Finding Memory in the Brain

As I discussed in one of my posts, I have been watching the new show Dollhouse and it has made me curious about the cutting edge of neuroscience and whether it at all compares to the themes in the show.  The premise of Dollhouse is that people submit themselves, for money, to be a doll for a set number of years. This means that their memory will be temporarily wiped clean, leaving them with a flat, numb personality.  These “dolls” as the show calls them are about as personality-less as the plastic variety.  They are left with an essential memory that allows them to talk to one another, perform basic functions, and recall deep, unconscious memories such as always recognizing their handler, their personal body guard who accompanies them on their missions.  When the dolls are needed they are put in a chair that sends electromagnetic stimuli into their brain that imprints them with a specific personality.  They have access to this person’s memories and tendencies as well as any necessary skills like Kung Fu.  When this personality is no longer needed they are brought back to the chair and this personality and all of its memories are wiped clean.  It seems like I am getting far-fetched, but I was interested in studying memory for my final paper and doing so through the lens of what we know about the brain to make more informed guesses.  In this paper I want to focus on new studies that suggest we can erase and return memories. The studies that suggest we can both erase memories and get them back are extremely new, but they make a lot of sense and actually don’t seem that far-fetched based on what we have learned so far about the brain in this course.  The foundational concept in all of this is that memories never really go away, and this paper will explore this notion and its implications.
    It is actually possible to erase memories, sort of.  A study released in October 2008 has received a lot of publicity because it claims to be able to selectively remove the memories of mice (1).  The researchers discovered that the kinase enzyme Ca-MKII, which is really just a fancy name for a protein, ordinarily has a specific activity within the brain.  This protein has been shown to be central to learning and memory, but researchers were uncertain of how.  The researchers of this experiment wanted to discover when the protein was involved in the memory process. To figure this out the researchers manipulated the protein with a chemical inhibitor to make it stop doing its job, and they were able to do so in a way that did not interfere with the activity of other proteins in the brain.  Once they went through this complicated process they realized that the protein is central to the process of recalling memories.  This is how they got the idea that they would condition a mouse, putting in a chamber and playing a sound simultaneous to shocking mouse’s feet.  Eventually, every time the mouse entered the chamber it would freeze and it would have a similar visceral reaction to hearing the sound.  The next time they put the mouse in the chamber, but did not play a sound.  They did this because they knew the mouse remembered two conditions, the chamber and the sound.  By putting the mouse in the chamber alone they could isolate the variable of the chamber, and ensure that the mouse was recalling the conditioned memory of the chamber signaling a shock.  The researchers inhibited the protein in the mouse during this trial with the hopes that they could force the mouse to unlearn the memory of the chamber.  The experiment appeared to work. In the next trial when they put the mouse in the chamber it no longer responded to the chamber, and instead of freezing began wondering around. However, once the mouse heard the sound it froze again.  The researchers concluded that by inhibiting this protein involved in memory recall, and controlling what the mouse was recalling, they could successfully erase the mouse’s specific memory associating the chamber with an impending shock.  The researchers provide the metaphor for how the inhibited protein works: imagine the memory is inside a jar and that recalling it means unscrewing the lid; by altering the activity of the protein researchers are able to take the memory out of the jar. I read this I was intrigued, but also skeptical and confused.  I couldn’t imagine many possibilities for expanding this experiment because it is very difficult to control what memory is being recalled, and a memory being recalled can certainly never be an isolated piece of information. Recollection is extremely associational, and must be interconnected to multiple circuitries throughout the brain. How could we ever isolate a memory being recalled, and knowing that things are so interconnected how could we ever be sure the memory was really gone? First off, we could never actually do this experiment on humans because in order to alter the protein in this way involves genetically modifying it.  
    There is another way to think about erasing memory.  The memory can be “removed from the jar” or the jar can be lost altogether with no way to get to it.  The latter example is the type of memory loss seen in Alzheimer’s patients.  Alzheimer’s is a widely researched condition, and numerous recent studies have developed promising solutions to rebuild neural connections and create new neurons.  One study has found that stem cells can restore memories in damaged brains of mice suffering Alzheimer’s-like brain deterioration (2).  The researchers injected stem cells into the damaged and intact brains of mice and found that 4% of the stem cells became neurons, and that in the damaged brains the stem cells went right to work at the epicenter of memory, the hippocampus.  The hippocampus is one of the most studied parts of the brain because it has been shown to play a central role in the formation of new memories and the recollection of recent ones.  Alzheimer’s usually attacks the hippocampal region of the brain first, which is why these patients begin to have difficulty with day-to-day activities and recent memories as the first symptom (2)(3).  Another completely different approach has found that the cancer drug Bryostatin enables new connections to be made during the memory process. The study has been researching the effect of the drug on rats. Researchers found that the drug stimulates neural connections in the brain in the same way memory storage does naturally (4).  
    The research done to explore reconstructing neural connections in damaged brains and Alzheimer’s patients suggests that memory has to do with the synaptic connections in the brain, and the way everything is wired together. If neural pathways are rebuilt it is possible to restore memories. Memories never really go away, instead what goes away are the neural pathways granting access to the memory (5).  Indeed, this is probably a better description of what was going on in the experiment of modifying the memory recall protein in the brains of mice.  It is unlikely that the protein hooked onto the memory as it was being recalled and zapped it. Instead, the neural circuitry connecting formed in the process of recall was probably damaged somehow.  I am intrigued by the idea that a memory never goes away, and also by the idea that memories are stored throughout the brain.  
    Jeff Hawkins opens up this discussion on a theoretical level in his book On Intelligence (6).  In his exploration of how the neocortex works he emphasizes that the neocortex is a single system and that it is impossible to distinguish between its regions on any significant level.  The neocortex is therefore extremely adaptable as indicated by the interdependence of our sensory system. As we have discussed in the course, we are always relying on a combination of our senses, and a limitation with one sense is usually compensated. Some extreme examples include the ability to “see” patterns imprinted on the tongue or to read Braille using the part of the brain ordinarily responsible for vision.  It would not be surprising, knowing the adaptability of the neocortex in evaluating and storing everyday inputs, to learn that we store memories all over the brain.  For decades psychologists have realized that people have different “types” of memory.  For example, in one study done in 1988 damage to a man’s brain limited his ability to recall memories from oral cues, but not from visual cues (7).  When the spoken command to identify a dog was given the man was confused and could only describe it as an animal, but when shown a picture of a dog the man was able to describe characteristics, facts, and memories about dogs. This example is not entirely helpful for proving that memories exist throughout the brain, but it is a start.  Other studies have focused on the movement of memories throughout the brain as they age. Using the process previously discussed (1) of genetically reengineering the protein CaMkinase II in mice, researchers have been able to isolate its role in developing long-term memories. They have discovered that old memories reside primarily in the anterior cingulated region of the cortex.  The researchers discovered that there is active interaction between the hippocampus and the cortex, and that as memories age they leave the hippocampus and are stored in various regions of the cortex.  Another study confirms this finding that as memories age they move from the hippocampus toward the frontal cortex. Additionally, memories in the frontal cortex become more complex and involve a more widely distributed network of neurons.  This suggests that the process of moving our memories to the cortex involves interpreting our memory through the filter of all our previous experiences. This is manifested in the brain as the distribution of a memory throughout the cortex, as well as areas of the “old brain” in our motor functions and emotional triggers (6).  One article provided a helpful guess of what is going on with memory storage in the brain, stating “there are potentially as many different types of memory as there are types of information and input to remember” (10). A researcher attempting to locate the site of working memory in the brain also confirmed this inference that memory is everywhere: "I see working memory widely dispersed throughout the brain…There’s activity in the prefrontal area and the related parts of the sensory cortex, but also cells in the association cortex, the occipital areas, and other areas. There's a smaller percent of cells in these regions engaged at any given moment compared to those in the prefrontal cortex, but it suggests that working memory is widely distributed." (11).
    Returning to the question of whether Dollhouse is science or science fiction, I think the answer remains to be seen. Researchers have been making huge strides in the past few years to better locate the site of memories in the brain, but it seems improbable that there will be a clear understanding of where memories are stored and how in the near future.  Still, I am intrigued by the fact that we have memories that we can’t access, sometimes for a day, sometimes for a lifetime, and considering the specificity that must go into the connections making up the neural pathways.  In an instant I could smell something and be taken back to a memory I had not revisited for years.  It seems that the neocortex has an inexhaustible ability to store memories and information, but its fascinating that we have such minimal control over accessing them.  Often we need someone or something to stimulate memories.  Memory recall is an associative process that we often have little control over.   If we can’t even control our own memories, it seems extremely unlikely that the scientists in Dollhouse would be able to implant an alien memory into a person’s brain.  The premise of the science in Dollhouse assumes that memories are easily identifiable and retractable when in actuality they are entangled, contextual, and ever-changing.  






Works Cited

(1)    Saey, Tina Hessman. “Selective Memory”. Science News. Vol. 174 No. 11, November 22 2008. http://www.sciencenews.org/view/generic/id/37919/title/Selective_memory.
(2)    Sass, Regina. “Stem Cells Can Restore Memory in Brain Damaged Mice”.  Associated Content. November 3 2007. http://www.associatedcontent.com/article/436088/stem_cells_can_restore_memory_in_brain_pg2.html?cat=5
(3)    Hamilton, Jon. “Brain Study Indicates Why Some Memories Persist”. National Public Radio. Morning Edition.  January 29 2009. http://www.npr.org/templates/story/story.php?storyId=99958952
(4)    “Drug Found to Create New Connections in Brain, Restoring and Improving Memory”. Bio-Medicine. December 4 2007.  http://www.bio-medicine.org/medicine-news-1/Drug-Found-to-Create-New-Connections-in-Brain--Restoring-and-Improving-Memory-7577-1/
(5)    Mone, Gregory. “The Persistence of Memory”. MIT Technology Review. May/June 2009. http://www.technologyreview.com/article/22461/page3/
(6)    Hawkins, Jeff. On Intelligence. Holt Paperbacks: New York, 2004.
(7)    Rensberger, Boyce. “Tests Hint at Discrete Memory Systems; Brain-Damaged Patient’s Recall Differed Response to Sound, Sight”. The Washington Post. August 14 1988.
(8)    “Scientists Uncover How Brain Retrieves and Stores Older Memories”. University of Toronto. May 7 2004. http://www.nootropics.com/memory/anteriorcingulate-cortex.html
(9)    Costandi, Moheb. “Where Are Old Memories Stored in the Brain?” Scientific American. February 10 2009. http://www.scientificamerican.com/article.cfm?id=the-memory-trace&page=2
(10)    “How Memories Are Made in the Brain”. http://www.memoryzine.com/howmemoriesaremadeinbrain.html
(11)    Goleman, Daniel. “Biologists Find Site of Working Memory”. May 2 1995. http://www.nytimes.com/1995/05/02/science/biologists-find-site-of-working-memory.html?sec=&spon=&pagewanted=1