Working memory, long-term memory, and medial temporal lobe function

Abstract

Early studies of memory-impaired patients with medial temporal lobe (MTL) damage led to the view that the hippocampus and related MTL structures are involved in the formation of long-term memory and that immediate memory and working memory are independent of these structures. This traditional idea has recently been revisited. Impaired performance in patients with MTL lesions on tasks with short retention intervals, or no retention interval, and neuroimaging findings with similar tasks have been interpreted to mean that the MTL is sometimes needed for working memory and possibly even for visual perception itself. We present a reappraisal of this interpretation. Our main conclusion is that, if the material to be learned exceeds working memory capacity, if the material is difficult to rehearse, or if attention is diverted, performance depends on long-term memory even when the retention interval is brief. This fundamental notion is better captured by the terms subspan memory and supraspan memory than by the terms short-term memory and long-term memory. We propose methods for determining when performance on short-delay tasks must depend on long-term (supraspan) memory and suggest that MTL lesions impair performance only when immediate memory and working memory are insufficient to support performance. In neuroimaging studies, MTL activity during encoding is influenced by the memory load and correlates positively with long-term retention of the material that was presented. The most parsimonious and consistent interpretation of all the data is that subspan memoranda are supported by immediate memory and working memory and are independent of the MTL.

Figure 1.

Short-term retention of novel visual objects in memory-impaired patients with: (A) presumed MTL damage; (B,C) confirmed bilateral MTL damage; and (D) memory impairment from damage other than the MTL (AMN denotes amnesia). (A) Participants studied a detail of an abstract painting for 10 sec and then, after a delay of 10, 30, or 90 sec, decided which of two patterns they had seen previously. (B) Participants studied four kaleidoscope designs (1 sec each) with a 1-sec inter-stimulus interval. After a variable delay (0–2 sec, 6–10 sec, or 25–40 sec), they decided (yes or no) whether or not a test stimulus matched one of the images just presented. (C,D) Participants studied a monochrome abstract pattern and then, after unfilled delays of 0–5 sec or filled delays of 10–30 sec, indicated from an array of 14 patterns which pattern they had seen previously. Participants included four patients with confirmed MTL damage (C) and five different patients with mixed etiologies and memory impairment from damage other than the MTL (D). Unfortunately, two earlier reviews (Ranganath and Blumenfeld 2005; Graham et al. 2010) presented the data from the five patients with mixed etiologies (shown here in D) and mistakenly labeled the patients as MTL patients. (Panels A,B,D adapted from Ranganath and Blumenfeld 2005 [with permission from Elsevier © 2005]; panel C adapted from Holdstock et al. 2000 [with permission from Elsevier © 2000].)

Figure 2.

(A) Repeated (match) and manipulated (nonmatch) test trials were interleaved systematically among a sequence of scenes. Test trials appeared either immediately after the corresponding scene had been presented (lag 1), five trials later (lag 5), or nine trials later (lag 9). The task for each trial was to decide whether the scene had appeared earlier in the series, and then, critically (in the case of a “yes” response), whether any items in the scene had changed location. Note that, even for tests at a lag of 1, participants had to try to hold in mind many previous scenes because they did not know whether the memory question would concern the most recently presented scene or a scene presented up to nine items earlier. (B) Two trials illustrating a lag of 1. Each scene was presented for a total of 20 sec. The scene was first presented alone for 5 sec. For the next 6 sec, the scene was presented along with an orienting question that drew the participant's attention to the item in the scene that would be moved or not moved (e.g., “Is the urn directly under the mirror?” [No]). Participants were not told that the orienting question identified the item that would be relevant to the memory decision. (Whenever a scene was presented a second time, the answer to the orienting question was always the same as it was when the scene was first presented. Accordingly, the answer to the orienting question did not provide information about whether the scene had been altered or not.) For the remaining 9 sec of the trial, the scene was accompanied by the two memory questions (“Have you seen this scene before?” and [if yes] “Have any items changed location?”). Note that 14 sec elapsed (3 + 5 + 6 sec) between the removal of a novel scene and the first (Old/New) memory question for the next scene (from Jeneson et al. 2011b).

Figure 3.

Intact working memory and impaired long-term memory. (A) The number of trials needed to correctly repeat back a string of digits as a function of string length. MTL patient H.M. succeeded at six digits in his first try but could not succeed at repeating back seven digits even after 25 attempts with the same string. (B) The number of trials needed to learn the locations of different numbers of objects for MTL patient G.P. and controls. G.P. succeeded easily with one, two, and three objects but could not reproduce the locations of four objects, even after 10 attempts with the same display. Note that in both cases, the patients failed at about the point when controls began to make their first errors (adapted from Squire and Wixted 2011 [with permission from Annual Reviews]).

Figure 4.

(Left) Controls and patients with MTL lesions that included damage to the perirhinal cortex decided which of seven novel objects (“fribbles”), simultaneously presented, did not have an identical match (i.e., each array consisted of three pairs of identical fribbles and one odd fribble). There were three levels of feature ambiguity (i.e., overlap) between the stimuli. In the minimum condition, features were unique to each fribble such that a single feature distinguished the odd fribble from the pairs. In the intermediate and maximum conditions, the features overlapped such that only a conjunction of features distinguished the odd fribble from the pairs. In each panel, the odd fribble is in the center of the bottom row (panels adapted from Barense et al. 2007 [with permission from Elsevier © 2007]). (Right) The percent error score at each level of feature ambiguity for MTL patients and controls. Note that the patients were intact when the controls made no errors but were impaired in two conditions when the controls made errors (adapted from Barense et al. 2007 [with permission from Elsevier © 2007]).

Figure 5.

Activation in left hippocampus during encoding (white bars) and maintenance (black bars) of one, two, or four faces. Activation increased as memory load increased. Brackets show SEM (adapted from Axmacher et al. 2007 [with permission from the Society for Neuroscience © 2007]).

Figure 6.

(A) Activity in right hippocampus during one-back trials (white bars) and two-back trials (black bars) with simple and complex spatial images (see text). A similar pattern of activity was observed in right parahippocampal cortex. (B) Eight individuals took the same test as in the fMRI experiment. After a 10-min filled delay, they then took a surprise test of long-term retention for the stimuli presented during the task. The patterns in A and B are not identical, but it is noteworthy that the different conditions of learning (simple vs. complex material; one-back vs. two-back testing) had similar effects on hippocampal activity during learning and on long-term behavioral memory. Brackets show SEM (from Lee and Rudebeck 2010 [with permission from the Massachusetts Institute of Technology © 2010]).