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New Treatments for Post-traumatic Stress

A new therapeutic approach is in sight for treatment of traumatic memories, including memories that cause PTSD. Two lines of memory research have converged to produce a treatment, and sometimes even a cure, for the most serious need to forget, PTSD. This may not be generally known or accepted, but at least two research groups have shown there is a blood pressure drug, propranolol, that helps us to forget overwhelmingly stressful memories and thus reduces the stress that goes with those memories. The latest treatment being investigated by some researchers is based on using a common blood pressure drug, propranolol, which has a side effect of blocking the re-consolidation of emotions associated with old memories when those memories are recalled.

One reason it is possible to forget or at least edit memories is that when even well-formed memories are recalled, they are put back on the scratch pad of working memory where they are accessible to “editing” and re-consolidation. As I explained in a  previous blog column, each time a memory is retrieved, it can get changed and re-stored in a different way.

While memories reside on the scratch pad of working memory, either for the first time or during any recall episode, they can be changed by drugs. Also relevant here is that memory consolidation is greatly influenced by the impact of the experience, which is magnified by strong emotion and the hormones such emotions release. During re-consolidation, under conditions of proper talk therapy, the emotional impact need not duplicate the original and a more benign version will be stored in memory.

The rationale for testing propranolol was developed in the seminal work by Roger Pitman and colleagues. They noted earlier studies showing that adrenalin (epinephrine), either injected or released naturally under stressful conditions, strengthens memory formation and fear conditioning. Adrenalin helps you to remember the bad event and hopefully you can avoid facing that threat again by being alert and prudent. Adrenaline acts on a class of molecular receptors called beta-adrenergic receptors. Certain drugs, among them propranolol, block beta receptors and thus might theoretically disrupt fear-induced memories. Several groups have confirmed that propranolol does impair fear-conditioned memory in both animals and humans.

Pitman’s group sought to extend this notion to PTSD in a pilot study of 41 patients. They conducted a double-blind, placebo-controlled study in which a single 40 mg oral dose of propranolol was given as soon as possible (within 6 hours) after a traumatic event experienced by patients who had been rushed to a hospital emergency room. Patients then continued the medication four times a day for 10 days followed by a 9 days when the dose was progressively reduced to zero.

One and three months later, patients returned for psychological testing aimed at measuring PTSD. At one month post trauma, the number of patients with PTSD in the propranolol group was almost half that of placebo controls. Not tested was the possibility that a larger dose, especially if given early or prior to the unpleasant experience, might be even more effective, since there probably is a narrow window of opportunity for the drug to be beneficial in impairing the consolidation of bad memories.

A similar result was obtained in a later study by Guillaume Vaiva and colleagues. Their hospital emergency room patients were given propranolol or a placebo 2-20 hours after experiencing an auto accident or physical assault. The patients tested were also selected for having abnormally fast heart rates, because propranolol is a common therapeutic for that condition. Propranolol was given in a dose of 40 mg three times daily for seven days, followed by gradual reduction to zero over 8-12 days.

Under the common situation where emotional trauma has already been consolidated, the obvious treatment approach for PTSD might be to have patients recall the traumatic event later while under the influence of propranolol. The idea is that during recall, the memory and its associated emotion have to be reconsolidated, and this is disrupted by the drug. Indeed, this idea is being hailed in some quarters as a possible major breakthrough in treatment of PTSD. Many positive results are being reported by physicians, and the Army is considering using this approach for combat-related PTSD. The National Institute of Mental Health is now recruiting patients for a Phase IV Clinical trial.

One obvious conclusion is that propranol might be a good PTSD preventive drug if given before an anticipated traumatic event. For example, I wonder if D.O.D. psychiatrists have thought about giving propranolol to combat troops just before they engage in battle.

Another issue that nobody seems to consider is the possibility that people on this kind of blood pressure medication might be suffering impairments of emotional memories that they don't want to lose. Does this drug cause a general dulling of emotions? Could it magnify the failing memories of the elderly?


Copyright 2010, W. R. Klemm. 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 memory.

Zombies Learn Too, But Not Well

I recently had a scholarly paper on free-will research published in a cognitive psychology journal. This experience has caused me to think about the role of free-will in learning and memory. Though it might seem like a stretch, how one approaches learning affects how well it is done. If you learn subconsciously, as in  being conditioned like Pavlov's dogs or trained seals, the learning is primitive and limited because it is hidden from consciousness. I call this zombie learning (anybody who has lectured to students has seen this happening throughout the room). On the other hand, when one consciously and freely wills to learn, he becomes engaged as an active learner. Such learning, being mediated in the consciousness, is available for refinement, expansion, application, and integration into other learning, past and future.

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.