Deep Within the Brain, a Mystery Called Memory

United Press International

In the inner labyrinth of the brain, under the folds and in the crevices, tucked in regions with functions scientists have yet to define, a neurochemical cocktail of cells and proteins has preserved the essence of virtually everything you have experienced.

Your first day of school? It's there. And those old shoes, the ones with holes in the soles and ragged laces, they are there too, along with facts, figures and a seemingly useless assortment of details.

Why is it possible to remember from decades past that a scalene triangle is the one in which all three angles are different, that the equilateral the one in which the angles are the same, yet not be able to recall what was said in conversation just two hours ago?

Memory.

Basically, it is the power to remember things or situations in the lives of all animals capable of perceiving their environment and storing information about it.

But scientists are finding that it is much more, especially in humans. It is a process involving millions of electrochemical communications that are relayed within billionths of a second between brain structures that only recently were found to play a role in what we know and recall.

Hopes to Map Brain

"If you opened the outer bark of the brain, opened the skull and peered down, you would be looking at the neocortex," explained Dr. James L. McGaugh, director of the Center for the Neurobiology of Learning and Memory at the University of California, Irvine.

McGaugh, who is attempting to discover the details of how and where memories are stored by studying memory-related structures and chemicals in the brains of rats, believes that scientists eventually will be able to produce a map, a geographical orientation to specific memory sites in the brain.

"The neocortex is the newest part of the brain in terms of evolution, and the general assumption is that human memory is stored in some way throughout the neocortex. But that remains a hypothesis. We really don't know yet where memories are stored," he said.

But McGaugh is on the trail.

He has found, in a series of studies with rats, that hormones released during a state of excitement can influence how well memory tasks are performed. And in similar investigations with humans at UC Irvine, states of excitement in test subjects tended to enhance how well events of a particular day were recalled, again suggesting the role of hormones in memory.

Hormones are proteins, chemical messengers released in small amounts by the endocrine glands and carried by the blood to target tissues. In the case of memory, hormones that may have one function elsewhere in the body theoretically work to enhance information encoded in the brain, new studies suggest.

Storage of Memories

"The hormones influence the storage of memories. You're going to store new information anyway, so the hormones influence the strength of the storage," McGaugh said.

The more stress, excitement, joy, anger or sadness associated with a certain situation theoretically influences how well that memory will be retained.

So it is no quirk that something studied under stress--theorems in math, dates for a history exam, places on a map--anything that enhances pressure under which the information is learned--increases the chances of its permanent storage, McGaugh said.

He identifies the key hormones--the neurochemical cocktail of memory storage--as adrenalin, vasopressin, the endorphins, epinephrine and norepinephrine, which he believes "have powerful effects on the storage of recent experience."

"They work on the parts of the brain involved in the processing of recently acquired information," he said. "The hormones themselves don't know anything at all. They're just catalysts with no content.

"Ultimately we will find out how these hormones act to strengthen memory at cellular sites, at the very brain cells in which changes have occurred to constitute a memory."

He said once the role of hormones at specific cellular sites has been identified, scientists will have a clear idea of where in the brain specific types of memories are stored.

McGaugh's work supports results of studies conducted at the National Institute of Mental Health in Bethesda, Md., where neuroscientists experimenting with monkeys have found that there are two pathways in the brain to memory storage.

The hormones McGaugh believes influence the retention of memories apparently are dispatched to specific structures in the brain before the memories are permanently stored in the neocortex.

"There are two parallel pathways involving the limbic system in the brain," said Dr. Mortimer Mishkin, chief of neuropsychology at NIMH. "These are called the hippocampal and the amygdalar pathways."

The hippocampus and amygdala are brain structures located in the medial part of the temporal lobe. They are among the structures that form the limbic system, the part of the brain associated with emotions.

"They appear to be involved in cognitive memory processes, memories that are available to the conscious or the memories of which we are aware," Mishkin explained.

"Learning new faces, tunes, places, tastes of foods; the names that go with faces or the words that go with tunes--these kinds of memories, information about the world, depend on the amygdalar pathway," Mishkin said.

"But there is a different kind of pathway in which the hippocampus is important. That is, associating any of these things--faces, tunes, whatever--with the places in the world where these things are to be found in your experience.

"You know where your desk is, where your umbrella is or where you parked your car. These kinds of memories take the hippocampal pathway."

Studies with human amnesia victims strongly implicate the importance of the hippocampus and amygdala in the formation of memories.

Dr. Brenda Milner of the Montreal Neurological Institute first reported more than 30 years ago in her work with an amnesia patient known only as H. M. that those brain structures may be crucial in retention of memories.

H. M., who since 1953 has been incapable of remembering anything new, lost most of his hippocampus and amygdala to a surgical procedure designed to cure his epilepsy. He has been able to learn new motor skills, such as hitting a tennis ball, or intellectual skills requiring trial and error, but all other new information has evaded him.

Milner's early studies are supported by new evidence from the Veterans Administration Medical Center in San Diego implicating the roles of deep brain structures in the formation of memories.

Dr. Stuart Zola-Morgan, a VA neuroscientist who studied an amnesia patient named R. B. for five years, found that the patient was incapable of remembering anything that occurred after an illness in which he lost oxygen supply to the brain.

Analysis of R. B.'s brain after his death showed that the hippocampus was damaged.

Laying Down of Memories

"The hippocampus apparently is involved in the laying down of memories," Zola-Morgan said. "And it may also hold the addresses for the storage areas in the brain for some old memories. We don't know that for certain. That's just a guess.

"We do know that animals and people who have damage to the hippocampus can learn new motor skills in a normal fashion.

"But declarative information, information for facts, dates, what you had for breakfast this morning, information that requires you to move back in temporal time and place, cannot be retained if the hippocampus is damaged."

Assault to the hippocampus can occur as a result of brain injury, surgery or such illnesses as stroke.

Zola-Morgan said he believes that R. B.'s case suggests that the hippocampus plays a role in the process by which new information is held and then parceled out to other areas of the brain for storage.

Because structures such as the hippocampus and amygdala only temporarily hold information before it is stored, scientists in other laboratories are searching for yet other clues that will lead to a better understanding of how and where memories are permanently stored in the brain.

Neuroscientists at USC and the Salk Institute in San Diego think that identifying changes that occur in the nerve cells of the brain will help provide answers about brain cell circuitry and how that circuitry is affected by storage of memories.

"There's a tremendous amount of plasticity in the neural circuitry of the brain," explained neurobiologist George P. Miljanich of the program in neural, informational and behavioral sciences at USC.

He explained that current theory holds that the brain's neurons, or nerve cells, make certain connections with each other when a memory is stored. But the system is malleable enough to permit countless alterations to accommodate all of the experiences that are stored as memories.

"Most researchers in this (field of study) presume that there is some change to the substrate of the brain," said neuro-anatomist David Amaral of the Salk Institute, explaining what occurs at the cellular level when new information is stored as a memory.

"One possibility is that a certain subset of synapses are strengthened in perhaps a competitive way and that strengthening forms the learned experience," Amaral said. "But just where memory is actually stored remains a paradox."

A synapse is the point at which a nerve signal jumps from one nerve cell to another.

"We can only presume that it is in the neocortex, but there is no empirical evidence at this point indicating that this is the case," he said.

Different Kinds of Memories

Miljanich said there are different kinds of memories: short-term, which degrade over seconds, minutes or hours, and long-term memories, which last for days, weeks, months and years. Theoretically, both depend upon the types of neural connections made and the importance the experience has to the person.

"If you learn a particular word in German and hear it only once, its definition will go into short-term memory and you might forget it by the next day.

"But if you continue to use the word over a period of time, then the continued experience of that word will cause it to become permanently stored in the brain," Miljanich said. "But what we don't know at this point is how they get there in permanent storage."

Mishkin of the mental health institute suggests that sensory centers throughout the brain work in concert to keep a memory intact and to recall it. Remembering a friend, he said, requires more than one area of the brain.

"You remember what that person looks like, what that person sounds like or a perfume," he said. "All of these factors relied on different areas of the brain when the person was first perceived, and it is believed that the same areas of the brain are stimulated when recalling that person as a memory."

He said that time can modify a memory or change it somewhat, or it can be lost altogether.

Mishkin said studies are also under way to develop an understanding in normal test subjects of the biochemistry of how memories are forgotten and why.

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