptoms of such "pain-killers" disregarded. An extensive amount of funding and research has gone into the clinical aspects of pain management drugs including not only over-the-counter pain medications such as Tylenol and Advil, but chronic pain anesthetics with detrimental side effects. Such drug categories include neurolytic blocks, narcotics, opiates, and other analgesics. Side effects from all of these drugs, acute and severe, range from topical rashes and swelling to addiction and cardiac arrest. Holistic healing, be it through ?mind over matter? or ingesting natural antidotes, may be a way to avoid pain killers that bring severe side effects with them. According to comprehensive research involving zinc in last month's issue of Nature Neuroscience, perhaps there are some natural treatment methods of pain management.

Zinc, as previously mentioned, is a metallic chemical element that is readily available and affordable throughout the marketplace. In fact, it is so copious, that it is the 24th most abundant element in the Earth's crust, and the second most prevalent trace element in the body according to Nozaki's et al. investigation. Not only is it essential for life and crucial for cellular metabolism, but Nozaki et al. have discovered a role for zinc in brain functions such as neurological disorders and pathological pain management. The trouble with studying this element is the myriad of potential zinc targets on the molecular basis. Nozaki et al. noted that NMDA receptors are one of the potential synaptic targets for zinc effects of excitatory transmission and have key roles in both the physiology and pathology of the nervous system. Notably, these receptors contribute to pain transmission and the development of chronic pain.

As we understand, there are various subunits that comprise the NMDA receptor (NR1 and NR2 subunits). In particular, the NR2A subunit, which is widely expressed in the adult nervous system, has an intense sensitivity for extracellular zinc, or zinc taken in the body beyond endogenous levels of zinc. Using knock-in NR2A-H128S mice, they found that high affinity zinc binding to the NR2A subunit is enough to dampen NMDA receptor function in pain pathways throughout the central nervous system. Though Nozaki et al. have not found the precise location of the site where zinc diffuses in the vicinity of NMDA receptors, they did find that NMDA-dependent spinal long-term potentiation, a well-known substrate for hyperalgesia, is blocked by exogenous zinc.

This is an enormous discovery in terms of future experimentation and the potential role of the natural element zinc in place of dangerous pain-management pharmaceuticals. It's absolutely incredible to me how technology is unveiling Mother Nature's organic remedy for so many of the problems and illnesses in today's society. Not that I doubt the use of western medication and synthetic pharmaceuticals as treatment options for various illnesses, but I strongly condone taking natural elements found on this planet with a far shorter list of side effects. A lesson to consider: keep on sucking on those zinc throat lozenges when you have a sore throat!

Raw sugar. Where did it go? I don't remember the last time I actually saw one-hundred percent, real, authentic sugar on the table the last time I was seated at a restaurant. Whether it's an iced tea, coffee or whatever I'm ordering that doesn't arrive at the table sweet enough to my liking, the only quick option I have is to choose one, or many, of those artificial sweetener packets located within arms reach. One might view one of those many companies who put so much time and money into making these packets so readily available at nearly every restaurant, a small additive solution to America's obesity issue that I discussed last week. Do you want sweet and low? Equal? How about Splenda? Or maybe even Truvia. Regardless, they're all fake. And for the most part, they all satisfy our need to make not only beverages, but confections and whatever else, taste more sweet.

The molecular mechanisms involved with sweet taste and the impact of artificial sweeteners are still not completely mapped out. Before I get into some of the interesting findings in the July 11' edition of The Journal of Neuroscience, let me give you a piece of advice: next time you reach for that white ceramic square containing all those fun colors of artificial sweeteners, stop yourself before you do and ask for some real sugar--it's in your best interest.

Taste qualities can be broken down into five major categories; sweet, bitter, sour, salty, and umami. Thus far, it has clearly been identified that the family C G-protein coupled receptor Tas1R2 and Tas1R3 heterodimer mediates the primary sensory transmission process of sweet taste perception. This receptor can be stimulated by many of these diverse natural or synthetic sweet ligands and proteins.

In Bo Liu et al.'s research involving artificial sweeteners, he and his team heterogeneously expressed and functionally assessed these receptors from a squirrel monkey which belongs to the genus Samimiri of New World monkeys. Using receptor chimeras between humans and squirrel monkeys, species-dependent sweet taste differences were determined by a combination of a few specific interaction sites on the Tas1R2 and Tas1R3 receptors. Using two primary ingredients to some (aspartame and neotame), but not all, artificial sweeteners, they found that Old World monkeys but not New World monkeys are able to taste the sweet sensation of such products. In their analysis of such results it was noted that specific residues, are required to taste something sweet and that the extracellular domain of the human Tas1R2 receptor is a critical site and contains important molecular determinants for activation by aspartame and neotame. Old World monkeys (and rats) had a hydrophobic binding site on these receptors which no longer exists on the New World species.

Though Liu et al. did not go on to mention any further experimentation or draw parallels for the human population, considering their BLAST search between the primates and human samples used was a strong 89% correlation some inferences can be made. To what extent evolution of New World monkeys and rats plays a part in this de-sensitization remains unknown, however, what happened to those specific species that hasn't happened to Homo sapiens yet? Regardless of whether or not we're going to potentially lose the ability to percept aspartame and neotame in the future, artificial sweeteners are already known to be bad for human homeostasis. Even though products such as Splenda (Sucralose) and Truvia claim to be all natural and aren't involved in this research, in large quantities, artificial sweeteners can be carcinogenic and in some studies have shown to actually cause weight gain. Considering the vast research boycotting the use of such products, I think it's best to say that we should just stick to the old fashioned way of making our drinks sweeter--with pure sugar cane. Whether you like it raw or not, your sugar cane that is, it just seems to be the smarter option.

Presently, we live in a society that has become increasingly dependent of pharmaceuticals as the great panacea for our discomforts and diseases. Treatment of neurological disorders is most commonly mediated through trial and error dosing of medication. This trend has steadily increased since the 1950s with the use of antidepressants and accompanied the closing of most of America?s mental hospitals. The emphasis on personal treatment and therapy has lost ground to the administration of singular chemicals (or combinations) that alter pathways with predicted but not completely understood chemical results (due to the highly interconnected nature of these chemical pathways.) This method can work wonders, many patients with severely debilitating neurological disorders such as schizophrenia often find great relief in their treatments and are able to live without or with minimal assistance. Drugs are also often a cheaper solution to the problem (compared to high levels of therapy or institutionalization.)
Unfortunately though this practice of pharmaceutical treatment has many limits; Many antidepressants that have been prescribed over the years have been found later to increase suicidal tendencies. Some people have genetic or environmentally caused dispositions that increase or decrease the drug potency or its negative side effects. Some drugs are sought out not for curing disorders or diseases but for recreational or ability enhancing uses (like the highly prevalent the misuse of adderall among students.) Then, of course, there are disorders or injuries which impair the nervous system for which there is no known treatment or specific biochemical pathway on which to act upon. For these reasons many scientists and clinicians are using nonpharmacological treatments, especially the utilization of sensory input, to help ease and heal their patients.
A great leader in this movement towards alternative forms treatment is Dr. V. S. Ramachandran. Dr. Ramachandran is a neuroscientist at the University of California San Diego and has helped people suffering with a strange neurological disorder known as phantom limb syndrome without surgery or drugs. Phantom limb syndrome is the experience of feeling of the presence of an amputated limb, it can be quite painful and is believed to be caused by lack of feedback inhibition (the brain tells the missing hand to clench but the hand cannot clench so the brain tells the hand to clench harder etc.) By using a ?mirror box? Ramachadran has found that he can use external sensory input (the patient ?seeing? his missing hand clench by using the reflection of his present hand) to override the jammed signal.
Another example of novel drug-free therapies has been the use of electrodes to serve as external sensory devices in both the treatment of vestibular malfunction and to return sight to the blind. A grid of electrodes is used in both cases and can be used as a sort of balancing meter for vestibular treatment or as a sort of low resolution black and white television (with an on electrode being white and an off electrode being black.) These treatments have shown success for many patients and may become more popular as technology advances.
These exciting and alternative therapies are of course limited, but may open the door to other forms of treatment for difficult to medicate neurological disorders.

Have you ever experienced a ?gut feeling?? Gut feelings are also known as intuitions. I?m sure you?ve all hear about your mother?s intuition? if not ? I?m sure she?ll tell you ?Mother knows best!? We all know things that weren?t taught to us?but we still know them. For example, best friend says she?s ?okay? but you know she isn?t or your newborn is sick. A gut feeling is a sudden, unexplained judgment where we don?t know the source of origin.

Science has started to research how the stomach and brain are interconnected. ?The concept that the gut and the brain are closely connected, and that this interaction plays an important part not only in gastrointestinal function but also in certain feeling states and in intuitive decision making, is deeply rooted in our language.?(Mayer, 2011)

In the August issue of Nature Review Neuroscience, the article ?Gut feelings: the emerging biology of gut?brain communication,? talks about the foundation of why there are such feelings and the pathways that are taken to create those feelings. ?Recent neurobiological insights into this gut?brain crosstalk have revealed a complex, bidirectional communication system that not only ensures the proper maintenance of gastrointestinal homeostasis and digestion but is likely to have multiple effects on affect, motivation and higher cognitive functions, including intuitive decision making.?(Mayer, 2011) The article discusses the enteric nervous system and the signaling pathways that the gut and brain used to communicate ??The brain communicates to the viscera, including the gastrointestinal tract, through multiple parallel pathways, including the two branches of the autonomic nervous system (ANS), the hypothalamic?pituitary?adrenal (HPA) axis and the sympatho?adrenal axis (modulating the gut-associated lymphoid tissue), and descending monoaminergic pathways (modulating gain of spinal reflexes and dorsal horn excitability). ? (Mayer, 2011) The article then discuss the effect of the stomach to the brain. Most of the consciously perceived information about the stomach is that it?s used for digestion?this isn?t new information. ?However, recent evidence suggests that various forms of subliminal interoceptive inputs from the gut, including those generated by intestinal microbes, may influence memory formation, emotional arousal and affective behaviours.? (Mayer, 2011)

So why do we make decision based off no information but off our ?gut feelings?? Mayer suggests that we have some ?neurological basis? when it comes to our gut-interactions. She suggests that our gut feeling based decision is due to an interoceptive map of gut responses that develops in infancy and continues to develop throughout our stages of life.

The future holds new research on the crosstalk between the stomach and the brain. The primary focus is the mapping associated with the two. ?This includes the remarkable success in mapping the functional neuroanatomy of the ENS, in our understanding of how the brain modulates these ENS circuits and gut functions, and in unraveling the complexity of gut to brain signaling through multiple parallel but interacting communication channels.? (Mayer, 2011) With our current advances in the study of gut feelings we still have many unanswered questions? stay tuned for what science discover next.
To read full article, please visit https://cuvpn.colorado.edu/nrn/journal/v12/n8/full/,DanaInfo=www.nature.com+nrn3071.html

We Americans are so accustomed to a lifestyle of instant gratification, ease, and leisure; especially when making daily choices of what we consume individually. It's no surprise we face an unprecedented epidemic of obesity in this nation when you look at how corporate food companies cater to our demand for easy availability of virtually any type of food one could ever crave. Obviously location takes an important roll as well, but for most of us residing in urban areas, our communities are saturated with endless food options. We no longer need to get out of our car to get an eight-hundred calorie caramel macchiato in the mornings. There's something to be said about the fact that one can obtain endless high-fat and high-caloric meals at the very thought of hunger.

Researchers and statisticians seem to be very compelled in not only updating the nation's obesity statistics, but also in finding new ways to potentially counteract America's modern obesity outbreak. In the past, some of us have resorted to other behaviors and procedures in compensation such as workout rituals, personal trainers, diet pills, and even extreme actions like stomach-stapling, liposuction, etc. Regardless of whether they worked or not, it's about time something new came around.

In last month's publication of Nature & Neuroscience, and interesting study using mouse mutants to research insulin receptor function in the ventromedial nucleus of the hypothalamus (VMH). Provided that high-fat diets lead to the production of severely high levels of insulin (which we all know can initiate cascades of detrimental health issues such as diabetes, high blood pressure, etc.), Klöckener et al. suggest brain mechanisms in the VHM which if genetically modified, may be applicable to humans and anti-obesity treatments.

The VMH is a rather unclear and grey portion of the brain in terms of the knowledge that we currently know about it. We do know however, that it serves as one of the primary locations in the hypothalamus that mediates nutrient sensing, metabolism, and insulin receptor signaling. To guarantee an optimal energy environment for reproduction, the body monitors energy availability indirectly with the help of insulin and leptin that consistently circulate in the body. These two hormones can act to store fat as well as alert other metabolizing processes.

Steroidogenic factor 1 (SF-1) positive cells distribute across large parts of the VMH are directly involved with controlling systematic metabolism. These cells are highly responsive to insulin. Klöckener et al. identified a subpopulation of insulin-SF-1-positive cells in the VMH distinct from leptin-responsive neurons. They found that the systematic deletion of the insulin receptor in SF-1 expressing cells of the VMH caused no immediate changes in homeostasis. However, when both the control and mutant mice were exposed to high-fat diets, the modified SF-1 cell mice were protected from the development of obesity. It was reasoned that this protection from obesity was due to higher leptin sensitivity, since insulin was rendered useless in the mutant mice. Following this discovery, they found that the reinstatement of PtdInsP3 signaling downstream of the insulin receptor made the mutant mice that were previously protected from obesity, vulnerable again.

Even though all of the processes VMH carries out sill remains unclear, the mechanisms involved with insulin and high-fat diets are becoming clearer. These findings are on their way to future investigations where potential anti-obesity therapeutics may be revealed.

I think it's awesome that researchers are unveiling new methods that can potentially solve this epidemic in the near future and I strongly support such research for the benefit of the population. This compelling issue has not been mitigated to a satisfactory level even with counteracting behaviors as mentioned above. Statistically, just below twenty percent of the population in Colorado is diagnosed as clinically obese. It's ironic thought because Colorado tops the list for the least obese state in the nation. We clearly have to keep working, researching, and making changes in order for a valid solution to be found.

In Mike Nichols film "The Birdcage," Albert played by Nathan Lane, is an insecure, emotional-rollercoaster drag queen whose partner Armand, played by Robin Williams, is an unwavering, cautious entrepreneur. Albert's insecurities get the best of him on stage in addition to his relationship woes that cause him to act in a neurotically unstable fashion. When his self-image gets the best of him, he relies on "Pirin" tablets supplied by his houseboy to calm his nerves and give him so called confidence so he can perform on the stage, and keep the guests coming. Completely clueless to the fact that the "Pirin" tablets are just aspirin tablets with the "A" and "S" scratched off, Albert's "need" for them remains a religious habit.

Albert's surrender to the placebo effect isn't necessarily out of the norm when taking the general population into perspective. Research published in the Journal of Neuroscience surrounding the neurobiological mechanisms of the placebo effect could be used as an excuse as to why people like Albert succumb to pseudo-western medicine prescriptions and expectations to better their condition.

The placebo effect is a psychobiological phenomenon that can be attributable to different mechanisms, including expectation of clinical improvement. In Fabrizio Benedetti's research encompassing this effect, he notes that no matter what medical treatment a patient is receiving, their therapeutic outcome is surrounded by psychosocial contexts. The placebo effect has become a modern topic of interest among scientists and the general public in light of the fact that "we must broaden our conception of the limits of endogenous human capability."

If we can rely on our own homeostatic processes and reduce our usage of unnecessary western medications, some of which have detrimental side effects later in life, we can potentially better our overall well being. In Parkinson's disease research, a pool of patients was given an inert substance (the placebo) and were told that it was an "antiparkinsonian drug that produces an improvement in their motor performance." Results displayed that with their capability to measure endogenous dopamine release, the placebo-induced expectation of motor improvement activates endogenous dopamine in those patients. This ultimately led the patients to better therapeutic outcomes.

We know that the placebo effect is real. Patients involved in thousands of placebo-induced studies have shown a better therapeutic outcome when their expectations and knowledge of recovery is good. Recent uproars are now suggesting the idea of anti-depressant medications being glorified placebos. On account of the pharmaceutical boom for mental illnesses, scientists are heavily researching not only the accuracy of such drugs but the validity.

What does this mean for the Albert's of the world and the rest of us taking conceptually risky medications? Well, even though the thought of people halting their prescription use and relying on their endogenous human capability to run the ship seems amiable, it's not practical. People need medications. However, I definitely think pharmaceutical companies are where the problem lies. How do we know that the neurological drugs that our doctors are telling us we need are in fact necessary or even beneficial for that matter? We don?t. But there's no reason why we shouldn't question the men and women who attended a higher level of education to write us these prescriptions.