Forgetting May Be Part of the Process of Remembering



Whether drawing a mental blank on a new A.T.M. password, a favorite recipe or an old boyfriend, people have ample opportunity every day to curse their own forgetfulness. But forgetting is also a blessing, and researchers reported on Sunday that the ability to block certain memories reduces the demands on the brain when it is trying to recall something important.

The study, appearing in the journal Nature Neuroscience, is the first to record visual images of people’s brains as they suppress distracting memories. The more efficiently that study participants were tuning out irrelevant words during a word-memorization test, the sharper the drop in activity in areas of their brains involved in recollection. Accurate remembering became easier, in terms of the energy required.

Blocking out a distracting memory is something like ignoring an old (and perhaps distracting) acquaintance, experts say: it makes it that much harder to reconnect the next time around. But recent studies suggest that the brain plays favorites with memories in exactly this way, snubbing some to better capture others. A lightning memory, in short, is not so much a matter of capacity as it is of ruthless pruning — and the new study catches the trace of this process at it happens.

“We’ve argued for some time that forgetting is adaptive, that people actively inhibit some memories to facilitate mental focus,” as when they are trying to recall a friend’s new phone number or the location of a parking space, said Michael Anderson, a professor of cognitive neuroscience at the University of Oregon.

Dr. Anderson, who was not involved in the new research, said it was “ important new work because it maps out how this is happening neurobiologically.”

The researchers, neuroscientists at Stanford University, used a memory test intended to gauge how well people can recall studied words from among many similar words they have also seen. They had 20 young men and women, mostly Stanford students, view in quick succession a list of 240 word pairs. These included 40 capitalized words, each paired with six related, lower-case words: For example, “ATTIC-dust,” “ATTIC-junk,” and so on.

After studying the pairs, the participants were instructed to memorize three selected pairs from each of 20 capitalized words. In effect, this forced them to flag individual pairs, like ATTIC-dust, while trying to tune out very similar, distracting ones, like ATTIC-junk, for half of the total list of pairs they saw. They were told not to memorize any pairs from the other half of the list.

The researchers tested each person’s memory several times, and found that scores ranged from about 30 percent accuracy to 80 percent. They also measured how well each person suppressed the distracting word pairs, by comparing recall of those pairs with recall of the half of the list that was studied at first but later ignored. All the testing was done while participants were having their brains scanned by an M.R.I. machine.

“We found that the magnitude of the decrease in activity on M.R.I. was correlated to the amount of weakening of these competing memories” when the subjects were recalling the target words, said Brice Kuhl, a graduate student in the psychology department at Stanford and the study’s lead author. His co-authors were Anthony Wagner, Nicole Dudukovic and Itamar Kahn.

In particular, the researchers found that the more a study participant had suppressed the memory of distracting word pairs, the steeper the decrease in activity in a region of the brain called the anterior cingulated cortex. This neural area is especially active when people are engaged in weighing choices, say, in choosing which card to play in a game of hearts with two or more good options.

“From a broader point of view, given what we know about this area, the activity decreases as the task becomes more automatic, less demanding,” said Dr. Wagner, the senior author.

People blank on new passwords so often because of the distracting presence of old or other current passwords. The better the brain can block those distracting digits, the easier it can bring to mind the new ones, Dr. Wagner said.

This process is extremely familiar to people who have been immersed in a foreign language. In a recent study of native English speakers led by Dr. Anderson, researchers showed that beginners being drilled in Spanish were very slow to link pictures and words in English, compared with more bilingual participants. Those fluent in both languages had resolved the competition between the two tongues, inhibiting the encroachment, for example, of the word “zapato” on the word “shoe.”

In all, this research suggests that memories are more often crowded out than lost. An ideal memory improvement program, Dr. Anderson said, “would include a course on how to impair your memory. Your head is full of a surprising number of things that you don’t need to know.”

The findings should also reduce some of the anxiety surrounding “senior moments,” researchers say. Some names, numbers and details are hard to retrieve not because memory is faltering, but because it is functioning just as it should.

Cancer-drug refund scheme backed

A watchdog has endorsed a new scheme under which a bone marrow-cancer drug's manufacturers would refund the NHS if a patient did not respond to treatment.

The National Institute for Health and Clinical Excellence is recommending multiple myeloma patients in Wales and England should get Velcade on the NHS.

But it said the NHS should pay for the drug, which costs about £18,000 per patient, only when it worked.

The scheme, the first of its kind, was proposed by drugmaker Janssen-Cilag.

In clinical trials Velcade has been shown to slow, halt or even reverse the progression of multiple myeloma.

One trial was so promising, it was halted a year early.

Under the terms of the NICE recommendation, patients showing a full or partial response to the drug would be kept on it, with the treatment funded by the NHS.

However, patients showing minimal or no response would be taken off it - and the costs would be refunded by the manufacturer.

Patient access

The final decision on whether to put the refund scheme into practice rests with the manufacturer and the Department of Health, with final NICE guidance expected in October.

Andrew Dillon, NICE chief executive, said: "We are aware of the challenge that the NHS faces in ensuring that patients can access expensive, but potentially effective, treatments for life-threatening conditions such as cancer.

"If the drug's manufacturer accepts the proposals we are consulting on today, it will mean that when the drug works well the NHS pays but when it doesn't the manufacturer should bear the cost.

"All patients suitable for treatment will get the chance to see if the drug works well for them."

Initial draft NICE guidance recommended that Velcade should not be made widely available on the NHS.

However, the watchdog changed its mind following an appeal by the manufacturer - and its suggestion of a refund scheme.

Move welcomed

Eric Low, chief executive of the charity Myeloma UK, said: "We welcome the fact that these conversations have resulted in a creative way to ensure that this important cancer drug can be made available to patients.

"However, we now need to carefully consider the details of the draft recommendation as we have concerns that it may exclude some patients who could benefit."

Harpal Kumar, chief executive of the charity Cancer Research UK, praised NICE for recommending an "innovative approach".

"Pharmaceutical companies with confidence in the new treatments they are developing should not be frightened of schemes aimed at pricing treatments according to their benefit.

"Enabling the NHS to get value out of the money it spends on drugs will improve its ability to afford new treatments for cancer patients."

Gene therapy 'hope' on impotence

US scientists say they are closer to creating a gene therapy treatment for erectile dysfunction.

Human and animal trials suggest this could offer an alternative to current treatments for some patients, the American Society of Gene Therapy heard.

Researchers say gene therapy could be effective far longer than pills used just before sex, improving spontaneity.

The human trials involved injections into the penis and some experts queried whether men would choose this option.

New approach

Erectile dysfunction (ED), often referred to as impotence, is thought to affect about one in every 10 men in the UK.

ED collectively means an inability to get a good enough erection to achieve satisfactory intercourse, but it varies in severity.

There are many causes, and many effective treatments, including drugs like the three licensed in the UK - Viagra, Cialis and Levitra.

But not all types of ED respond well to medication - for example, ED caused by nerve damage following prostate cancer surgery.

US researchers are hopeful that for these patients, and those who experience side-effects with medication, gene therapy may be a good alternative.

Nerve damage

A University of Pittsburgh team, led by Dr Joseph Glorioso, tested an experimental gene therapy in rats with ED caused by nerve damage.

The gene therapy used comprised the herpes simplex virus as a carrier and either a gene called GDNF, or one called neurturin, which both help promote nerve growth.

Rats treated with the gene therapy showed significant recovery and were able to regain normal penile function after four weeks.

Meanwhile, scientists at Wake Forest University, with the help of Dr Arnold Melman from the Albert Einstein College of Medicine, have been conducting the first human study of gene therapy for ED.

Tests on 11 men with ED showed promising results. The treatment was well-tolerated, with few side effects, despite its delivery via an injection into the penis.

Although the primary goal of the study was to determine its safety, it also showed the therapy improved erectile function in some of the men.

Dr Melman said: "This is an exciting field of research because current treatments for men with erectile dysfunction, whether pills or minimally invasive therapies, must be used 'on demand', thereby reducing the spontaneity of the sexual act."

'Chronic disease'

The Wake Forest therapy works by inserting small pieces of DNA into cells to trigger the production of proteins which, in turn, help smooth muscle cells relax.

Relaxing the smooth muscle in the penis allows it to fill with blood and achieve an erection.

Dr Geoff Hackett, president of the British Society for Sexual Medicine, said the gene therapy might be appealing to some men for whom other treatments had failed, but predicted many men would be reluctant to have a shot in the penis.

He stressed that many men with ED also had underlying medical disease, such as high blood pressure, raised cholesterol or diabetes, and that this should also be treated.

And there is a good argument for treating ED as a chronic disease too, he said.

"Maybe men with ED should be taking a pill for it every day. If you take smaller amounts regularly, the side-effects are less," he explained.