Traumatic Memories, Part 1

Most of the time, most of us wish we could remember things better. But some of the time all of us have things we wish we could forget. Traumas, emotional upset, grief — all can be more than we can wish to bear.
     When anxiety becomes too intense and persistent, the level of stress becomes de-bilitating. There are many negative effects on the adrenal gland and its production of hormones that are designed to cope with stress. Beyond that, the brain is also affected. These effects are the hallmark of what is commonly called “Post-traumatic Stress Syndrome” (PTSD), which seems to be a common and growing problem with American soldiers returning from Iraq and Afghanistan. While older people are in the wrong age bracket to have this problem, they are very likely to know about PTSD in soldiers and may even have children or grandchildren who have PTSD.
     You don't have to be a combat soldier to develop anxiety disorders such as PTSD. Everyone has probably had some kind of traumatic experience that caused a serious emotional trauma. Such experiences are always associated with a host of cues, many subconscious, that are part of the original learned traumatic experience. The learned association may be remembered at some unconscious level long after the conscious memory is lost.
      Sensory cues, even if not recognized consciously, can trigger recall of disturbing memories or even just the negative emotions that went with the original bad event. Sometimes this is the basis for so-called “anxiety attacks,” which seem to come out of nowhere.
      Anxiety disorders are among the most common mental health problems and are often treated with so-called extinction therapies. That is, therapy is geared toward unlearning (extinguishing) our fears by deliberately re-living the disturbing event under safe conditions and thereby learning we can cope.      
Modern psychotherapy for phobias, anxiety, and PTSD often involves recalling the original bad event under reassuring conditions. But this has to be done with conscious re-assessment and realization that the original negative emotions and fear are no longer applicable because the re-living is a simulation in a safe environment. One creates a new learning substitute for the original emotional trauma.
      The re-living must include dealing with the negative emotions in the light of reason and new emotional experience. Therapy requires critical thinking about thoughts and feelings, especially those that are unhelpful and unrealistic. The patient is gently led to face memories anew and to learn new ways of thinking and behaving. This re-creation of the bad event allows us to extinguish memory of the original bad situation and its negative emotions.
      I recently got an up-date in this area of research at a seminar by Gregory Quick from the Department of Psychiatry at the University of Puerto Rico. As Pavlov showed, memory extinction is a basic phenomenon even in simple animals. If you repeatedly ring a bell and then stress a rat, it soon learns to become distressed the next time it hears that bell, even after you stop the stress. In the lab, this is manifested by the rat showing freeze behavior. But, if you repeat the bell enough times without the stress, the conditioned response (CR) (freeze behavior) eventually becomes extinguished.
     At first, scientists thought that extinction erases the memory of the CR. But extinction really creates a new memory that competes with memory of the original CR. Both memories co-exist. Over time the extinction memory may be lost, and the CR can return. The implication is that, just as ordinary learning needs rehearsal, so does extinction learning.
     Therapy for emotional trauma and PTSD might be more effective if therapy were approached like a conventional learning experience whose memory is affected in all the usual ways. Recall what was said about extinction being a case of new learning. Re-learning of an extinguished response occurs much more readily than it does for an initial extinction learning. This is an example of priming. It’s like re-learning a foreign language. It goes easier the second time and the memory might be even more dependable.
      Since memory of an emotional CR learning experience and its extinction can co-exist, these two memories compete for which one is strong enough to survive long-term. Sadly, the CR memory is often stronger. Cues are extremely important to both forming and retrieving all kinds of memory. It seems likely there are many more explicit cues for CR memories than for extinction memories. Therapy should be aimed at enriching the number and variety of cues associated with extinction learning. Rehearsal is likewise important. So far, nobody seems to have given that much thought.
     There is another aspect to emotional learning: learning to learn. If you have multiple anxieties, they may generalize and "spread" to facilitate learning new anxieties. The corollary would be that learning how to promote extinction could also generalize and thus increasing the general ability to cope with emotional trauma. Obviously, for one's brain to learn how to do that, one would need to begin with a single relatively easy extinction learning task.
    
     Dr. Bill Klemm is a Professor of Neuroscience at Texas A&M University. Visit his book site and blog at ThankYouBrain.com for more help on improving learning and memory. Copyright 2010, W. R. Klemm

Music Training Helps Learning & Memory

Music training is good for the brain. Nina Kraus, a prominent brain researcher at Northwestern University, says that "music training leads to changes throughout the auditory system that prime musicians for listening challenges beyond music processing." The research in her laboratory and that from other labs suggests music training does for brain what exercise does for body fitness. She says "music is a resource that tones the brain for auditory fitness."

Musicians are commonly studied models for neural plasticity, which refers to the ability of learning experiences to change the brain chemically and physically. Musicians have more brain grey matter volume in areas that are important for playing an instrument and in the auditory cortex, which processes all kinds of sound. Of course, the effects of music training are most robust for processing of music. But benefit transfers to speech, language, emotion, and general auditory processing.

In general, auditory learning requires formation of efficient sound-to-meaning relation-ships, which in turn require attending to sensory details (fine-grained properties of sound such as pitch, timing and timbre), but also thinking skills related to integrating sensory input and operating on it in working memory.

Music training confers ability to assess the relevance and predictability of information-bearing elements in an auditory signal. So, even in non-musical contexts, such as listen-ing to a speech, lecture, or sound track in a movie for example, musicians should learn and remember more of the content than non-musicians. Musicians also have an advan-tage when it comes to learning the sounds of a new language.

Music training imposes a high working-memory load. That can be a good thing, in that it helps you expand your working memory capacity, and thus reduces the impairing effects on memory of working memory overload. Increasing working memory capacity also improves the ability to think, as manifest in IQ scores. Since musicians usually have greater working memory capacity, it doesn’t mean they are smarter than anybody else. But it probably does mean they are smarter than they would be if they were not musicians.

Music training also helps improve certain memory capabilities outside of music. For example, musicians show improvements in auditory verbal memory and auditory attention, but not in visual memory or visual attention. This brings up the matter of learning styles: auditory, visual, or kinesthetic learning. Most people are visual learners, but to the best possible learners they need to develop all three styles. Music training should help their auditory learning style, especially under conditions where the sounds to be learned are embedded in conflicting sound stimuli, such as noisy rooms or learning a new language.

All fine and good, but how does this apply to the masses who are not musicians? Would listening to a lot of music help the brain? I doubt it, for listening does not make rigorous task demands on the brain. Would music training for non-musicians help the brain? Maybe, especially if the training occurred at a young age when the brain is ma-turing.

One study of children showed that fifteen months of intense music training induced structural changes in the primary auditory and primary motor areas. These structural changes were associated with improved auditory and motor skills, respectively. Other studies show children who are musically trained, compared with non-trained children, have a better vocabulary in their native language and a greater reading ability.  Pre-sumably, they would be better at learning other languages.

When and how much music training should be provided to children? Formal studies suggest that greatest benefit occurs if training begins before age 7. The benefits also cor-relate with the amount of music practice. However, much remains to be learned about effects of age and duration and nature of the music training.

Nina argues for more and better music education in the early grades of schools. She be-lieves music training may benefit academic achievement by improving learning skills and listening ability, especially in challenging listening environments, which are all too common in classrooms which are usually very noisy, despite research proving that classroom noise impairs learning. Noise not only creates problems of discerning salient sounds embedded in the over-all noise, but also creates a major distraction that impairs focused attention, information registration and memory consolidation.

I have summarized earlier research showing IQ in children improves when they are taught to have larger working memory capacity. Since working memory is apparently increased by music training, and music training also apparently enhances auditory learning, it seems like a no-brainer to suggest that more music training needs to occur in elementary school.

Source:
Kraus, N. and Chandrasekaran, B. 2010. Music training for the development of auditory skills. Nature Reviews. Neuroscience. 11: 500-505.

Multi-tasking and Memory, One More Time

I have talked about the problems of multi-tasking before. But this trend among youg people is so pernicious and damaging, I just have to bring it up again.

A whole new generation of multi-taskers is upon us. These young people know how to use cell phones, text messages, the Web, video games, IPods, and assorted other electronic gizmos, often at the same time. Sometimes, driving a car is thrown in for good measure (until an accident occurs).

I work with secondary school teachers, and most of them are in awe of these kids. I have seen teachers brag about how talented their own kids must be because they are such impressive multi-taskers. Increasingly, however, teachers come to realize that multi-tasking intereferes with learning. Some teachers are particularly upset with cell phones, which they try to ban, with little success. Talk about trying to take candy from a baby! In the old days, we kids tried to hide reading of comic books during class. Today, the game is to hide text messaging on cell phones. Ah, such is progress.

Multi-tasking is certainly a talent, but one that exacts a high price on learning. Formal brain research has shown that the brain can only do one thing at a time. Multi-tasking is accomplished much in the manner of "multiplexing," an engineering term denoting doing one thing for an instant, then another, and another, and finally returning to the next step of the first task. All this switching is distracting and interferes with memory formation and what memory reseasrchers call "consolidation" into lasting memory.

Memory consolidation is often prevented when one event follows too soon after an initial learning event. There is a whole theory about this, called the Interference Theory of Learning. Memory of initial learning events can be blocked if you try to learn two things at once. In fact, learning may be disrupted for both things.

In a recent test of this phenomenon, a group of 29 people (17 to 30 years of age) was trained to discriminate two sound pips that differed in length by a fraction of a second. In one group of subjects, the training occurred consecutively, which ordinarily produces some inefficiency with learning because the second task interferes with remembering the first. Moreover, results from another group of subjects revealed that when practice on the two tasks was interleaved in multi-task fashion, there was no learning on either condition.

Another recent study should get your attention: a group of study participants, divided into those that were heavy multi-taskers and those that multi-tasked only infrequently. All participants were probably at the higher end of general mental capabilities, given that they were Stanford college students. Each participant was tested in a series of thinking tests to check for any difference in the way the two types of people processed information and disciplined their attentiveness. Heavy multi-taskers were less able to sustain focus in the presence of distractions. The heavy multi-taskers performed worse even though their experience and presumed skill at multi-tasking should have made them more effective at these tasks. The heavy multi-taskers believed they were good at multi-tasking, when in fact they were bad at it.

Nor is intelligent thought likely to benefit from multi-tasking. Multi-tasking bombards working memory with scrambled and unfocused information and probably keeps the brain from learning how to optimize focus and orderly sequence thoughts. Several studies show that intelligence correlates with working memory capacity, which under the best of circumstances is limited. Working memory is the platform on which you think.Over-loading this small-capacity thinking platform just makes it harder to think straight.

So, now tell me again why multi-tasking is a good ability. While you are at it, try to convince me that it has no deleterious effect on ability to focus, sustain attention, and think.

Sources:

Banai, K. et al. 2010. Learning two things at once: differential constraints on the acquisition and consolidation of perceptual learning. Neuroscience. 165: 436-444.

Ophir, E., Nass, C. and Wagner, A. D. 2009. Cognitive control in media multitaskers. Proceedings of the National Academy of Science. Aug. 24. doi: 10.1073/pnas0903620106

Magnesium: a mineral you need and may lack

The only time I ever thought about magnesium,  before I became a scientist, was the summer I swept magnesium shavings off the floor at the Kaiser helicopter-engine factory. When I went to college, I learned that magnesium was an essential mineral in human and animal bodies. As a veterinary medical student, I learned that a magnesium deficiency caused "grass tetany" in cattle that ate lush, heavily fertilized grass growing especially in soils high in potassium or aluminum; these conditions reduce availability of magnesium.

Recently, a MIT scientist, Inna Slutsky reported a five year study showing that magnesium improved learning abilities, working memory and both short- and long-term memory in rats. The improvements were produced in both young and old rats. They fed rats a synthetic magnesium supplement, magnesium-L-threonate (MgT), which improved the ability of magnesium to get across the blood-brain barrier and into nerve cells.

How magnesium benefits brain function is probably related to the fact that magnesium is a cofactor for enzymes that convert adenosine triphosphate (ATP) to adenosine pyrophosphoric acid (ADP), with the subsequent release of energy. The brain is a real energy hog.

How much MgT would humans need to take is not known, but presumably somebody is working on that. The recommended daily amount of magnesium is 400 milligrams for men and 310 milligrams for women. It is estimated that only 32% of Americans get this amount in their diet. Primary food sources are green veggies, fruits, and certain nuts.  Traditional nutritional supplements are not a solution. The researchers found that the magnesium in common dietary supplements does not readily enter the brain.

A commercial product, when it becomes available, may not have been tested for safety (nutritional supplements are not government regulated), On the other hand, healthy kidneys are pretty good at getting rid of excess blood magnesium. The possibility of excess magnesium in the brain from use of MgT has not been investigated.

Source:
Slutsky, I. et al. 2009. Enhancement of learning and  memory by elevating brain magnesium. Neuron. 65 (2): 165-177.

Copyright, 2010, W.  R. Klemm

Can Exercise Help Kids Do Better in School?

Even when I was a kid, people said that being physically active could help you perform better in school. But this was mostly anecdotal, with very little research evidence. Now there is some evidence.

Charles Hillman and colleagues at the University of Illinois recently reported a study on the effects of exercise on cognitive function of 20 preadolescent children aged 9 to 10. They administered some stimulus discrimination tests and academic tests for reading, spelling and math. On one day, students were tested following a 20-minute resting period; on another day, students walked on a treadmill before testing. The exercise consisted of 20 min of treadmill exercise at 60% of estimated maximum heart rate. Mental function was then tested once heart rate returned to within 10% of pre-exercise levels. Results indicated improved performance on the tests following aerobic exercise relative to the resting session. Recordings of brain responses to stimuli suggested that the difference was attributable to improved attentiveness after exercise.

Note that this is just from a single aerobic exercise experience. How can that be beneficial? The most obvious explanation is that exercise generates more blood supply to the brain, but I don't know that this has been documented with MRI studies, for example. Actually, what is known is that exercise diverts blood to the muscles. The generally accepted view is that the body tightly regulates blood flow to the brain and that the brain always gets what it needs. Another possibility is that exercise relieves anxiety and stress, which are known to disrupt attentiveness and learning. Maybe the repetitive discipline of exercises like treadmill walking help entrain the brain into a more attentive mode. We need a study that compares tradmill walking with a different kind of exercise regimen (like a vigorous and competitive basketball game, for example).

As for what goes on in a typical school recess, I doubt that such activities as shooting marbles, gossiping, or whatever else goes on these days with kids at recess, really helps school work. Gym class might be another matter, but unfortunately many schools do not provide a meaningful gym class. Some of the authors' suggestions don't seem to be supported by this particular research. For example, they advocate:

• scheduling outdoor recess as a part of each school day (recess does not typically provide aerobic levels of exercise)

• offering formal physical education 150 minutes per week at the elementary level, 225 minutes at the secondary level (again, the beneficial effects likely come from aerobic levels of exercise, not just any exercise)

• encouraging classroom teachers to integrate physical activity into learning (this almost certainly will not be at aerobic levels of exercise.)

There is the also the issue of a continuing aerobic exercise program, which presumably could produce long-lasting beneficial effects in young children. My own prejudice is that schools and parents ought to get serious about requiring an aerobic exercise program for kids. It should not only improve the quality of school work but also help combat the epidemic of obesity and diabetes. One caveat: running to achieve aerobic levels of exercise may not be advisable in children. My own experience with jogging, for example, might have been great for my heart and brain, but I now have two artificial kness to show for it.

If exercise is so good for academic performance, why do varsity athletes generally make poorer grades than their classmates? Well, there are many other factors, of course. One prevailing attitude among athletes is that academics are less important to them than their sport. Their peers idolize athletic stars. Students who make all As are not considered heroes; they are considered nerds or otherwise abnormal. Athletes devote their time and energy to their sport, not school work.

Reference:

Hillman, C. H., et al. 2009. The effect of acute treadmill walking on cognitive control and academic achievement in preadolescent children. Neuroscience. 31;159(3):1044-54.

The Multi-tasking Scatterbrain

Nobody should be surprised that people who multi-task a lot are easily distracted. It could well be that they multi-task a lot because they are so distractable and less able to focus.

A recent rigorous study of this matter evaluated a group of study participants, divided into those that were heavy multi-taskers and those that multi-tasked only infrequently. All participants were probably at the higher end of general mental capabilities, given that they were Stanford college students. Each participant was tested in a series of thinking tests to check for any difference in the way the two types of people processed information and disciplined their attentiveness.
  
Heavy multi-taskers were less able to sustain focus in the presence of distractions. The researchers concluded that light multi-taskers "find it easier to attentionally focus on a single task in the face of distractions."

The study did not directly examine ability to memorize, but there surely must be a significant difference, given that memory formation is enhanced by sustained attentiveness and focus. There may be some undiscovered benefits of multi-tasking, but memorizing cannot be one of them.

Nor is intelligent thought likely to benefit from multi-tasking. Several studies that I have summarized elsewhere show that intelligence correlates with working memory capacity, which under the best of circumstances is limited and easily over-loaded by multiple simultaneous informational input.

The study did not test whether distractibility is a cause or a consequence of multi-tasking behavior. But the data clearly support the notion that people whose work or study requires concentration should not multi-task.
There is also the potential problem that frequent multi-tasking could be teaching the brain to become more distractible.

Source:

Ophir, E., Nass,  C., and Wagner, A. D. 2009. Cognitive control in media multitaskers. Proceedings National Academy of Science. 106 (37): 15583-15587. doi/10.1073/pnas.0903620106

Vitamin D: the wonder vitamin

Everybody knows that vitamin D is good for healthy bones. That is why they fortify milk with it. You may not know it is good for certain skin conditions, such is the one I have that appears every Winter when I don’t get enough sunlight, even though I live in Texas. Taking 2,000 IU vitamin D3 daily has stopped this problem. I read also that vitamin D stimulates the immune system. I am now surprised to learn it might be helpful for memory.

A research group in the United Kingdom, recognizing that many people are vitamin D deficient there because they don’t get much sunlight to help the skin generate vitamin D, pursued the question of why there are molecular receptors for vitamin D in the brain. What is that all about?

Some previous studies by other groups had shown vitamin D has protective effects on the brain and enhances its activity. Other studies had shown that low serum levels of the 25 (OH) form of vitamin D were associated with poor cognitive test performance among patients with mild Alzheimer disease, and a study of older adults revealed a positive correlation between 25(OH) D blood levels and scores on a mental function test.

This British study looked at a large population (3,133) of middle-aged and older men to evaluate the association between vitamin D levels and cognition. Specifically, the investigators tested blood levels of serum 25-hydroxyvitamin D in non-institutionalized European men, aged 40–79 years, and compared those levels with performance on three mental-function tests, one of which was a specific test of memory. High blood levels of vitamin D were associated with better performance on a test for analyzing complex visual images and a recognition memory test.

Studies like this are exceedingly complex, because there are many hard-to-control variables (the paper had more than 21 authors). Not surprisingly, depression, physical activity, physical performance, and smoking were all consistently associated with both cognitive test scores and 25(OH) D concentrations. Some mental-test scores, together with 25(OH)D levels, were additionally associated with drinking one or more alcoholic drink per week. Also, as expected, 25(OH) D levels varied markedly by season, peaking in the summer and reaching bottom in the winter.

After additional adjustments for age, education level, depression, basal metabolism, physical activity, physical performance, smoking, alcohol consumption, season, higher 25(OH) D concentrations were found to be associated more specifically with psychomotor speed and visual scanning.

Vitamin D exists in two common forms; vitamin D2 and D3. The form mainly produced in the skin and derived from natural dietary sources is vitamin D3, whereas the primary source of vitamin D2 is multivitamin preparations and some fortified foods. There have been conflicting reports as to whether vitamin D2 and vitamin D3 are equally effective at maintaining 25(OH) D levels,

Nobody knows why vitamin D affects brain function, but the existence of specific molecular receptors inside the nucleus of neurons cannot be dismissed. Possibilities include direct effects on promoting synthesis of the alertness-producing neurotransmitter, acetylcholine, or more indirect effects on intracellular calcium (calcium is a signaling molecule  in nerve cells). Other possible ways vitamin D might help brain function include its ability to stimulate synthesis of nerve growth factor.  Vitamin D is neuroprotective against stroke and, by its ability to attenuate neurotoxic insults, could have a major impact in preventing neurodegenerative diseases.  Vitamin D has the potential to increase glutathione which helps with detoxification and protection against free radical stress.

It is still an open question whether vitamin D helps memory. But I will keep taking my vitamin D3 to help my skin condition. Any benefit to my memory will be a much-appreciated bonus.


Source:

Lee, David M. et al. 2009. Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men. J. Neurol. Neurosurg. Psychiatry. 80:22-729. Doi: 10.1136/jnnp.2008.165720.

Resveratrol: the red wine magic chemical

I try not to get too excited about memory benefits of supplements. Certainly, I only have any level of faith in formal scientific studies that are well controlled and peer reviewed. I now think that resveratrol may be one of the few supplements that could have beneficial effects on brain function.

You no doubt have heard about the French red-wine drinkers, who are more healthy than they ought to be, given that they drink too much, exercise too little, and eat too much fat (as in goose liver and cheese). In trying to figure out how this can be, scientists have homed in on a major anti-inflammatory chemical in red wine, known as resveratrol. At this writing, over 2,000 scientific papers have been published. Don't worry, I am only going to tell you about a few. Most of the protective biological actions associated with resveratrol have been associated with its intrinsic radical scavenger properties and the protective effects that it confers on the heart.

Most of this research focuses on the compound's beneficial effects on heart and blood vessels and diabetes. The compound targets multiple enzymes in multiple organs. What I am summarizing here is recent research that suggests resveratrol might be beneficial for thinking ability in general and memory in particular.

A diabetes research group in Brazil recently reported a beneficial effect of resveratrol on diabetic rats. An earlier study by another group showed that resveratrol improved glucose metabolism and promoted longevity in diabetic mice. Other research groups had reported neuroprotective effects for resveratrol. The Brazil group focused on brain damage produced by diabetes. They induced diabetes in a group of rats, observing that this impaired their ability to memorize. The cause, as indicated by other studies, is that diabetes lowers the level of a major brain neurotransmitter that promotes alertness, attentiveness, and general cognitive function, acetylcholine. As an aside, the major treatment for Alzheimer's disease is Aricept, which enhances acetylcoline function. The Brazil group found that resveratrol suppressed activity of the enzyme that destroys acetylcholine, thus tending to restore more normal acetylcholine function. Resveratrol (in a modest rat dose of 10 and 20 mg/kg per day for 30 days) prevented the impairment of memory induced by diabetes.

Added to this finding about the brain enzyme, there are other reasons to think the anti-oxidant properties of resveratrol might be beneficial to the brain. The brain has more oxygen consumption than any bodily organ, about 20% of all the body's consumption. The brain therefore produces more free-radical damage, but the brain has especially low levels of antioxidant defense enzymes.

One recent study has revealed that resveratrol had protective effects against brain damage caused by a chemical that kills acetylcholine neurons. Injection of this toxin into the brain of rats impaired their memory performance in two kinds of maze tasks. The impairment was significantly reduced by repeated injection of resveratrol (10 and 20 mg/kg) pr day for 25 days, beginning four days before the toxin injection.
 
Another recent study examined the effect of dietary supplement on working memory in mice.  Groups of young adult and aged mice were put on a resveratrol-supplementd diet for four weeks before being injected with a cytokine to induce inflammation and accelerate aging. Mice were then tested for their ability to remember what they learned in a commonly used spatial memory task in a water maze. The dietary supplement significantly reduced memory impairment in the aged group, but not in the young adults. The lack of benefit in young adults was a little misleading, in that there was a "ceiling effect" in that the young adults, even though given cytosine, were already performing at near-mazimum levles. Cytosine had clear impairing effects in the contol aged mice, but much less so in the resveratrol-treated aged mice. In other words, aging makes an animal more susceptible to toxic chemicals, and thus there is more opportunity for any beneficial treatment to become manifest.

The memory studies have appeared only in the last year or so and are confined to laboratory animals. The beneficial effects may occur only in preventing damage, as with diabetes or other kinds of brain injury. Benefits may also be imperceptible in the young.

The open question is whether resveratrol will help cognitive function in humans, especially healthy humans.But you can be sure that research on humans will become intense. Positive memory-enhancing results in humans have alredy been published for consumption of blueberries, in which resveratrol is a major ingredient.

One of the first such randomized controlled trials of resveratrol effects on memory in normal older adults.has been launched in 2010 by Todd Manini and Steven Anton at the University of Florida's Institute of Aging.


What foods besides red grapes have resveratrol? The most likely other sources you would eat or drink are blueberries, cranberries, and peanuts. It is not likely that you could drink or eat enough of such substances to get enough resveratrol to do any good. Highly concentrated supplements are coming on the market. I haven't given up my two glasses of red wine each day, but I have started taking one of the supplements. I haven't seen any reports that these high doses of resveratrol are toxic.

Sources:

Abraham, J., and Johnson, R. W. 2009. Consuming a diet supplemented with resveratrol reduced infection-related neuroinflammation and deficits in working memory in aged mice. Rejuvenation research. 12 (6): 445-453.  DOI: 10.1089/rej.2009.0888

Harkiumar, K. B., and Aggarwal, B. B. 2008. Resveratrol.. A multitargeted agent fo age-associated chronic diseases. Cell Cycle 7:8, 1020-1035.

Kumar, A. et al. 2007. Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive imapirment and oxidative stress in rats. Pharmacology.79 (1): 17-26. DOI: 10.1159/000097511

Schmatz R, et al. 2009. Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2009 May 21;610(1-3):42-8. Epub 2009 Mar 19.