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06/25/2009

Memories

Over the past ten years I’ve often drawn on memories from my past for material to write about in these columns. For example, I recall mentioning an experience in my childhood that I credit with spurring my interest in things scientific. I was only about 3 to 5 years old in Denver, Colorado, when an older neighbor, Clarence McComas, and I were out after dark and he had a metal rod of some kind. He hit the rod on a hard rock and I was awestruck by the sparks that were generated. I wondered how that could happen. At least that’s the way I remember the incident.

After reading an article by Kathleen McGowan titled "Out of the Past" in the July issue of Discover magazine, I’m rather upset. Could my memory be playing tricks upon me? I’m reasonably certain that Clarence McComas was real and why would I make up him hitting a rock with a metal rod? Was it really at night and, if so, what was I doing outside after dark? Were my parents negligent in allowing me out that late?

Why my sudden questioning of the accuracy of a memory that has stuck with me for some 75 years or so? In her article, McGowan talks about the work of researchers such as Karim Nader of McGill University. Nader stirred up the field of memory by the finding that memories are not the static kind of entity that had been thought for many years. I (hopefully, correctly) recall citing in a past column a demonstration by former Bell Labs worker John Hopfield, who became a renowned memory expert after leaving Bell. In a talk at Bell after he left for California, Hopfield likened the storage of a memory in the brain to writing on the edge of a stack of cards. If you hold a pack of playing cards together and write a number on the edge of a deck, you can read the number as long as you hold the deck together in the same position. Now take out a card, or even several cards, from the deck and you can still read the number.

Hopfield cited this as an example of how the brain can store a memory in a group of neurons or connections (synapses) among neurons. As you age, some of the neurons or connections may die or be disrupted but the memory is still "legible", so to speak. (I would be amazed if I haven’t also cited in an earlier column my proud achievement of actually finding a mistake in one of Hopfield’s equations published when we were both working on luminescence on gallium phosphide at Bell. Hopfield was one of the many who floated far above me in that ethereal world of theoretical physics at Bell Labs and it was a simple, completely unimportant mistake that he had made but it gave me great pleasure to have found it.)

Back to memory and Karim Nader. Nader was a young postdoc at New York University who was interested in the neurobiology of fear. While at NYU he attended a lecture by Eric Kandel, winner with two others of a Nobel Prize for their work related to the storing of memory. Kandel, using the sea slug nervous system as a model, studied in detail the way the brain forms a memory through electrical impulses and various biochemical reactions involving proteins that affect the structure and composition of the synapses. I won’t begin to try to explain, let alone understand, the complex nature of the reactions resulting in the storing of a memory. The bottom line is that the prevailing view was that a memory gets "consolidated" and once that has been accomplished the memory is a permanent sort of thing that is not easily changed. To me, it’s kind of like Hopfield’s example of writing on a deck of cards. You can fiddle by removing some cards but the memory remains intact.

A digression. Wanting to learn more about Kandel, I visited the Nobel Prize Web site and was fascinated by Kandel’s very long autobiographical account of his life. Kandel grew up in Austria and describes in detail the situation in Austria during the years when Hitler was leading up to his invasion and annexation of Austria. My own memory did not recall how enthusiastic a reception Hitler received in Austria when he took over the country. I imagine most of today’s young people may only know of the Austrian matter from the play or movie "The Sound of Music". It’s worth a visit to nobelprize.org if you’re interested in history of those times.

Back to our theme, Nader was inspired by Kandel’s lecture but wondered what happens when we recall a memory? Could recalling a memory somehow affect the memory and does it have to be "reconsolidated"? Nader had a hard time convincing his adviser that such questions were worth pursuing but the adviser, noted fear researcher Joseph LeDoux, gave in and the chase was on. At the time, in the early 1990s, there was a lot of interest in the news accounts about people recalling long-buried childhood memories of sexual abuse. There were doubts about whether some of the recalled memories were real or whether they were stimulated by suggestions of therapists that sexual abuse had occurred.

Various workers in the memory field showed that false memories could in effect be implanted. Individuals could be influenced into believing events had happened that never did occur. Having spent a good deal of time in Amsterdam when I was teaching courses there in the 1990s, I recall my concern when I read that a plane had crashed into an apartment building there in 1992. The next year, it seems that over half of the Dutch population surveyed had vivid memories of watching the plane crash on TV and could remember various details of the plane approaching and fire. The only problem was that there had been no video of the plane crashing! Obviously, memory can be manipulated.

In 1999, Nader did an experiment on rats that shook up the memory crowd. There’s a standard kind of test that the fear researchers used to study rats. You sound a particular tone followed by an electrical shock to a rat’s foot. Pretty soon, the clever rats realize that the tone doesn’t bode well for them and they freeze in place upon hearing the tone. Sound that tone again a couple weeks later and the rats still remember and freeze.

But Nader, when he sounded the tone two weeks later also simultaneously injected some of the rats with a chemical known to suppress the synapse processes that store a memory. That shouldn’t make any difference since the memory of the tone followed by a shock had already been stored, right? Wrong! The next time the rats heard the tone they did not freeze. The reaction among memory experts was electric. Nader’s experiment seemed to show that, when you recall a memory, you "unconsolidate" it and then reconsolidate it, not necessarily in the same form. Skepticism abounded.

 To me, it’s as if when you recall a memory you take that deck of cards with the writing on the edge of deck and somehow shuffle the cards. After you recall the memory the cards get put back together, possibly somewhat out of order or maybe even with some new writing that wasn’t there before.

When, in 2001, Nader presented his work at a neuroscience meeting there were over a thousand people in attendance, including Kandel himself. Nader managed to convince the skeptical audience that reconsolidation was worth a look. Since then other groups have confirmed that memory is indeed "unlocked" in the process of remembering and must be reconsolidated, with possible changes when you put the memory back in place. This means that every time you remember something and talk or write about it there’s a chance that in reconsolidating that memory you’re changing some detail or details. I was intrigued by the finding that some twins recall an event that happened to one of them as having happened to the other twin. A possible example: one twin had been pushed off a bike by a neighbor when the twins were age 8. Years later, each twin remembers that he was the one pushed.

Well, what’s going on today? This year Nader received an award for his work from the National Sciences and Engineering Research Council of Canada (NSERC). The NSERC Web site points out that memory reconsolidation has now been shown in animals ranging from fruit flies to chickens and humans. While the discovery of the malleability of unlocked memory has spurred much work on the chemistry and structure of synapses and the mechanisms of memory storage in the brain, there is another area of considerable promise, especially with all the returning veterans from Iraq and Afghanistan.

Post-Traumatic Stress Disorder (PSTD) is an all too common result for these veterans, who were under constant stress and fear of hidden explosive devices and have witnessed terrible incidents of buddies being killed or wounded. With PSTD, the soldier may experience recurring vivid memories or nightmares of these events accompanied by the associated fear or stress. One needn’t have been a soldier to have PSTD - accidents and crime situations can also leave victims with PSTD.

Memory reconsolidation offers hope for relieving the symptoms of PSTD. Roger Pitman at Harvard and Nader and clinical psychologist Alan Brunet at McGill have tried the following type of experimental treatment. Let’s say you have an accident victim who still has nightmares about the accident and/or is troubled by visions of the accident coming into his or her head at any time during the day. What the researchers do is to somehow recreate the accident by whatever means works - video, audio tape or by having the victim recall and tell of the incident verbally. At the same time, a common blood pressure medication, propranolol, is administered.

Propranolol has been found to partially block the reconsolidation of the fear component of the troubling memory. The memory of the accident is not erased, but the new memory has significantly less fear associated with recalling the accident. The McGill group has now treated at least 48 patients covering the gamut from soldiers to rape victims. By going through several sessions of reconsolidation treatment with repeated doses of propranolol, better results have been obtained. All of the patients have been helped; they remember the traumatic incidents but are not bothered as much by the memory of the incident.

Now the question is how long will the beneficial effects last? Is there another drug that will more effectively block reconsolidation of the fear factor? Can this type of reconsolidation treatment work to cure phobias or addictions? Both involve memories, pleasant ones for the addict, fearful ones for those with phobias such as fear of flying. Nader’s work with those traumatized rats has helped to open up a new field of medicine involving memory reconsolidation.

Finally, after finishing this column, I decided to check up on my own memory - did I actually mention my childhood experience with Clarence McComas in a previous column? I was gratified to find that our StocksandNews search engine turned up in the archives a column I posted exactly ten years and one month ago, on May 25, 1999. In that column, I said that I remembered clearly the blackness of the night sky and the stars shining brightly. Did I change that memory when I reconsolidated it? I can’t positively say today that I remember the stars; just the sparks in the darkness. In the highly unlikely event that I’m still alive ten years from now and again recall my childhood, will I have reconsolidated this memory with the stars back in the picture?

 Next column on July 9.

Allen F. Bortrum

 

 

 

 

 

 

 

 

 

 

 

 

 



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Dr. Bortrum

06/25/2009

Memories

Over the past ten years I’ve often drawn on memories from my past for material to write about in these columns. For example, I recall mentioning an experience in my childhood that I credit with spurring my interest in things scientific. I was only about 3 to 5 years old in Denver, Colorado, when an older neighbor, Clarence McComas, and I were out after dark and he had a metal rod of some kind. He hit the rod on a hard rock and I was awestruck by the sparks that were generated. I wondered how that could happen. At least that’s the way I remember the incident.

After reading an article by Kathleen McGowan titled "Out of the Past" in the July issue of Discover magazine, I’m rather upset. Could my memory be playing tricks upon me? I’m reasonably certain that Clarence McComas was real and why would I make up him hitting a rock with a metal rod? Was it really at night and, if so, what was I doing outside after dark? Were my parents negligent in allowing me out that late?

Why my sudden questioning of the accuracy of a memory that has stuck with me for some 75 years or so? In her article, McGowan talks about the work of researchers such as Karim Nader of McGill University. Nader stirred up the field of memory by the finding that memories are not the static kind of entity that had been thought for many years. I (hopefully, correctly) recall citing in a past column a demonstration by former Bell Labs worker John Hopfield, who became a renowned memory expert after leaving Bell. In a talk at Bell after he left for California, Hopfield likened the storage of a memory in the brain to writing on the edge of a stack of cards. If you hold a pack of playing cards together and write a number on the edge of a deck, you can read the number as long as you hold the deck together in the same position. Now take out a card, or even several cards, from the deck and you can still read the number.

Hopfield cited this as an example of how the brain can store a memory in a group of neurons or connections (synapses) among neurons. As you age, some of the neurons or connections may die or be disrupted but the memory is still "legible", so to speak. (I would be amazed if I haven’t also cited in an earlier column my proud achievement of actually finding a mistake in one of Hopfield’s equations published when we were both working on luminescence on gallium phosphide at Bell. Hopfield was one of the many who floated far above me in that ethereal world of theoretical physics at Bell Labs and it was a simple, completely unimportant mistake that he had made but it gave me great pleasure to have found it.)

Back to memory and Karim Nader. Nader was a young postdoc at New York University who was interested in the neurobiology of fear. While at NYU he attended a lecture by Eric Kandel, winner with two others of a Nobel Prize for their work related to the storing of memory. Kandel, using the sea slug nervous system as a model, studied in detail the way the brain forms a memory through electrical impulses and various biochemical reactions involving proteins that affect the structure and composition of the synapses. I won’t begin to try to explain, let alone understand, the complex nature of the reactions resulting in the storing of a memory. The bottom line is that the prevailing view was that a memory gets "consolidated" and once that has been accomplished the memory is a permanent sort of thing that is not easily changed. To me, it’s kind of like Hopfield’s example of writing on a deck of cards. You can fiddle by removing some cards but the memory remains intact.

A digression. Wanting to learn more about Kandel, I visited the Nobel Prize Web site and was fascinated by Kandel’s very long autobiographical account of his life. Kandel grew up in Austria and describes in detail the situation in Austria during the years when Hitler was leading up to his invasion and annexation of Austria. My own memory did not recall how enthusiastic a reception Hitler received in Austria when he took over the country. I imagine most of today’s young people may only know of the Austrian matter from the play or movie "The Sound of Music". It’s worth a visit to nobelprize.org if you’re interested in history of those times.

Back to our theme, Nader was inspired by Kandel’s lecture but wondered what happens when we recall a memory? Could recalling a memory somehow affect the memory and does it have to be "reconsolidated"? Nader had a hard time convincing his adviser that such questions were worth pursuing but the adviser, noted fear researcher Joseph LeDoux, gave in and the chase was on. At the time, in the early 1990s, there was a lot of interest in the news accounts about people recalling long-buried childhood memories of sexual abuse. There were doubts about whether some of the recalled memories were real or whether they were stimulated by suggestions of therapists that sexual abuse had occurred.

Various workers in the memory field showed that false memories could in effect be implanted. Individuals could be influenced into believing events had happened that never did occur. Having spent a good deal of time in Amsterdam when I was teaching courses there in the 1990s, I recall my concern when I read that a plane had crashed into an apartment building there in 1992. The next year, it seems that over half of the Dutch population surveyed had vivid memories of watching the plane crash on TV and could remember various details of the plane approaching and fire. The only problem was that there had been no video of the plane crashing! Obviously, memory can be manipulated.

In 1999, Nader did an experiment on rats that shook up the memory crowd. There’s a standard kind of test that the fear researchers used to study rats. You sound a particular tone followed by an electrical shock to a rat’s foot. Pretty soon, the clever rats realize that the tone doesn’t bode well for them and they freeze in place upon hearing the tone. Sound that tone again a couple weeks later and the rats still remember and freeze.

But Nader, when he sounded the tone two weeks later also simultaneously injected some of the rats with a chemical known to suppress the synapse processes that store a memory. That shouldn’t make any difference since the memory of the tone followed by a shock had already been stored, right? Wrong! The next time the rats heard the tone they did not freeze. The reaction among memory experts was electric. Nader’s experiment seemed to show that, when you recall a memory, you "unconsolidate" it and then reconsolidate it, not necessarily in the same form. Skepticism abounded.

 To me, it’s as if when you recall a memory you take that deck of cards with the writing on the edge of deck and somehow shuffle the cards. After you recall the memory the cards get put back together, possibly somewhat out of order or maybe even with some new writing that wasn’t there before.

When, in 2001, Nader presented his work at a neuroscience meeting there were over a thousand people in attendance, including Kandel himself. Nader managed to convince the skeptical audience that reconsolidation was worth a look. Since then other groups have confirmed that memory is indeed "unlocked" in the process of remembering and must be reconsolidated, with possible changes when you put the memory back in place. This means that every time you remember something and talk or write about it there’s a chance that in reconsolidating that memory you’re changing some detail or details. I was intrigued by the finding that some twins recall an event that happened to one of them as having happened to the other twin. A possible example: one twin had been pushed off a bike by a neighbor when the twins were age 8. Years later, each twin remembers that he was the one pushed.

Well, what’s going on today? This year Nader received an award for his work from the National Sciences and Engineering Research Council of Canada (NSERC). The NSERC Web site points out that memory reconsolidation has now been shown in animals ranging from fruit flies to chickens and humans. While the discovery of the malleability of unlocked memory has spurred much work on the chemistry and structure of synapses and the mechanisms of memory storage in the brain, there is another area of considerable promise, especially with all the returning veterans from Iraq and Afghanistan.

Post-Traumatic Stress Disorder (PSTD) is an all too common result for these veterans, who were under constant stress and fear of hidden explosive devices and have witnessed terrible incidents of buddies being killed or wounded. With PSTD, the soldier may experience recurring vivid memories or nightmares of these events accompanied by the associated fear or stress. One needn’t have been a soldier to have PSTD - accidents and crime situations can also leave victims with PSTD.

Memory reconsolidation offers hope for relieving the symptoms of PSTD. Roger Pitman at Harvard and Nader and clinical psychologist Alan Brunet at McGill have tried the following type of experimental treatment. Let’s say you have an accident victim who still has nightmares about the accident and/or is troubled by visions of the accident coming into his or her head at any time during the day. What the researchers do is to somehow recreate the accident by whatever means works - video, audio tape or by having the victim recall and tell of the incident verbally. At the same time, a common blood pressure medication, propranolol, is administered.

Propranolol has been found to partially block the reconsolidation of the fear component of the troubling memory. The memory of the accident is not erased, but the new memory has significantly less fear associated with recalling the accident. The McGill group has now treated at least 48 patients covering the gamut from soldiers to rape victims. By going through several sessions of reconsolidation treatment with repeated doses of propranolol, better results have been obtained. All of the patients have been helped; they remember the traumatic incidents but are not bothered as much by the memory of the incident.

Now the question is how long will the beneficial effects last? Is there another drug that will more effectively block reconsolidation of the fear factor? Can this type of reconsolidation treatment work to cure phobias or addictions? Both involve memories, pleasant ones for the addict, fearful ones for those with phobias such as fear of flying. Nader’s work with those traumatized rats has helped to open up a new field of medicine involving memory reconsolidation.

Finally, after finishing this column, I decided to check up on my own memory - did I actually mention my childhood experience with Clarence McComas in a previous column? I was gratified to find that our StocksandNews search engine turned up in the archives a column I posted exactly ten years and one month ago, on May 25, 1999. In that column, I said that I remembered clearly the blackness of the night sky and the stars shining brightly. Did I change that memory when I reconsolidated it? I can’t positively say today that I remember the stars; just the sparks in the darkness. In the highly unlikely event that I’m still alive ten years from now and again recall my childhood, will I have reconsolidated this memory with the stars back in the picture?

 Next column on July 9.

Allen F. Bortrum