NRSC 4132 Blog

Recent consensus numbers indicate that roughly 20 million, or about 10%, of the current U.S. population reported practicing meditation in the last year! To many of us at CU, the practice of meditation is all too familiar - Boulder, CO is one of the most yoga- and meditation- active cities in the U.S.

A recent study in the Journal of Neuroscience by Zeidan et. al (http://www.jneurosci.org/content/31/14/5540.abstract) analyzes an interesting application of meditation: modulation of pain. In particular, the Shamantha model of meditation was examined, one which involves sustaining attention on the "changing sensations of breath, monitoring discursive events as they rise, disengaging from those events without affective reaction, and redirecting attention back to breath". In this study, the discursive event was pain, and subjects were assessed for their ability to dissociate cognition of the pain stimulus from pain response.

The study employs a novel form of fMRI called pulse arterial spine labeled (PASL) MRI, a form of imaging that quantifies cerebral blood flow (CBF). Blood oxygen-level dependent (BOLD) fMRI, the conventional form of fMRI, is useful for monitoring short spurts of activity, but it is susceptible to slow drifts in signal intensity over extended periods of time. Because the practice of meditation often requires ample time, PASL MRI is better suited than BOLD fMRI.

The experiment consisted of 15 healthy volunteers. Three groups were sampled: a control group that received no training, an experimental group that only received directions to focus attention to breathing (ATB), and an experimental group that was taught Shamantha meditation. Each group was brought into a neutral environment and was presented with a 6 min. noxious heat stimulus (at 49 deg Celsius), during which the control group was instructed to rest, the ATB group to focus on breathing, and the meditation group to meditate. Two MRI readings were taken on all groups during presentation of noxious stimuli: pre- and post-meditation training. Additionally, test subjects were asked to rate unpleasantness of pain through the Freiburg Mindfulness Inventory (FMI) shortform.

Interestingly, the results show that attention to breath alone has no effect on modulating pain response; ratings of pain intensity and unpleasantness were identical between the control and ATB groups prior to meditation training. After meditation training, the experimental groups exhibited a 57% decrease in pain unpleasantness ratings and a 40% decrease in pain intensity ratings relative to the control group. Statistical analysis shows that meditation-induced reductions in pain were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive recognition of pain. This may seem paradoxical at first, as a majority of past studies have reported increased activity of these areas increases pain experience.

It is important to note that Zeidan et. al clarify the increased activity of these areas with the concurrent reduction of activity in the orbitofrontal cortex (OFC), an area of the brain associated with emotional evaluation and response. Grant et. al (http://www.ncbi.nlm.nih.gov/pubmed/21055874) report a similar de-coupling of the dorsolateral prefrontal cortex (DLPFC) and the cingulate, suggesting that the DLPFC (like the OFC) functions to generate emotional response after the cingulate receives afferents from pain stimuli. Given this novel model of pain, it is not surprising that the anterior cingulate cortex and anterior insula were active in meditating individuals; the heightened activity of these areas allowed them to be aware of discursive events (pain stimuli), but the reduced activity of the OFC allowed them to dissociate their pain response and refocus their attention to breathing.

These results show that meditation may be a powerful, natural way of dealing with pain. In an era where opiates and pain relievers are often relentlessly abused, meditation may be the perfect solution. Maybe one day, we'll see NFL athletes meditate at the end of practices and games, or physical rehabilitation patients meditate daily to overcome the pain of a healing injury. Only time, and more research, can tell.

Psychiatric disease genes in humans are exceedingly difficult to study. The disease features and symptoms present can differ among individuals and may differ in severity. Polygenic inheritance and gene-environment interactions play a role in these diseases, making it difficult to decide how many genes contribute to the disease and whether a behavior should be attributed to genes or to environmental influences. For these reasons, using mouse genetics is beneficial; the environmental and genetic makeup can be controlled for. In order to be able to generalize the results to humans, the researchers in this study created transgenic mice that expressed the human orphan nuclear receptor 2E1 (NR2E1) to see how the gene affected the behavior of the mice. Abrahams et al. studied four types of mice: wild-type, transgenic (contains human NR2E1 gene), fierce (NR2E1 deletion), and rescue (NR2E1 replaced during adulthood). Without NR2E1, mice would demonstrate pathological violence, in addition to physical abnormalities. These NR2E1 null mice are referred to as "fierce." Additionally, the presence of a transgene spanning human NR2E1 can eliminate the brain and eye abnormalities and restore normal behavior to fierce mice, implicating possible treatments for psychiatric diseases that involve pathological behaviors.

Physical abnormalities were abundant in fierce mice, whereas transgenic and rescue mice were phenotypically indistinguishable from wild-type mice. Brain abnormalities in fierce mice included hypoplasia of the olfactory bulbs and anterior cortex, which was determined by an analysis of the surface areas of these regions. This damage left midbrain colliculi exposed. Additionally, the brain contained an abnormally small forebrain, abnormally shaped cingulum, poorly defined piriform cortex, smaller anterior commissure, abnormal cortical lamination, a reduction in striatal volume, an enlargement of corticostriatal fibers, and a thin external capsule of the corpus callosum. Eye abnormalities included radial asymmetry, mottling of the retinal pigment epithelium, and a reduction in retinal vessel number. It should be noted that rescue mice had a significantly reduced vessel number compared to wild-type and transgenic, though they were phenotypically normal by qualitative and quantitative analyses. Behaviorally, fierce mice were more spontaneous, more aggressive (to the point that they would attack or kill mates), and less social than the mice of the other three genotypes.

NR2E1 is transcribed in regions important for neurogenesis and it is thought that it suppresses the differentiation of neuronal stem cells. Since NR2E1 deletion produces physical abnormalities in the brain, it is thought that the available stem cells cannot form into the proper structures through neurogenesis. Although this explains the physical abnormalities, it remains unknown whether abnormal behavior results from improper brain development or from a deficiency in NR2E1 signaling. In humans, it is more likely that a subtle variation of NR2E1, rather than a gene deletion, is at work to produce behavioral abnormalities. For instance, NR2E1 may play a role in bipolar disorder, and only a small portion of the gene is disrupted. Abrahams et al also note that genes that interact with NR2E1 may be involved in psychiatric disease, so association studies should be done to examine other contributors to psychiatric diseases.

Ultimately, few transgenic rescue experiments have been done, although they are increasing in popularity. The few that have been done have prevented embryonic lethality using a human gene as a rescue, but have not improved abnormal behavior. This study was instrumental in demonstrating that rescue genes can correct abnormal behavior.

Source: http://www.jneurosci.org/content/25/27/6263.full.pdf+html?sid=44333731-d47a-48fc-80df-d59af7a07702

Forget everything you thought you knew about the differences between men and women. The latest research has shown that the differences between the sexes run much deeper than body structures and the equipment they have downstairs, to the point that even the way they think might be distinctly masculine or feminine and attempting to understand the thinking of the other sex may be a larger gap to cross than previously thought. Now there's much promise that recent scientific developments may help create understanding of atypical sexual activities, preferences, and anatomies. Margaret M. McCarthy and Arthur P. Arnold of the University of Maryland and UCLA, respectively, have culled the research of recent years to update the last century's model of sexual development in their May 2011 Nature Neuroscience published review, Reframing Sexual Differentiation of the Brain.
Things used to be simpler in the past when an animal simply had either testosterone or estrogen produced in the gonads and then those molecules would go off into tissues and structures all over the body and exert influences over long periods of time. Now, McCarthy and Arnold tell us that that's only part of the story. Recent research has shown that estradiol, the major masculinizing and defeminizing metabolite of testosterone, can be synthesized on demand in neurons and have rapid effects, that genetically castrated rats still behave like males, and that synaptic connection strategies differ between the sexes. The authors are presenting an entirely new, more nuanced model of sexual differentiation that takes into account the multiple parallel signaling mechanisms recently discovered and the role of environment.
Their model is helping to explain why men are from Mars and women are from Venus. It turns out that there are many differences in brain structure between the sexes. Males tend to have larger spinal cord nuclei and medial preoptic areas of the hypothalamus than women, which is to be expected since these areas control penis muscles and masculine sexual behavior, respectively. What's more surprising is that females grow more new cells in the amygdala soon after birth, and males get more in the hippocampus, areas more typically related to fear and memory than sexual behaviors. Would that be something that would affect the way their brains function, making them think differently? Well, if not that then certainly the recent discovery that male dendrites are longer and more branched than females in the ventromedial nucleus of the hypothalamus, along with differences in spine density as much as 2-3 times between the sexes in diverse areas may clear some things up. With such varied connection strategies, it's no wonder that the sexes often can't follow each other's thoughts; the ideas may end up in completely different parts of the brain depending on whether the listener has a male or female brain. Indeed, proportionally larger brain areas may contribute a larger slice of the overall cognitive set, and so it may make sense that women and men will have different strategies for solving problems.
Another extension of the authors' work worthy of note is that their model makes room for not just dimorphism of sexual behavior and physiology, but polymorphism. Cloning has made possible the creation of XX genome rats with testes and XY genome rats with ovaries by moving the testes-determining gene, Sry, off of the Y chromosome to an autosome. Many other things stayed the same though, regardless of gonadal sex, such as habit formation patterns, alcohol preference, and aggression. This means that the things that make a person male or female are likely largely independent of what sex organs they have. Certainly there's room in the human genome, particularly atypical genomes, for combinations of genetically influenced traits all across the spectrum. Hopefully this enlightenment can lead to more understanding and tolerance in a world know for its brutally against those with sexual differences.
These more nuanced new ways of thinking have a certain charm in their complexity. I remember being taught as a child that all things male came from testosterone, all things female from estrogen, and then being appalled to hear in my teens that women had testosterone too and that it was a good thing. It's pleasant to imagine now describing to my children this more complex understanding and watching their minds engage and take in the realization of the depth of the mystery of the world.

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