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How Memory Works (and How to Preserve It)
Bret S. Stetka, MD, Felipe De Brigard, PhD
Medscape Medical News
February 13, 2015

Editor's Note: Over 5 million Americans currently have Alzheimer disease, the most common form of dementia.[1] One third of people older than 70 years without clinical dementia have memory loss severe enough to disrupt their daily routine.[2] Medscape recently spoke with memory expert Felipe De Brigard, PhD, an assistant professor in the Center for Cognitive Neuroscience at Duke University, about our evolving understanding of how memory works and what interventions are showing promise in preventing this incredibly prevalent condition.

Medscape: For decades, textbooks have taught us that the hippocampus is the brain's "memory center." But your work and that of others suggests that, like most mental functions, it's not that simple?that multiple brain regions are involved in memory, and that the hippocampus has functions beyond memory. What is the current state of the science into how we form memories?

Felipe De Brigard, PhD: One of the most important findings in the neuroscience of memory during the past century was the observation that the hippocampus is essential for our capacity to remember life episodes. After having his hippocampi surgically removed in 1957 to treat severe epilepsy, Henry Molaison?better known by his initials H.M.?appeared to be incapable of storing new experiences. People he met after the surgery were always strangers to him, and places he visited always felt new, as did every food he tried and every event he attended. This finding made it tempting to think of the hippocampus as the "memory center."

However, the reality is way more complex. First, H.M. didn't really lose all his memory. He could still remember old personal events, as well as all sorts of facts that he had not personally experienced?for example, world news from the past and geographic information. The hippocampus, then, did not seem to be that necessary for retrieving information already stored. It seemed essential only for storing or encoding such information.

Further studies on H.M. demonstrated that he was still able to learn new procedural information, as well as form new habits and acquire new skills. So not all memory encoding was compromised.

Moreover, further studies?not only with H.M., but also other patients and healthy individuals, using various neuroimaging techniques?showed that the hippocampus appeared to be critical for other cognitive tasks in addition to episodic recollection. We now know, for instance, that we need the hippocampus to imagine possible ways in which personal events could have occurred in the past or may occur in the future, particularly when such mental simulations require the recombination of past information into coherent spatial scenes. Further studies have shown that the hippocampus is required to process certain complex spatial and visual discrimination tasks, as well as certain kinds of linguistic operations.

In sum, to say that the hippocampus is the memory center is, at best, incomplete and, at worst, misleading.

How Are Memories Made?

Medscape: On a related note, can you summarize how memories form and are preserved?

Dr De Brigard: This is actually a difficult question, for which we only have the general shape of an answer, because many of its details are still unknown or unclear. Moreover, as it happens in neuroscience?and in all of biology, to be precise?these sorts of explanations involve many levels of description.

In the case of memory, we are talking abut changes that occur at the molecular level, the synaptic level, the cellular level, and even at the level of neural assembly and networks. That being said, when talking about memory formation and preservation, scientists usually separate three different stages: encoding, consolidation, and retrieval.

"Encoding" refers to the process in which information that is experienced becomes suitable to be stored in memory. For the case of episodic memories?ie, memories about particular personal events, the spatiotemporal contexts of which we can remember?this process requires one to rehearse in working memory the information to be stored.

The second stage is consolidation; this refers to the process by which the encoded information is stabilized, presumably into a more permanent "memory trace." Scientists normally distinguish two kinds of consolidation: synaptic consolidation, which are the changes at the synaptic level that occur in order for a particular memory to become stabilized, and systems consolidation, which is the involvement of the macrostructures of the brain that are required for the formation of memory traces.

Both kinds of consolidation interact; synaptic consolidation occurs in the neurons of the brain structures involved in system consolidation, although both processes differ in their timing. Consolidation at the systems level involves the interaction between the hippocampus and the sensory cortices of the brain where the encoded information was perceptually processed. Traditional views suggested that, somehow, the hippocampus was required to "record" the pattern of brain activation across the sensory cortex, to be reactivated at the time of retrieval.

According to the traditional view, the hippocampus was also supposed to be unnecessary for the retrieval of information, which is actually driven by the prefrontal cortex. (This helps to explain, for instance, why H.M. could remember remote episodes from his past despite having no hippocampi). Now, however, the hippocampus appears to be required at all stages?although this view remains controversial. Either way, what appears to be clear is that retrieval of stored information somehow requires the brain to reinstate the state it was in during encoding.

Medscape: What facets of memory decline with the more common neurodegenerative disorders, such as Alzheimer disease?

Dr De Brigard:
Different neurodegenerative disorders have different effects on memory. Alzheimer disease, for instance, tends to manifest initially with difficulties in episodic memory?particularly difficulties in encoding and retrieving relational information, such as information that involves connections between items, or between items and their context of encoding. [Editor's note: In other words, episodic memory allows us to recall specific events in our lives.] Other neurodegenerative diseases, such as Parkinson disease, that involve the deterioration of the substantia nigra in the midbrain are associated with difficulties in learning certain associations that require immediate feedback. Certain variants of frontotemporal dementias, such as semantic dementia, tend to be associated with difficulties in retrieving words or meanings, and are marked by speech impairment.

Sadly, many of these symptoms get much worse with time, which is why it is important to visit your doctor as soon as you start noticing them.

How Can Memory Be Preserved?

Medscape: What strategies, both pharmacologic and nonpharmacologic, have shown the most benefit in preserving memory?

Dr De Brigard:
To the best of my knowledge, we don't have solid data about pharmacologic interventions that help to prevent the normal decay of memory. However, data suggest that pharmacologic treatments help in persons with mild cognitive impairment or early dementia. We know that aerobic exercise, healthy living, and a rich and intellectual life are helpful in slowing down the progression of the memory impairments that come with age. Likewise, sleeping well and focusing one's attention on the task at hand?in other words, avoiding multitasking?help to consolidate information for future retrieval.

Our laboratory uses only behavioral and neuroimaging methods. However, a recent review by Maria Cotelli and collaborators[3] surveyed a large number of results of nonpharmacologic interventions in amnestic mild cognitive impairment and early Alzheimer disease. They found that some forms of memory intervention therapy?which may or may not include noninvasive brain stimulation?appear to improve performance in certain tasks, particularly when combined with pharmacologic therapy. My sense, though, is that much more research is needed to fully assess the extent to which these kinds of interventions can selectively improve memory performance in pathologic and nonpathologic aging.

Medscape: Some of the strongest data on delaying or preventing dementia involve exercise and dietary approaches. Can you speak specifically about these approaches?

Dr De Brigard:
As I mentioned in the previous question, a healthy lifestyle, both for the body and the mind, are the best strategies to keep our memory working well.

I also like to highlight the importance of attending to the information we want to encode. In today's world, people love to multitask. But, unfortunately, multitasking is very detrimental to memory consolidation. As I mentioned before, attention and working memory are of the essence for information to be encoded. If you divide your attention between two events, you fail to fully encode either of them; at best, you end up half-encoding both of them. When it comes to working on improving one's memory, it is important to remember all three stages?encoding, consolidation, and retrieval?because memory is not a single process.

Medscape: What about brain exercise programs or puzzles and crosswords?

Dr De Brigard:
From what I understand, the evidence is very clear that these sorts of "brain training" programs and apps neither make you smarter nor slow down the progression of memory or other cognitive declines. However, there is evidence that an active life?both physically and intellectually?does help to delay many symptoms of cognitive decline, and it may even make the slope of the decline less steep. This kind of lifestyle is what I'd recommend.
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