consolidation

The role of consolidation in memory

"Consolidation" is a term that is bandied about a lot in recent memory research. Here's my take on what it means.

Becoming a memory

Initially, information is thought to be encoded as patterns of neural activity — cells "talking" to each other. Later, the information is coded in more persistent molecular or structural formats (e.g., the formation of new synapses). It has been assumed that once this occurs, the memory is "fixed" — a permanent, unchanging, representation.

With new techniques, it has indeed become possible to observe these changes (you can see videos here). Researchers found that the changes to a cell that occurred in response to an initial stimulation lasted some three to five minutes and disappeared within five to 10 minutes. If the cell was stimulated four times over the course of an hour, however, the synapse would actually split and new synapses would form, producing a (presumably) permanent change.

Memory consolidation theory

The hypothesis that new memories consolidate slowly over time was proposed 100 years ago, and continues to guide memory research. In modern consolidation theory, it is assumed that new memories are initially 'labile' and sensitive to disruption before undergoing a series of processes (e.g., glutamate release, protein synthesis, neural growth and rearrangement) that render the memory representations progressively more stable. It is these processes that are generally referred to as “consolidation”.

Recently, however, the idea has been gaining support that stable representations can revert to a labile state on reactivation.

Memory as reconstruction

In a way, this is not surprising. We already have ample evidence that retrieval is a dynamic process during which new information merges with and modifies the existing representation — memory is now seen as reconstructive, rather than a simple replaying of stored information

Reconsolidation of memories

Researchers who have found evidence that supposedly stable representations have become labile again after reactivation, have called the process “reconsolidation”, and suggest that consolidation, rather than being a one-time event, occurs repeatedly every time the representation is activated.

This raises the question: does reconsolidation involve replacing the previously stable representation, or the establishment of a new representation, that coexists with the old?

Whether reconsolidation is the creating of a new representation, or the modifying of an old, is this something other than the reconstruction of memories as they are retrieved? In other words, is this recent research telling us something about consolidation (part of the encoding process), or something about reconstruction (part of the retrieval process)?

Hippocampus involved in memory consolidation

The principal player in memory consolidation research, in terms of brain regions, is the hippocampus. The hippocampus is involved in the recognition of place and the consolidation of contextual memories, and is part of a region called the medial temporal lobe (MTL), that also includes the perirhinal, parahippocampal,and entorhinal cortices. Lesions in the medial temporal lobe typically produce amnesia characterized by the disproportionate loss of recently acquired memories. This has been interpreted as evidence for a memory consolidation process.

Some research suggests that the hippocampus may participate only in consolidation processes lasting a few years. The entorhinal cortex, on the other hand, gives evidence of temporally graded changes extending up to 20 years, suggesting that it is this region that participates in memory consolidation over decades. The entorhinal cortex is damaged in the early stages of Alzheimer’s disease.

There is, however, some evidence that the hippocampus can be involved in older memories — perhaps when they are particularly vivid.

A recent idea that has been floated suggests that the entorhinal cortex, through which all information passes on its way to the hippocampus, handles “incremental learning” — learning that requires repeated experiences. “Episodic learning” — memories that are stored after only one occurrence — might be mainly stored in the hippocampus.

This may help explain the persistence of some vivid memories in the hippocampus. Memories of emotionally arousing events tend to be more vivid and to persist longer than do memories of neutral or trivial events, and are, moreover, more likely to require only a single experience.

Whether or not the hippocampus may retain some older memories, the evidence that some memories might be held in the hippocampus for several years, only to move on, as it were, to another region, is another challenge to a simple consolidation theory.

Memory more complex than we thought

So where does all this leave us? What is consolidation? Do memories reach a fixed state?

My own feeling is that, no, memories don't reach this fabled "cast in stone" state. Memories are subject to change every time they are activated (such activation doesn't have to bring the memory to your conscious awareness). But consolidation traditionally (and logically) refers to encoding processes. It is reasonable, and useful, to distinguish between:

  • the initial encoding, the "working memory" state, when new information is held precariously in shifting patterns of neural activity,
  • the later encoding processes, when the information is consolidated into a more permanent form with the growth of new connections between nerve cells,
  • the (possibly much) later retrieval processes, when the information is retrieved in, most probably, a new context, and is activated anew

I think that "reconsolidation" is a retrieval process rather than part of the encoding processes, but of course, if you admit retrieval as involving a return to the active state and a modification of the original representation in line with new associations, then the differences between retrieval and encoding become less evident.

When you add to this the possibility that memories might "move" from one area of the brain to another after a certain period of time (although it is likely that the triggering factor is not time per se), then you cast into disarray the whole concept of memories becoming stable.

Perhaps our best approach is to see memory as a series of processes, and consolidation as an agreed-upon (and possibly arbitrary) subset of those processes.

References: 
  • Frankland, P.W., O'Brien, C., Ohno, M., Kirkwood, A. & Silva, A.J. 2001. -CaMKII-dependent plasticity in the cortex is required for permanent memory. Nature, 411, 309-313.
  • Gluck, M.A., Meeter, M. & Myers, C.E. 2003. Computational models of the hippocampal region: linking incremental learning and episodic memory. Trends in Cognitive Sciences, 7 (6), 269-276.
  • Haist, F., Gore, J.B. & Mao, H. 2001. Consolidation of human memory over decades revealed by functional magnetic resonance imaging. Nature neuroscience, 4 (11), 1139-1145.
  • Kang, H., Sun, L.D., Atkins, C.M., Soderling, T.R., Wilson, M.A. & Tonegawa, S. (2001). An Important Role of Neural Activity-Dependent CaMKIV Signaling in the Consolidation of Long-Term Memory. Cell, 106, 771-783.
  • Lopez, J.C. 2000. Shaky memories in indelible ink. Nature Reviews Neuroscience, 1, 6-7.
  • Miller, R.R. & Matzel, L.D. 2000. Memory involves far more than 'consolidation'. Nature Reviews Neuroscience, 1, 214-216.
  • Slotnick, S.D., Moo, L.R., Kraut, M.A., Lesser, R.P. & Hart, J. Jr. 2002. Interactions between thalamic and cortical rhythms during semantic memory recall in human. Proc. Natl. Acad. Sci. U.S.A., 99, 6440-6443.
  • Spinney, L. 2002. Memory debate focuses on hippocampal role. BioMedNet News, 18 March 2002.
  • Wirth, S., Yanike, M., Frank, L.M., Smith, A.C., Brown, E.N. & Suzuki, W.A. 2003. Single Neurons in the Monkey Hippocampus and Learning of New Associations. Science, 300, 1578-1581.
  • Zeineh, M.M., Engel, S.A., Thompson, P.M. & Bookheimer, S.Y. 2003. Dynamics of the Hippocampus During Encoding and Retrieval of Face-Name Pairs, Science, 299, 577-580.

The most effective way of spacing your learning

We don’t deliberately practice our memories of events — not as a rule, anyway. But we don’t need to — because just living our life is sufficient to bring about the practice. We remember happy, or unpleasant, events to ourselves, and we recount our memories to other people. Some will become familiar stories that we re-tell again and again. But facts, the sort of information we learn in formal settings such as school and university, these are not something we tend to repeatedly recount to ourselves or others — not for pleasure anyway! (Unless you’re a teacher, and that’s part of the reason teaching is such a good way of learning!)

So, this is one of the big issues in learning: how to get the repetition we need to fix something in our brain. Simple repetition — the sort of drill we deplore in pre-modern schools — is not a great answer. Not simply because it’s boring, but because boring tasks are not particularly effective means of getting the brain to do things. Our brains respond much better to the surprising, the novel, the emotional, the interesting.

Teachers today are of course aware of this, and do try (or I hope they do!) to provide as much variety, and interest, as they can. But there is another aspect to repetition that is less widely understood, and that is the spacing between repetitions. Now the basic principle has been known for some time: spaced repetition is better than massed practice. But research has been somewhat lacking as to what constitutes the optimal spacing for learning. Studies have tended to use quite short intervals. But now a new study has finally given us something to work with.

For a start, the study was much bigger than the usual such study — over 1350 people took part — increasing the faith we can have in the findings. And, crucially, the interval between the initial learning session and the second review session ranged from several minutes to 3.5 months (specifically, 3 minutes; one day; 2 days; 4 days; 7 days; 11 days; 14 days; 21 days; 35 days; 70 days; 105 days). The time until test also covered more ground — up to nearly a year (more specifically: 7 days; 35 days; 70 days; 350 days). The initial learning session involved the participants learning 32 obscure facts to a criterion level of one perfect recall for each fact. The review session involved the participants being tested twice on each fact. They were then shown the correct answer. Testing included both a recall test and a recognition (multi-choice) test. The participants, by the way, ranged in age from 18 to 72 years, with an average of 34 (the study was done using the internet; so nice to get away from the usual undergraduate fodder).

So there we are, a very systematic study, made possible by having such a large pool of participants (the benefits of the internet!). What was found? Well, first of all, the benefits of spacing review were quite significant, much larger than had been seen in earlier research when shorter intervals had been used. Given a fixed amount of study time, the optimal gap, compared to no gap (i.e. 3 minutes), improved recall by 64% and recognition by 26%.

Secondly, at any given test delay, longer intervals between initial study session and review session first improved test performance, then gradually reduced it. In other words, there was an optimal interval between study and review. This optimal gap increased as test delay increased — that is, the longer you want to remember the information, the more you should spread the gap between study and review (this simplifies the situation of course — if you’re serious about study, you’re going to review it more than once!). So, for those remembering for a week, the optimal gap was one day; for remembering for a month, it was 11 days; for 2 months (70 days) it was 3 weeks, and similarly for remembering for a year. Extrapolating, it seems likely that if you’re wanting to remember information for several years, you should review it over several months.

Note that the general rule is absolute rather than relative: when measured as a proportion of test delay, the optimal gap declined from about 20 to 40% of a 1-week test delay to about 5 to 10% of a 1-year test delay. In other words, although the optimal gap between study and review increases as the length of time you want to remember for increases, the ratio of gap to that length of time will decrease. Which seems very commonsensical.

As the researchers point out (and as has been said before), “the interaction of gap and test delay implies that many educational practices are highly inefficient”, concentrating topics tightly into short periods of time. This practice is likely to give misleadingly high levels of immediate mastery (as shown in tests given at the end of this time) — performance which is unlikely to be sustained over longer periods of time.

It’s also worth noting that the costs of using a gap that is longer than the optimal gap are decidedly less than the costs of using a shorter gap — in other words, better to space your learning longer than too short.

This article first appeared in the Memory Key Newsletter for December 2008

The role of sleep in memory

Why do we need sleep?

A lot of theories have been thrown up over the years as to what we need sleep for (to keep us wandering out of our caves and being eaten by sabertooth tigers, is one of the more entertaining possibilities), but noone has yet been able to point to a specific function of the sleep state that would explain why we have it and why we need so much of it.

One of the things we do know is that young birds and mammals need as much as three times the amount of sleep as adult birds and mammals. It has been suspected that neuronal connections are remodeled during sleep, and this has recently been supported in a study using cats (Cats who were allowed to sleep for six hours after their vision was blocked in one eye for six hours, developed twice as many new or modified brain connections as those cats who were kept awake in a dark room for the six hours after the period of visual deprivation).

Certainly a number of studies have shown that animals and humans deprived of sleep do not perform well on memory tasks, and research has suggested that there may be a relationship between excessive daytime sleepiness (EDS) and cognitive deficits. A recent study has found that for seniors at least, EDS is an important risk factor for cognitive impairment.

The effect of sleep on memory and learning

Some memory tasks are more affected be sleep deprivation than others. A recent study, for example, found that recognition memory for faces was unaffected by people being deprived of sleep for 35 hours. However, while the sleep-deprived people remembered that the faces were familiar, they did have much more difficulty remembering in which of two sets of photos the faces had appeared. In other words, their memory for the context of the faces was significantly worse. (The selective effect of sleep on contextual memory is also supported in a recent mouse study – see below)

While large doses of caffeine reduced the feelings of sleepiness and improved the ability of the sleep-deprived subjects to remember which set the face had appeared in, the level of recall was still significantly below the level of the non-sleep-deprived subjects. (For you coffee addicts, no, the caffeine didn’t help the people who were not sleep-deprived).

Interestingly, sleep deprivation increased the subjects’ belief that they were right, especially when they were wrong. In this case, whether or not they had had caffeine made no difference.

In another series of experiments, the brains of sleep-deprived and rested participants were scanned while the participants performed complex cognitive tasks. In the first experiment, the task was an arithmetic task involving working memory. Sleep-deprived participants performed worse on this task, and the fMRI scan confirmed less activity in the prefrontal cortex for these participants. In the second experiment, the task involved verbal learning. Again, those sleep-deprived performed worse, but in this case, only a little, and the prefrontal areas of the brain remained active, while parietal lobe activity actually increased. However, activity in the left temporal lobe (a language-processing area) decreased. In the third study, participants were given a "divided-attention" task, in which they completed both an arithmetic and a verbal-learning task. Again, sleep-deprived participants showed poorer performance, depressed brain activation in the left temporal region and heightened activation in prefrontal and parietal regions. There was also increased activation in areas of the brain that are involved in sustained attention and error monitoring.

These results indicate that sleep deprivation affects different cognitive tasks in different ways, and also that parts of the brain are able to at least partially compensate for the effects of sleep deprivation.

Sleep deprivation mimics aging?

A report in the medical journal The Lancet, said that cutting back from the standard eight down to four hours of sleep each night produced striking changes in glucose tolerance and endocrine function that mimicked many of the hallmarks of aging. Dr Eve Van Cauter, professor of medicine at the University of Chicago and director of the study, said, "We suspect that chronic sleep loss may not only hasten the onset but could also increase the severity of age-related ailments such as diabetes, hypertension, obesity and memory loss."

Should we draw any conclusion from the finding that sleep deprivation increased the subjects’ belief that they were right, especially when they were wrong, and the finding that chronic sleep deprivation may mimic the hallmarks of aging? No, let us merely note that many people become more certain of their own opinions as they mature into wisdom.

Is sleep necessary to consolidate memories?

This is the big question, still being argued by the researchers. The weight of the evidence, however, seems to be coming down on the answer, yes, sleep is necessary to consolidate memories — although maybe for only some types of memory. Most of the research favoring sleep’s importance in consolidation has used procedural / skill memory — sequences of actions.

From this research, it does seem that it is the act of sleep itself, not simply the passage of time, that is critical to convert new memories into long-term memory codes.

Some of the debate in this area concerns the stage of sleep that may be necessary. The contenders are the deep "slow wave" sleep that occurs in the first half of the night, and "REM" (rapid eye movement) sleep (that occurs while you are dreaming). Experiments that have found sleep necessary for consolidation tend to support slow-wave sleep as the important part of the cycle, however REM sleep may be important for other types of memory processing.

Sleep studies cast light on the memory cycle

Two new studies provide support both for the theory that sleep is important for the consolidation of procedural memories, and the new theory of what I have termed the "memory life-cycle".

In the first study, 100 young adults (18 to 27) learned several different finger-tapping sequences. It was found that participants remembered the sequence even if they learned a second sequence 6 hours later, and performance on both sequences improved slightly after a night's sleep. However, if, on day 2, people who had learned one sequence were briefly retested on it and then trained on a new sequence, their performance on the first sequence plummeted on day 3. If the first sequence wasn't retested before learning the new sequence, they performed both sequences accurately on day 3.

In another study, 84 college students were trained to identify a series of similar-sounding words produced by a synthetic-speech machine. Participants who underwent training in the morning performed well in subsequent tests that morning, but tests later in the day showed that their word-recognition skill had declined. However, after a full night's sleep, they performed at their original levels. Participants trained in the evening performed just as well 24 hours later as people trained in the morning did. Since they went to bed shortly after training, those in the evening group didn't exhibit the temporary performance declines observed in the morning group.

On the basis of these studies, researchers identified three stages of memory processing: the first stage of memory — its stabilization — seems to take around six hours. During this period, the memory appears particularly vulnerable to being “lost”. The second stage of memory processing — consolidation — occurs during sleep. The third and final stage is the recall phase, when the memory is once again ready to be accessed and re-edited. (see my article on consolidation for more explanation of the processes of consolidation and re-consolidation)

The researchers made a useful analogy with creating a word-processing document on the computer. The first stage is when you hit “Save” and the computer files the document in your hard drive. On the computer, this takes seconds. The second stage is comparable to someone coming and tidying up your word document — reorganizing it and tightening it up.

The most surprising aspect of this research is the time it appears to take for memories to initially stabilize — seconds for the computer saving the document, but up to six hours for us!

See news reports on sleep's role in memory

See news reports on the effects of sleep deprivation

Added January 2012: a downloadable pdf with all articles and news reports pertaining to sleep, circadian rhythms, and meditation

References: 
  1. Drummond, S.P.A., Brown, G.G., Stricker, J.L., Buxton, R.B., Wong, E.C. & Gillin, J.C. 1999. Sleep deprivation-induced reduction in cortical functional response to serial subtraction. NeuroReport, 10 (18), 3745-3748.
  2. Drummond, S.P.A., Brown, G.G., Gillin, J.C., Stricker, J.L., Wong, E.C. & Buxton, R.B. 2000. Altered brain response to verbal learning following sleep deprivation. Nature, 403 (6770),655-7.
  3. Drummond, S.P.A., Gillin, J.C. & Brown, G.G. 2001. Increased cerebral response during a divided attention task following sleep deprivation. Journal of Sleep Research, 10 (2), 85-92.
  4. Fenn, K.M., Nusbaum, H.C. & Margoliash, D. 2003. Consolidation during sleep of perceptual learning of spoken language. Nature, 425, 614-616.
  5. Frank, M.G., Issa, N.P. & Stryker, M.P. 2001. Sleep Enhances Plasticity in the Developing Visual Cortex. Neuron, 30, 275-287.
  6. Graves, L.A., Heller, E.A., Pack, A.I. & Abel, T. 2003. Sleep Deprivation Selectively Impairs Memory Consolidation for Contextual Fear Conditioning. Learning & Memory, 10, 168-176.
  7. Harrison, Y. & Horne, J.A. 2000. Sleep loss and temporal memory. The Quarterly Journal of Experimental Psychology, 53A (1), 271-279. Research report
  8. Laureys, S., Peigneux, P., Perrin, F. & Maquet, P. 2002. Sleep and Motor Skill Learning. Neuron, 35, 5-7.
  9. Laureys, S., Peigneux, P., Phillips, C., Fuchs,S., Degueldre, C., Aerts, J., Del Fiore,G., Petiau, C., Luxen, A., Van der Linden, M., Cleeremans, A., Smith, C. & Maquet, P. (2001). Experience-dependent changes in cerebral functional connectivity during human rapid eye movement sleep [Letter to Neuroscience]. Neuroscience, 105 (3), 521-525.
  10. Mednick, S.C., Nakayama, K., Cantero, J.L., Atienza, M., Levin, A.A., Pathak, N. & Stickgold, R. 2002. The restorative effect of naps on perceptual deterioration. Nature Neuroscience, 5, 677-681.
  11. Ohayon,M.M.& Vecchierini,M.F. 2002. Daytime sleepiness and cognitive impairment in the elderly population. Archives of Internal Medicine, 162, 201-8.
  12. Siegel, J.M. 2001. The REM Sleep-Memory Consolidation Hypothesis. Science, 294 (5544), 1058-1063.
  13. Sirota, A., Csicsvari, J., Buhl, D. & Buzsáki, G. 2003. Communication between neocortex and hippocampus during sleep in rodents. Proc. Natl. Acad. Sci. USA, 100 (4), 2065-2069.
  14. Spiegel, K., Leproult, R. & Van Cauter, E. 1999. Impact of sleep debt on metabolic and endocrine function, The Lancet, 354 (9188), 1435-1439.
  15. Stickgold, R., Hobson, J.A., Fosse, R., Fosse, M. 2001. Sleep, Learning, and Dreams: Off-line Memory Reprocessing. Science, 294 (5544), 1052-1057.
  16. Stickgold, R., James, L. & Hobson, J.A. 2000. Visual discrimination learning requires sleep after training. Nature Neuroscience, 3, 1237-1238.
  17. Walker, M.P., Brakefield, T., Hobson, J.A. & Stickgold, R. 2003. Dissociable stages of human memory consolidation and reconsolidation. Nature, 425, 616-620.

Reactivate if you want to remember

action replay box

We know sleep helps consolidate memories. Now a new study sheds light on how your sleeping brain decides what’s worth keeping. The study found that when the information that makes up a memory has a high value—associated with, for example, making more money—the memory is more likely to be rehearsed and consolidated during sleep.

Cognitive decline in old age related to poorer sleep

A new study confirms the role slow-wave sleep plays in consolidating memories, and reveals that one reason for older adults’ memory problems may be the quality of their sleep.

Recent research has suggested that sleep problems might be a risk factor in developing Alzheimer’s, and in mild cognitive impairment. A new study adds to this gathering evidence by connecting reduced slow-wave sleep in older adults to brain atrophy and poorer learning.

The study involved 18 healthy young adults (mostly in their 20s) and 15 healthy older adults (mostly in their 70s). Participants learned 120 word- nonsense word pairs and were tested for recognition before going to bed. Their brain activity was recorded while they slept. Brain activity was also measured in the morning, when they were tested again on the word pairs.

As has been found previously, older adults showed markedly less slow-wave activity (both over the whole brain and specifically in the prefrontal cortex) than the younger adults. Again, as in previous studies, the biggest difference between young and older adults in terms of gray matter volume was found in the medial prefrontal cortex (mPFC). Moreover, significant differences were also found in the insula and posterior cingulate cortex. These regions, like the mPFC, have also been associated with the generation of slow waves.

When mPFC volume was taken into account, age no longer significantly predicted the extent of the decline in slow-wave activity — in other words, the decline in slow-wave activity appears to be due to the brain atrophy in the medial prefrontal cortex. Atrophy in other regions of the brain (precuneus, hippocampus, temporal lobe) was not associated with the decline in slow-wave activity when age was considered.

Older adults did significantly worse on the delayed recognition test than young adults. Performance on the immediate test did not predict performance on the delayed test. Moreover, the highest performers on the immediate test among the older adults performed at the same level as the lowest young adult performers — nevertheless, these older adults did worse the following day.

Slow-wave activity during sleep was significantly associated with performance on the next day’s test. Moreover, when slow-wave activity was taken into account, neither age nor mPFC atrophy significantly predicted test performance.

In other words, age relates to shrinkage of the prefrontal cortex, this shrinkage relates to a decline in slow-wave activity during sleep, and this decline in slow-wave sleep relates to poorer cognitive performance.

The findings confirm the importance of slow-wave brainwaves for memory consolidation.

All of this suggests that poorer sleep quality contributes significantly to age-related cognitive decline, and that efforts should be made to improve quality of sleep rather than just assuming lighter, more disturbed sleep is ‘natural’ in old age!

Reviewing alcohol's effects on normal sleep

A review on the immediate effects of alcohol on sleep has found that alcohol shortens the time it takes to fall asleep, increases deep sleep, and reduces REM sleep.

Because sleep is so important for memory and learning (and gathering evidence suggests sleep problems may play a significant role in age-related cognitive impairment), I thought I’d make quick note of a recent review bringing together all research on the immediate effects of alcohol on the sleep of healthy individuals.

The review found that alcohol in any amount reduces the time it takes to fall asleep, while greater amounts produce increasing amounts of deep sleep in the first half of the night. However, sleep is more disrupted in the second half. While increased deep sleep is generally good, there are two down sides here: first, it’s paired with sleep disruption in the second half of the night; second, those predisposed to problems such as sleepwalking or sleep apnea may be more vulnerable to them. (A comment from the researchers that makes me wonder if the relationship between deep sleep and slow-wave activity is more complicated than I realized.)

Additionally, at high doses of alcohol, REM sleep is significantly reduced in the first half, and overall. This may impair attention, memory, and motor skills. Moreover, at all doses, the first REM period is significantly delayed, producing less restful sleep.

The researchers conclude that, while alcohol may give the illusion of improving sleep, it is not in fact doing so.

Reference: 

[3269] Ebrahim, I. O., Shapiro C. M., Williams A. J., & Fenwick P. B. (2013).  Alcohol and Sleep I: Effects on Normal Sleep. Alcoholism: Clinical and Experimental Research. n/a - n/a.

Why learning gets harder as we get older

A mouse study shows that weakening unwanted or out-of-date connections is as important as making new connections, and that neurological changes as we age reduces our ability to weaken old connections.

A new study adds more support to the idea that the increasing difficulty in learning new information and skills that most of us experience as we age is not down to any difficulty in acquiring new information, but rests on the interference from all the old information.

Memory is about strengthening some connections and weakening others. A vital player in this process of synaptic plasticity is the NMDA receptor in the hippocampus. This glutamate receptor has two subunits (NR2A and NR2B), whose ratio changes as the brain develops. Children have higher ratios of NR2B, which lengthens the time neurons talk to each other, enabling them to make stronger connections, thus optimizing learning. After puberty, the ratio shifts, so there is more NR2A.

Of course, there are many other changes in the aging brain, so it’s been difficult to disentangle the effects of this changing ratio from other changes. This new study genetically modified mice to have more NR2A and less NR2B (reflecting the ratio typical of older humans), thus avoiding the other confounds.

To the researchers’ surprise, the mice were found to be still good at making strong connections (‘long-term potentiation’ - LTP), but instead had an impaired ability to weaken existing connections (‘long-term depression’ - LTD). This produces too much noise (bear in mind that each neuron averages 3,000 potential points of contact (i.e., synapses), and you will see the importance of turning down the noise!).

Interestingly, LTD responses were only abolished within a particular frequency range (3-5 Hz), and didn’t affect 1Hz-induced LTD (or 100Hz-induced LTP). Moreover, while the mice showed impaired long-term learning, their short-term memory was unaffected. The researchers suggest that these particular LTD responses are critical for ‘post-learning information sculpting’, which they suggest is a step (hitherto unknown) in the consolidation process. This step, they postulate, involves modifying the new information to fit in with existing networks of knowledge.

Previous work by these researchers has found that mice genetically modified to have an excess of NR2B became ‘super-learners’. Until now, the emphasis in learning and memory has always been on long-term potentiation, and the role (if any) of long-term depression has been much less clear. These results point to the importance of both these processes in sculpting learning and memory.

The findings also seem to fit in with the idea that a major cause of age-related cognitive decline is the failure to inhibit unwanted information, and confirm the importance of keeping your mind actively engaged and learning, because this ratio is also affected by experience.

Dopamine decline underlies episodic memory decline in old age

Findings supporting dopamine’s role in long-term episodic memory point to a decline in dopamine levels as part of the reason for cognitive decline in old age, and perhaps in Alzheimer’s.

The neurotransmitter dopamine is found throughout the brain and has been implicated in a number of cognitive processes, including memory. It is well-known, of course, that Parkinson's disease is characterized by low levels of dopamine, and is treated by raising dopamine levels.

A new study of older adults has now demonstrated the effect of dopamine on episodic memory. In the study, participants (aged 65-75) were shown black and white photos of indoor scenes and landscapes. The subsequent recognition test presented them with these photos mixed in with new ones, and required them to note which photos they had seen before. Half of the participants were first given Levodopa (‘L-dopa’), and half a placebo.

Recognition tests were given two and six hours after being shown the photos. There was no difference between the groups at the two-hour test, but at the six-hour test, those given L-dopa recognized up to 20% more photos than controls.

The failure to find a difference at the two-hour test was expected, if dopamine’s role is to help strengthen the memory code for long-term storage, which occurs after 4-6 hours.

Individual differences indicated that the ratio between the amount of Levodopa taken and body weight is key for an optimally effective dose.

The findings therefore suggest that at least part of the reason for the decline in episodic memory typically seen in older adults is caused by declining levels of dopamine.

Given that episodic memory is one of the first and greatest types of memory hit by Alzheimer’s, this finding also has implications for Alzheimer’s treatment.

Caffeine improves recognition of positive words

Another recent study also demonstrates, rather more obliquely, the benefits of dopamine. In this study, 200 mg of caffeine (equivalent to 2-3 cups of coffee), taken 30 minutes earlier by healthy young adults, was found to improve recognition of positive words, but had no effect on the processing of emotionally neutral or negative words. Positive words are consistently processed faster and more accurately than negative and neutral words.

Because caffeine is linked to an increase in dopamine transmission (an indirect effect, stemming from caffeine’s inhibitory effect on adenosine receptors), the researchers suggest that this effect of caffeine on positive words demonstrates that the processing advantage enjoyed by positive words is driven by the involvement of the dopaminergic system.

Rest briefly after learning

A small study with older adults provides support for the idea that learning is helped if you follow it with a few minutes ‘wakeful rest’.

Back in 2010, I briefly reported on a study suggesting that a few minutes of ‘quiet time’ could help you consolidate new information. A new study provides more support for this idea.

In the first experiment, 14 older adults (aged 61-81) were told a short story, with instructions to remember as many details as possible. Immediately afterward, they were asked to describe what happened in the story. Ten minutes then elapsed, during which they either rested quietly (with eyes closed in a darkened room), or played a spot-the-difference game on the computer (comparing pairs of pictures). This task was chosen because it was non-verbal and sufficiently different from the story task to not directly compete for cognitive resources.

This first learning phase was followed by five minutes of playing the spot-the-difference game (for all participants) and then a second learning phase, in which the process was repeated with a second story, and participants experienced the other activity during the delay period (e.g., rest if they had previously played the game).

Some 30 minutes after the first story presentation (15 minutes after the second), participants were unexpectedly asked to once again recall as many details as they could from the stories. A further recall test was also given one week later.

Recall on the first delayed test (at the end of both learning phases) was significantly better for stories that had been followed by wakeful resting rather than a game. While recall declined at the same rate for both story conditions, the benefits of wakeful resting were maintained at the test one week later.

In a second experiment, the researchers looked at whether these benefits would still occur if there was no repetition (i.e., no delayed recall test at the time, only at a week). Nineteen older adults (61-87) participated.

As expected, in the absence of the short-delay retrieval test, recall at a week was slightly diminished. Nevertheless, recall for stories that had been followed by rest was still significantly better than recall for stories followed by the game.

It’s worth noting that, in a post-session interview, only 3 participants (of the 33 total) reported thinking about the story during the period of wakeful rest. One participant fell asleep. Twelve participants reported thinking about the stories at least once during the week, but there was no difference between these participants’ scores and those who didn’t think about them.

These findings support the idea that a quiet period of reflection after new learning helps the memories be consolidated. While the absence of interfering information may underlie this, the researchers did select the game specifically to interfere as little as possible with the story task. Moreover, the use of the same task as a ‘filler’ between the two learning phases was also designed to equalize any interference it might engender.

The weight of the evidence, therefore, is that ten minutes of wakeful resting aided memory by providing the mental space in which to consolidate the memory. Moreover, the fact that so few participants actively thought about the stories during that rest indicates that such consolidation is automatic and doesn’t require deliberate rehearsal.

The study did, of course, only involve older adults. I hope we will see a larger study with a wider participant pool.

Benefits from fixed quiet points in the day

On my walk today, I listened to a downloaded interview from the On Being website. The interview was with ‘vocal magician and conductor’ Bobby McFerrin, and something he said early on in the interview really caught my attention.

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