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116 http://neurology.thelancet.com Vol 5 February 2006

A study that combines clinical andbasic research suggests that brainoestrogen deficiency may be a riskfactor for developing the neuro-pathology seen in Alzheimer’s disease(AD). Rena Li (Sun Health ResearchInstitute, Sun City, AZ, USA) andcolleagues report that oestrogenconcentrations in post-mortem brainsfrom women with AD are reduced

compared with matched controlswithout AD. Furthermore, amyloid-�(A�) plaque formation occurs earlier inoestrogen-deficient APP23 mice thanin control APP23 mice (a model forAD). “We plan to use this animalmodel to screen for drugs that canincrease the effect of brain oestrogenrather than peripheral oestrogen, anapproach that should avoid the

potential side-effects of hormonereplacement therapy [HRT]”, notes Li.

Women have a higher risk ofdeveloping AD than do men. Oneexplanation for this is that after themenopause the decline of gonadaloestrogen can make neurons moresusceptible to age-related neuro-degenerative processes. However,although some studies support this

Low brain oestrogen linked to Alzheimer’s disease risk

US scientists have shown that recallingmemories could depend on the brainreconstructing the type of corticalactivity that took place during theirformation (Science 2005; 310:1963–66), and that by tracking thebuild-up of these patterns an observercan actually predict the type of memoryan individual is about to recall.

“Our results show that when we tryto recall something we first reinstatethe general context of the memory weare looking for. After this we may worktowards the specifics by rebuilding therepresentations that were active duringthe original experience that we aretrying to retrieve”, explains Sean Polyn(Center for the Study of Brain, Mind,and Behavior, Princeton University,Princeton, NJ, USA). “In other words,we appear to start a memory searchusing a more general ‘category specific’

brain activity pattern to cue the recall ofspecific items.”

Polyn’s team used functional MRI(fMRI) to record the brain patternsproduced when human volunteersstudied three categories of 30 objects:pictures of famous people, famousplaces, and everyday items. Thevolunteers made judgments about thepictures (eg, how much they liked ordisliked the celebrities presented) tocreate recordable and recognisablemental contexts for their fMRIreadings. The researchers identifiedspecific activity patterns associatedwith the study of the three differentcategories.

“Some time later the volunteerswere given 3 min to recall what theyhad seen in these study lists in anyorder their memories came to them,and we checked to see whether therewere any recognisable brain activitypatterns associated with these recalls”,explains Polyn. Sure enough, thesame category-specific brain activitypatterns appeared during this recallphase, matching the categories towhich the to-be-recalled objectsand verbally communicated objectsbelonged.

“If the contextual reinstatement ofmemories really occurs, then thisshould take time as we search everdeeper levels of detail before reachingthe exact memory we are looking for”,explains Polyn. “So we looked at the

time lag between the appearance ofthe recognisable category-specificpatterns and the actual moment whenthe subjects vocalised their recalls. Wefound that the category-specific brainactivity appeared several secondsbefore subjects stated their recalledmemories; while we could not identifythe specific item that would berecalled, we could tell to whatcategory their next memory recall wasgoing to belong.”

The results also show how we mightforget things. If this top-down fashionof cueing for additional details finallyallows us to arrive at specific, recallableevents, weak cues might prevent usfrom reconstructing the necessarycortical activity, blocking our recall ofinformation even though it has beenproperly stored.

“This finding confirms long-heldideas about how memories are storedand retrieved”, remarked HowardEichenbaum (Boston University, MA,USA). “The brain has no specialwarehouse, file case, or hard disk justfor storing information. Instead, asEndel Tulving put it, ‘Memoryinvolves turning time’s arrow into aloop, mentally regenerating a pastexperience, and the act of recollectionoccurs as a result of reactivation of thesame areas that were engaged duringthe initial experience.’”

Adrian Burton

Recalling memories needs reconstruction of cortical activity

Human beings dredge up memories by a process of mental time travel

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