Sleep-dependent memory consolidation and accelerated forgetting

Accelerated long-term forgetting (ALF) is a form of memory impairment in which learning and initial retention of information appear normal but subsequent forgetting is excessively rapid. ALF is most commonly associated with epilepsy and, in particular, a form of late-onset epilepsy called transient epileptic amnesia (TEA). ALF provides a novel opportunity to investigate post-encoding memory processes, such as consolidation. Sleep is implicated in the consolidation of memory in healthy people and a deficit in sleep-dependent memory consolidation has been proposed as an explanation for ALF. If this proposal were correct, then sleep would not benefit memory retention in people with ALF as much as in healthy people, and ALF might only be apparent when the retention interval contains sleep. To test this theory, we compared performance on a sleep-sensitive memory task over a night of sleep and a day of wakefulness. We found, contrary to the hypothesis, that sleep benefits memory retention in TEA patients with ALF and that this benefit is no smaller in magnitude than that seen in healthy controls. Indeed, the patients performed significantly more poorly than the controls only in the wake condition and not the sleep condition. Patients were matched to controls on learning rate, initial retention, and the effect of time of day on cognitive performance. These results indicate that ALF is not caused by a disruption of sleep-dependent memory consolidation. Instead, ALF may be due to an encoding abnormality that goes undetected on behavioural assessments of learning, or by a deficit in memory consolidation processes that are not sleep-dependent.

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(Image: Courtney Icenhour)

Forgetting Is Actively Regulated

In order to function properly, the human brain requires the ability not only to store but also to forget: Through memory loss, unnecessary information is deleted and the nervous system retains its plasticity. A disruption of this process can lead to serious mental disorders. Basel scientists have now discovered a molecular mechanism that actively regulates the process of forgetting. The renowned scientific journal “Cell” has published their results.

The human brain is build in such a way, that only necessary information is stored permanently - the rest is forgotten over time. However, so far it was not clear if this process was active or passive. Scientists from the transfaculty research platform Molecular and Cognitive Neurosciences (MCN) at the University of Basel have now found a molecule that actively regulates memory loss. The so-called musashi protein is responsible for the structure and function of the synaptic connections of the brain, the place where information is communicated from one neuron to the next.

Using olfactory conditioning, the researchers Attila Stetak and Nils Hadziselimovic first studied the learning abilities of genetically modified ringworms (C. elegans) that were lacking the musashi protein. The experiments showed that the worms exhibited the same learning skills as unmodified animals. However, with extended duration of the experiment, the scientists discovered that the mutants were able to remember the new information much better. In other words: The genetically modified worms lacking the musashi protein were less forgetful.

Forgetting is no coincidence
Further experiments showed that the protein inhibits the synthesis of molecules responsible for the stabilization of synaptic connections. This stabilization seems to play an important role in the process of learning and forgetting. The researchers identified two parallel mechanisms: One the one hand, the protein adducin stimulates the growth of synapses and therefore also helps to retain memory; on the other hand, the musashi protein actively inhibits the stabilization of these synapses and thus facilitates memory loss. Therefore, it is the balance between these two proteins that is crucial for the retention of memories.

Forgetting is thus not a passive but rather an active process and a disruption of this process may result in serious mental disorders. The musashi protein also has interesting implications for the development of drugs trying to prevent abnormal memory loss that occurs in diseases such as Alzheimer’s. Further studies on the therapeutic possibilities of this discovery will be done.

Forget about forgetting – The elderly know more and use it better

What happens to our cognitive abilities as we age? If your think our brains go into a steady decline, research reported this week in the Journal Topics in Cognitive Science may make you think again. The work, headed by Dr. Michael Ramscar of Tübingen University, takes a critical look at the measures usually thought to show that our cognitive abilities decline across adulthood. Instead of finding evidence of decline, the team discovered that most standard cognitive measures, which date back to the early twentieth century, are flawed. “The human brain works slower in old age,” says Ramscar, “but only because we have stored more information over time.”

Computers were trained, like humans, to read a certain amount each day, and to learn new things. When the researchers let a computer “read” only so much, its performance on cognitive tests resembled that of a young adult. But if the same computer was exposed to the experiences we might encounter over a lifetime – with reading simulated over decades – its performance now looked like that of an older adult. Often it was slower, but not because its processing capacity had declined. Rather, increased “experience” had caused the computer’s database to grow, giving it more data to process – which takes time.

Technology now allows researchers to make quantitative estimates of the number of words an adult can be expected to learn across a lifetime, enabling the Tübingen team to separate the challenge that increasing knowledge poses to memory from the actual performance of memory itself. “Imagine someone who knows two people’s birthdays and can recall them almost perfectly. Would you really want to say that person has a better memory than a person who knows the birthdays of 2000 people, but can ‘only’ match the right person to the right birthday nine times out of ten?” asks Ramscar.

The answer appears to be “no.” When Ramscar’s team trained their computer models on huge linguistic datasets, they found that standardized vocabulary tests, which are used to take account of the growth of knowledge in studies of ageing, massively underestimate the size of adult vocabularies. It takes computers longer to search databases of words as their sizes grow, which is hardly surprising but may have important implications for our understanding of age-related slowdowns. The researchers found that to get their computers to replicate human performance in word recognition tests across adulthood, they had to keep their capacities the same. “Forget about forgetting,” explained Tübingen researcher Peter Hendrix, “if I wanted to get the computer to look like an older adult, I had to keep all the words it learned in memory and let them compete for attention.”

The research shows that studies of the problems older people have with recalling names suffer from a similar blind spot: there is a far greater variety of given names today than there were two generations ago. This cultural shift toward greater name diversity means the number of different names anyone learns over their lifetime has increased dramatically. The work shows how this makes locating a name in memory far harder than it used to be. Even for computers.

Ramscar and his colleagues’ work provides more than an explanation of why, in the light of all the extra information they have to process, we might expect older brains to seem slower and more forgetful than younger brains. Their work also shows how changes in test performance that have been taken as evidence for declining cognitive abilities in fact demonstrates older adults’ greater mastery of the knowledge they have acquired.

Take “paired-associate learning,” a commonly used cognitive test that involves learning to connect words like “up” to “down” or “necktie” to “cracker” in memory. Using Big Data sets to quantify how often different words appear together in English, the Tuebingen team show that younger adults do better when asked to learn to pair “up” with “down” than “necktie” and “cracker” because “up” and “down” appear in close proximity to one another more frequently. However, whereas older adults also understand which words don’t usually go together, young adults notice this less. When the researchers examined performance on this test across a range of word pairs that go together more and less in English, they found older adult’s scores to be far more closely attuned to the actual information in hundreds of millions of words of English than their younger counterparts.

As Prof. Harald Baayen, who heads the Alexander von Humboldt Quantitative Linguistics research group where the work was carried out puts it, “If you think linguistic skill involves something like being able to choose one word given another, younger adults seem to do better in this task. But, of course, proper understanding of language involves more than this. You have also to not put plausible but wrong pairs of words together. The fact that older adults find nonsense pairs – but not connected pairs – harder to learn than young adults simply demonstrates older adults’ much better understanding of language. They have to make more of an effort to learn unrelated word pairs because, unlike the youngsters, they know a lot about which words don’t belong together.”

The Tübingen research conclude that we need different tests for the cognitive abilities of older people – taking into account the nature and amount of information our brains process. “The brains of older people do not get weak,” says Michael Ramscar. “On the contrary, they simply know more.”