Archive for September 2008
What makes a memory? Single cells in the brain, for one thing.
For the first time, scientists at UCLA and the Weizmann Institute of Science in Israel have recorded individual brain cells in the act of calling up a memory, thus revealing where in the brain a specific memory is stored and how the brain is able to recreate it.
Reporting in the current online edition of the journal Science, Dr. Itzhak Fried, senior study author and a UCLA professor of neurosurgery, and colleagues recorded the activity of hundreds of individual neurons making memories in the brains of 13 epilepsy patients being treated surgically at UCLA Medical Center.
Surgeons had placed electrodes in the patients’ brains to locate the origin of their seizures before surgical treatment — standard procedure in such cases. Fried made use of the same electrodes to record neuron activity as memories were being formed.
The patients watched several video clips of short duration, including such things as landmarks and people, along with other clips of Jerry Seinfeld, Tom Cruise, “Simpsons” character Homer Simpson and others. As the patients watched, the researchers recorded the activity of many neurons in the hippocampus and a nearby region known the entorhinal cortex that responded strongly to individual clips.
A few minutes later, after performing an intervening task, the patients were asked to recall whatever clips came to mind.
“They were not prompted to recall any specific clips,” Fried said, “but to use ‘free recall’ — that is, whatever popped into their heads.”
The researchers found that the same neurons that had responded earlier to a specific clip fired strongly a second or two before the subject reported recalling that clip. These neurons did not fire, however, when other clips were recalled. Ultimately, it was possible for the researchers to know which clip a patient was recalling before the patient announced it.
Fried noted that the single neurons that were recorded as they fired were not acting alone but were part of a much larger memory circuit of hundreds of thousands of cells caught in the act of responding to the clips.
The study is significant, he said, because it confirms for the first time that spontaneous memories arise through the activity of the very same neurons that fired when the memory was first being made. This link between reactivation of neurons in the hippocampus and conscious recall of past experience has been suspected and theorized for sometime, but the study now provides direct evidence for such a link.
“In a way, then,” Fried said, “reliving past experience in our memory is the resurrection of neuronal activity from the past”
Science, 2008; DOI: 10.1126/science.1164685
Internally Generated Reactivation of Single Neurons in Human Hippocampus During Free Recall.
Hagar Gelbard-Sagiv, Roy Mukamel, Michal Harel, Rafael Malach, and Itzhak Fried
The emergence of memory, a trace of things past, into human consciousness is one of the greatest mysteries of the human mind. Whereas the neuronal basis of recognition memory can be probed experimentally in human and nonhuman primates, the study of free recall requires that the mind declare the occurrence of a recalled memory (an event intrinsic to the organism and invisible to an observer). Here, we report the activity of single neurons in the human hippocampus and surrounding areas when subjects first view television episodes consisting of audiovisual sequences and again later when they freely recall these episodes. A subset of these neurons exhibited selective firing, which often persisted throughout and following specific episodes for as long as 12 seconds. Verbal reports of memories of these specific episodes at the time of free recall were preceded by selective reactivation of the same hippocampal and entorhinal cortex neurons. We suggest that this reactivation is an internally generated neuronal correlate of the subjective experience of spontaneous emergence of human recollection.
Scientists from the Gladstone Institute of Virology and Immunology (GIVI) and the National Institutes of Allergy and Infectious Diseases (NIAID) have identified a gene that may influence the production of antibodies that neutralize HIV. This new information will likely spur a new approach for making an HIV vaccine that elicits neutralizing antibodies.
Neutralizing antibodies, once produced in the host, can attack and checkmate an infecting virus.
Scientists have been striving in vain to stimulate strong protective antibodies with an HIV vaccine for years because these antibodies hold great promise for controlling HIV infection in humans. HIV is a type of virus called a “retrovirus,” which copies its RNA genetic material into DNA and incorporates it into the DNA of its host.
In 1978, researchers at the National Institutes of Health (NIH) studying a similar retrovirus in mice discovered a gene called Rfv3 that influenced the production of neutralizing antibodies that allowed the animals to recover. By 1999, they had narrowed the location of Rfv3 to a relatively small region on mouse chromosome 15, but that region contained more than 60 genes. The laboratory of GIVI Director Warner C. Greene and a team of scientists from NIAID now demonstrate that Rfv3 is Apobec3, an innate immunity gene with antiretroviral activity.
“This newfound link between Apobec3 and the production of neutralizing antibodies came as a complete surprise,” said Dr. Greene, senior author on the paper.
While the studies involved a different retrovirus infecting mice, the findings may extend to HIV. HIV uses one of its genes, Vif, to specifically disable human Apobec3 proteins and HIV-infected patients rarely make broadly neutralizing antibodies against this virus. This new study raises the possibility that drugs or vaccines that interfere with Vif might allow humans to naturally make better neutralizing antibody responses against HIV.
“We now have a host factor needed for the production of neutralizing antibodies that HIV targets and destroys,” said Gladstone scientist Mario Santiago, PhD. “This offers a fresh perspective on how to strengthen this arm of the immune response against HIV, with direct implications for immunotherapy and vaccine development.”
The scientists conducted a series of genetic experiments by mating mice with different Rfv3 and Apobec3 profiles. The researchers demonstrated that Apobec3, like Rfv3, contributes to the early control of retroviral infection in mice, and also influences specific retroviral antibody responses. In addition, they discovered that Rfv3 susceptible mouse strains that fail to make antibody responses have a natural defect in Apobec3. These results provide convincing evidence that Rfv3 and Apobec3 are the same gene.
“We set out to solve a 30-year old mystery in retrovirus biology and in the process made a discovery that might impact future development of HIV vaccines. Science really is full of unexpected twists and turns,” said Dr. Greene.
The link between Apobec3 and neutralizing antibody responses becomes even more tantalizing in view of other recent studies of people who somehow resist HIV infection despite years of frequent exposure to the virus. These individuals produce a particular type of antibody recognizing the virus and genetic mapping studies of their resistance points to a chromosomal region where the human Apobec3 genes are clustered.
The research group is now poised to investigate Apobec3 differences in these individuals and is currently screening for compounds that would rescue Apobec3 function during HIV infection.
Science. 2008 Sep 5;321(5894):1343-6.
Apobec3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infection.
Santiago ML, Montano M, Benitez R, Messer RJ, Yonemoto W, Chesebro B, Hasenkrug KJ, Greene WC.
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA.
Recovery from Friend virus 3 (Rfv3) is a single autosomal gene encoding a resistance trait that influences retroviral neutralizing antibody responses and viremia. Despite extensive research for 30 years, the molecular identity of Rfv3 has remained elusive. Here, we demonstrate that Rfv3 is encoded by Apobec3. Apobec3 maps to the same chromosome region as Rfv3 and has broad inhibitory activity against retroviruses, including HIV. Not only did genetic inactivation of Apobec3 convert Rfv3-resistant mice to a susceptible phenotype, but Apobec3 was also found to be naturally disabled by aberrant messenger RNA splicing in Rfv3-susceptible strains. The link between Apobec3 and neutralizing antibody responses highlights an Apobec3-dependent mechanism of host protection that might extend to HIV and other human retroviral infections.
A new study conducted at a large university finds more than 25 percent of those surveyed reported symptoms of tanning dependence, including symptoms similar to alcohol and drug-addicted individuals.
Suggestively, the study also found those with a tanning dependence tend to be more likely to be thin and smoke cigarettes than others. The study by researchers at Fox Chase Cancer Center is published in the September/October issue of the American Journal of Health Behavior.
Skin cancer is the most common form of cancer, according to the American Cancer Society, accounting for half of all human cancers with over a million new cases diagnosed yearly in the United States. It is reported that up to 90 percent of all skin cancers are associated with ultraviolet radiation.
For the study, Heckman and her colleagues set out to understand what proportion of college students report problems with tanning dependence and whether there are shared behaviors among those considered to be tanning dependent and those with other forms of addiction.
“Adolescents and young adults tend to put themselves at risk for later skin cancer by exposing themselves to high levels of ultraviolet radiation, so by understanding some possible reasons why, we hope to develop innovative interventions to help prevent these risky behaviors,” explains Carolyn Heckman, Ph.D., an associate member at Fox Chase Cancer Center.
Heckman and her colleagues recruited 400 students and other volunteers at Virginia Commonwealth University in Richmond, Virginia during the spring semester of 2006. Participants took part in an online survey utilizing items adapted from questionnaires used to measure traditional substance abuse and dependence. The measures assess tolerance to tanning (the need to tan increasingly frequently), withdrawal from tanning (discomfort when not having tanned recently), and difficulty controlling the behavior despite awareness of its negative impact such as freckles, wrinkles, pre-cancerous lesions, etc.
The survey included questions such as “Do you think you need to spend more and more time in the sun to maintain your perfect tan?”, “Do you continue tanning so your tan will not fade?” and “Does this [your belief that tanning can cause skin cancer] keep you from spending time in the sun or going to tanning beds?” Participants were queried about their level of intentional and incidental sun exposure, tanning booth use, and chemical sunless tanner use. The survey also asked about health-related behaviors such as body mass index, smoking, and exercise.
“The media and lay public may know tanning dependence as ‘tanorexia,’ alluding to similarities to both substance addictions and body image disorders like anorexia,” Heckman says. “There is some evidence that UV tanning dependence may have biological underpinnings like other addictions such as the production of endorphins as in the ‘runner’s high.'”
Heckman adds: “We were surprised to find that 27 percent of those we surveyed were classified as tanning dependent. The finding that almost 40 percent of those surveyed had used tanning booths and that the mean age when tanning booths were first used was 17 is also alarming.”
Interestingly, sun tanning appeared to be more closely related to tanning dependence than indoor tanning, though use of indoor tanning during warm weather also signaled tanning dependence.
Finally, the researchers say that those addicted to tanning were more likely to be thin and smoke cigarettes than others, suggesting meaningful avenues for further research into possible links among risky behaviors.
“Our ultimate goal is to find out more about the motivations for tanning so that we can develop interventions that would reduce tanning and hopefully skin cancer,” Heckman concludes.
Am J Health Behav. 2008;32(5):451-464
A Preliminary Investigation of the Predictors of Tanning Dependence
Carolyn J. Heckman, PhD; Brian L. Egleston, PhD; Diane B. Wilson, EdD, RD;
Karen S. Ingersoll, PhD
Objectives: To investigate possible predictors of tanning dependence including demographic variables, exposure and protective behaviors, and other health-related behaviors. Methods: This study consisted of an online survey of 400 students and other volunteers from a university community. Results: Twenty-seven percent of the sample was classified as tanning dependent. Tanning dependence was predicted by ethnicity and skin type, indoor and outdoor tanning and burning, and lower skin protective behaviors, as well as smoking and body mass index. Conclusions: Young adults are at risk for tanning dependence, which can be predicted by specific demographic and behavioral variables.
Key words: tanning, skin cancer prevention, addiction
There may be a very good reason why coffee and cigarettes often seem to go hand in hand.
A Kansas State University psychology professor’s research suggests that nicotine’s power may be in how it enhances other experiences. For a smoker who enjoys drinking coffee, the nicotine may make a cup of joe even better.
And that may explain why smoking is so hard to quit.
“People have very regimented things they do when they smoke,” said Matthew Palmatier, assistant professor of psychology at K-State. “If you think about where people smoke or who they smoke with, you realize that it occurs in very specific places, often with a specific group of people. Maybe it’s a reason why nicotine is so addictive — if you get used to having that extra satisfaction from things you normally enjoy, not having nicotine could reduce the enjoyment in a given activity.
“People may not be smoking to obtain a pleasurable drug state. They may be smoking in order to regulate their mood, and that effect could make nicotine more addictive than other drugs.”
Palmatier said much previous research on nicotine addiction has looked at the drug itself rather than the other factors he is studying.
“The approach we’re taking is out of left field,” he said. “But it seems to be one of the best explanations as to why people smoke.”
Palmatier has a grant from the National Institute on Drug Abuse to understand how this phenomenon can be used to better design tobacco addiction treatments, usually offered in patches and pills. He began psychological research in addiction as a graduate student and later began researching the reinforcing effects of nicotine.
“The big picture is trying to figure out why people smoke,” Palmatier said. “There are a lot of health risks, and the majority of smokers already know what they are. They want to quit but can’t. It’s not because nicotine is a potent drug; it doesn’t induce significant amounts of pleasure or euphoria. Yet, it’s just as difficult if not more difficult to quit than other drugs.”
At K-State, Palmatier studies rats that are allowed to self-administer nicotine by pushing a lever. The main source of light in their testing environment shuts off when the rats earn a dose of nicotine. After about a minute, the light comes back on to signal that more nicotine is available.
By manipulating this signal, Palmatier and his colleagues found that the rats weren’t really that interested in nicotine by itself.
“We figured out that what the rats really liked was turning the light off,” Palmatier said. “They still self-administered the nicotine, but they took more of the drug when it was associated with a reinforcing light.”
Palmatier and colleagues published a paper on their research in the August issue of Neuropsychopharmacology.
Palmatier has begun looking at how rats respond to sweet tastes after having nicotine. He said preliminary results show that nicotine has comparable effects on sweet tastes. That is, rats respond more for sugar-water solutions after getting nicotine.
“The taste aspect is really important because we can actually figure out how nicotine is increasing the subjects’ behavior,” Palmatier said. “If it makes a reward more pleasurable, then it may increase the palatability of a sweet taste.”
Palmatier said that a future phase of research would be determining whether nicotine can make unpleasant experiences more tolerable, helping explain why lighting up after a bad day at work can be tempting.
Neuropsychopharmacology. 2008 Aug;33(9):2139-47. Epub 2007 Nov 28.
Metabotropic glutamate 5 receptor (mGluR5) antagonists decrease nicotine seeking, but do not affect the reinforcement enhancing effects of nicotine.
Palmatier MI, Liu X, Donny EC, Caggiula AR, Sved AF.
Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA. firstname.lastname@example.org
Nicotine self-administration models typically evaluate the effects of smoking cessation aides on ‘primary reinforcement’ engendered by nicotine. However, the more recently described reinforcement enhancing effects of the drug are not always included in experimental analyses of potential therapeutics. We evaluated the effects of pretreatment with noncompetitive antagonists of the metabotropic glutamate 5 receptor (mGluR5) on each reinforcement-related effect of nicotine using a model in which a reinforcing visual stimulus (VS) and nicotine infusions were concurrently available. Five groups (2-lever, VS-only, NIC+VS, NIC-only, or SAL-only) were instrumented for self-administration. The 2-lever group could earn a nicotine infusion (0.06 mg/kg per infusion free base) for meeting the schedule on one lever (eg right), or VS for meeting the schedule on the other lever (eg left). The VS-only group could earn VS or saline under similar contingencies. Remaining rats could press one lever to earn both reinforcers (NIC+VS), nicotine infusions (NIC-only), or saline infusions (SAL-only); the other lever was ‘inactive’. Responding on the VS lever in the 2-lever group was greater than that of the VS-only group, reflecting the reinforcement-enhancing effect of nicotine. Pretreatment with 2-methyl-6-(phenylethynyl)-pyridine (MPEP) or 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) decreased nicotine intake as well as the enhanced responding for the concurrently available VS. In follow-up studies, replacing nicotine via experimenter-administered infusions sustained the drugs reinforcement enhancing effect; neither MPEP nor MTEP decreased the enhancing effects of nicotine. These findings are consistent with other studies suggesting that mGlu5 receptors mediate nicotine seeking, but do not alter the reinforcement enhancing effects of nicotine.
Experienced Zen meditators can clear their minds of distractions more quickly than novices, according to one of the countless brain imaging studies. Despite the care needed to interpret the data of such research settings, the results are nonetheless interesting.
After being interrupted by a word-recognition task, experienced meditators’ brains returned faster to their pre-interruption condition, researchers at Emory University School of Medicine found.
Giuseppe Pagnoni, PhD, Emory assistant professor of psychiatry and behavioral sciences, and co-workers used functional magnetic resonance imaging (fMRI) to examine changes in blood flow in the brain when people meditating were interrupted by stimuli designed to mimic the appearance of spontaneous thoughts.
The study compared 12 people from the Atlanta area with more than three years of daily practice in Zen meditation with 12 others who had never practiced meditation.
While having their brains scanned, the subjects were asked to focus on their breathing. Every once in a while, they had to distinguish a real word from a nonsense word presented at random intervals on a computer screen and, having done that, promptly “let go” of the just processed stimulus by refocusing on their breath.
The authors found that differences in brain activity between experienced meditators and novices after interruption could be seen in a set of areas often referred to as the “default mode network.” Previous studies have linked the default mode network with the occurrence of spontaneous thoughts and mind-wandering during wakeful rest.
After interruption, experienced meditators were able to bring activity in most regions of the default network back to baseline faster than non-meditators. This effect was especially prominent in the angular gyrus, a region important for processing language.
“This suggests that the regular practice of meditation may enhance the capacity to limit the influence of distracting thoughts. This skill could be important in conditions such as attention deficit and hyperactivity disorder, obsessive-compulsive disorder, anxiety disorder and major depression, characterized by excessive rumination or an abnormal production of task-unrelated thoughts,” Pagnoni says.
PLoS ONE, 2008; 3 (9): e3083 DOI: 10.1371/journal.pone.0003083
“Thinking about Not-Thinking”: Neural Correlates of Conceptual Processing during Zen Meditation.
Giuseppe Pagnoni1*, Milos Cekic2, Ying Guo3
1 Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, Untied States of America, 2 Emory University School of Medicine, Atlanta, Georgia, Untied States of America, 3 Department of Biostatistics, The Rollins School of Public Health, Emory University, Atlanta, Georgia, Untied States of America
According to some researchers, words may pack a harder punch that we realize. Psychologists Zhansheng Chen and Kipling D. Williams of Purdue University, Julie Fitness of Macquarie University, and Nicola C. Newton of the University of New South Wales found that the pain of physical events may fade with time, while the pain of social occurrences can be re-instantiated through memory retrievals.
The researchers set up four experiments to demonstrate this finding. In the first two experiments, participants reported the amount of pain they felt while trying to relive a physically or a socially painful experience. After writing detailed accounts of each experience, the participants reported how they felt.
The last two experiments were similar to the first two, except participants were asked to work on some cognitive tasks with different levels of difficulty after reliving a socially or physically painful event.
The results, published in the August issue of Psychological Science, a journal of the Association for Psychological Science, are clear. Participants who had to recall a socially painful experience reported stronger feelings of pain and relived the experience more intensely than those who had to recall a physically painful event. Furthermore, participants who only had to recall a physically painful event performed better on the difficult mental tasks in comparison to those who had to relive a socially painful event.
A possible explanation for these results could be the evolution of the human brain, specifically in an area called the cerebral cortex, which is responsible for complex thinking, perception and language processing.
“The evolution of the cerebral cortex certainly improved the ability of human beings to create and adapt; to function in and with groups, communities, and culture; and to respond to pain associated with social interactions,” the authors wrote. “However, the cerebral cortex may also have had an unintended effect of allowing humans to relive, re-experience, and suffer from social pain.”
Psychological Science Volume 19, Issue 8, Date: August 2008, Pages: 789-795
When Hurt Will Not Heal: Exploring the Capacity to Relive Social and Physical Pain
Zhansheng Chen, Kipling D. Williams, Julie Fitness, Nicola C. Newton
Recent discoveries suggest that social pain is as real and intense as physical pain, and that the social-pain system may have piggybacked on the brain structure that had evolved earlier for physical pain. The present study examined an important distinction between social and physical pain: Individuals can relive and reexperience social pain more easily and more intensely than physical pain. Studies 1 and 2 showed that people reported higher levels of pain after reliving a past socially painful event than after reliving a past physically painful event. Studies 3 and 4 found, in addition, that people performed worse on cognitively demanding tasks after they relived social rather than physical pain. Implications for research on social pain and theories about social pain are discussed.