Large Medial Temporal Lobe Lesions Research Articles

Spared Perception of the Structure of Scenes after Hippocampal Damage

To explore whether the hippocampus might be important for certain spatial operations in addition to its well-known role in memory, we administered two tasks in which participants judged whether objects embedded in scenes or whether scenes themselves could exist in 3-D space. Patients with damage limited to the hippocampus performed as well as controls in both tasks. A patient with large medial-temporal lobe lesions had a bias to judge objects in scenes and scenes themselves as possible, performing well with possible stimuli but poorly with impossible stimuli in both tasks. All patients were markedly impaired at remembering the tasks. The hippocampus appears not to be essential for judging the structural coherence of objects in scenes or the coherence of scenes. The findings conform to what is now a sizeable literature emphasizing the importance of the hippocampus for memory. We discuss our results in light of findings that other patients have sometimes been reported to be disadvantaged by spatial tasks like the ones studied here, despite less hippocampal damage and milder memory impairment.

Preserved capacity for scene construction and shifts in perspective after hippocampal lesions.

The hippocampus has long been recognized as important for the formation of long-term memory. Recent work has suggested that the hippocampus might also be important for certain kinds of spatial operations, as in constructing scenes, shifting perspective, or perceiving the geometry of scenes and their boundaries. We explored this proposal using a task similar to one used previously that related hippocampal activity to scenes and their boundaries. In our study, participants viewed scenes from above that displayed walls and towers. After viewing each scene, participants saw a scene from ground level and judged whether it was the same as or different from the scene just presented. The number of towers and walls in each scene was manipulated so that it was possible to assess how the structure of the scene affected performance. Patients with hippocampal lesions performed similarly to controls in all task conditions and had no special difficulty as a function of the layout of a scene and its boundaries. In contrast, a patient with large medial temporal lobe (MTL) lesions was impaired. Taken together, our findings suggest that the hippocampus is not needed for scene construction, shifts in perspective, or perceiving the geometry of scenes. The impairment associated with large MTL lesions may result from damage in or near parahippocampal cortex.

Spared perception of object geometry and object components after hippocampal damage

We tested the proposal that medial temporal lobe (MTL) structures support not just memory but also high-level object perception. In one task, participants decided whether a line drawing could represent an object in three-dimensional space and, in another task, they saw the components of an object and decided what object could be formed if the components were assembled. Patients with hippocampal lesions were intact, indicating that the hippocampus is not needed for perceiving the structural coherence of objects or appreciating the relations among object parts. Patients with large MTL lesions were moderately impaired, likely due to damage outside the MTL.

Map reading, navigating from maps, and the medial temporal lobe

We administered map-reading tasks in which participants navigated an array of marks on the floor by following paths on hand-held maps that made up to nine turns. The burden on memory was minimal because the map was always available. Nevertheless, because the map was held in a fixed position in relation to the body, spatial computations were continually needed to transform map coordinates into geographical coordinates as participants followed the maps. Patients with lesions limited to the hippocampus (n = 5) performed similar to controls at all path lengths (experiment 1). They were also intact at executing single moves to an adjacent location, even when trials began by facing in a direction that put the map coordinates and geographical coordinates into conflict (experiment 2). By contrast, one patient with large medial temporal lobe (MTL) lesions performed poorly overall in experiment 1 and poorly in experiment 2 when trials began by facing in the direction that placed the map coordinates and geographical coordinates in maximal conflict. Directly after testing, all patients were impaired at remembering factual details about the task. The findings suggest that the hippocampus is not needed to carry out the spatial computations needed for map reading and navigating from maps. The impairment in map reading associated with large MTL lesions may depend on damage in or near the parahippocampal cortex.

When recognition memory is independent of hippocampal function.

Hippocampal damage has been thought to result in broad memory impairment. Recent studies in humans, however, have raised the possibility that recognition memory for faces might be spared. In five experiments we investigated face recognition in patients with hippocampal lesions (H) or large medial temporal lobe (MTL) lesions, including patients where neurohistological information was available. Recognition of novel faces was unequivocally intact in H patients but only at a short retention interval. Recognition memory for words, buildings, inverted faces, and famous faces was impaired. For MTL patients, recognition memory was impaired for all materials and across all retention intervals. These results indicate that structures other than the hippocampus, perhaps the perirhinal cortex, can support face recognition memory in H patients under some conditions. The fact that the faces were novel when recognition memory was intact does not fully account for our findings. We propose that the role of the hippocampus in recognition memory is related to how recognition decisions are accomplished. In typical recognition tasks, participants proceed by forming an association between a study item and the study list, and the recognition decision is later made based on whether participants believe the item was on the study list. We suggest that face recognition is an exception to this principle and that, at short retention intervals, participants can make their recognition decisions without making explicit reference to the study list. Important features of faces that might make face recognition exceptional are that they are processed holistically and are difficult to verbally label.

Visual discrimination performance, memory, and medial temporal lobe function

We evaluated recent proposals that structures in the medial temporal lobe (MTL)--in particular, perirhinal cortex--support not just memory but certain kinds of perceptual abilities as well. Specifically, it has been suggested that the perirhinal cortex supports the perceptual abilities needed to accomplish visual discrimination performance when the stimuli have complex features and overlapping elements. However, the tasks that have been studied are quite challenging. Stimulus features must be held in working memory while attention shifts among the several parts of the display. When working memory capacity is exceeded, performance must depend on retrieval from long-term memory. Five patients with limited hippocampal lesions and one patient with large MTL lesions were asked to identify the unique object among twin pairs of objects that had a high degree of feature overlap and perceptual similarity. The patient groups performed similarly to controls when there were few objects and features in the displays, but exhibited abrupt declines in performance when the displays contained more objects and more features. Notably, the impairment was observed in memory-impaired patients with hippocampal lesions, not only in association with large MTL lesions that included perirhinal cortex. The pattern of performance suggested that patients encountered difficulty because working memory capacity was exceeded in the more difficult conditions such that performance needed to depend at least in part on long-term memory. Furthermore, when the burden on working memory was removed entirely, the patient with large MTL lesions performed as well as controls. Accordingly, we suggest that deficits on difficult discrimination tasks reported for patients with MTL lesions are due to impaired memory rather than impaired perception.

Visual Working Memory Capacity and the Medial Temporal Lobe

Patients with medial temporal lobe (MTL) damage are sometimes impaired at remembering visual information across delays as short as a few seconds. Such impairments could reflect either impaired visual working memory capacity or impaired long-term memory (because attention has been diverted or because working memory capacity has been exceeded). Using a standard change-detection task, we asked whether visual working memory capacity is intact or impaired after MTL damage. Five patients with hippocampal lesions and one patient with large MTL lesions saw an array of 1, 2, 3, 4, or 6 colored squares, followed after 3, 4, or 8 s by a second array where one of the colored squares was cued. The task was to decide whether the cued square had the same color as the corresponding square in the first array or a different color. At the 1 s delay typically used to assess working memory capacity, patients performed as well as controls at all array sizes. At the longer delays, patients performed as well as controls at small array sizes, thought to be within the capacity limit, and worse than controls at large array sizes, thought to exceed the capacity limit. The findings suggest that visual working memory capacity in humans is intact after damage to the MTL structures and that damage to these structures impairs performance only when visual working memory is insufficient to support performance.

Role of the hippocampus in remembering the past and imagining the future

It has been proposed that a core network of brain regions, including the hippocampus, supports both past remembering and future imagining. We investigated the importance of the hippocampus for these functions. Five patients with bilateral hippocampal damage and one patient with large medial temporal lobe lesions were tested for their ability to recount autobiographical episodes from the remote past, the recent past, and to imagine plausible episodes in the near future. The patients with hippocampal damage had intact remote autobiographical memory, modestly impaired recent memory, and an intact ability to imagine the future. The patient with large medial temporal lobe lesions had intact remote memory, markedly impaired recent memory, and also had an intact ability to imagine the future. The findings suggest that the capacity for imagining the future, like the capacity for remembering the remote past, is independent of the hippocampus.

New semantic learning in patients with large medial temporal lobe lesions

Two patients with large lesions of the medial temporal lobe were given four tests of semantic knowledge that could only have been acquired after the onset of their amnesia. In contrast to previous studies of postmorbid semantic learning, correct answers could be based on a simple, nonspecific sense of familiarity about single words, faces, or objects. According to recent computational models (for example, Norman and O'Reilly (2003) Psychol Rev 110:611-646), this characteristic should be optimal for detecting the kind of semantic learning that might be supported directly by the neocortex. Both patients exhibited some capacity for new learning, albeit at a level substantially below control performances. Notably, the correct answers appeared to reflect declarative memory. It was not the case that the correct answers simply popped out in some automatic way in the absence of any additional knowledge about the items. Rather, the few correct choices made by the patients tended to be accompanied by additional information about the chosen items, and the available knowledge appeared to be similar qualitatively to the kind of factual knowledge that healthy individuals gradually acquire over the years. The results are consistent with the idea that neocortical structures outside the medial temporal lobe are able to support some semantic learning, albeit to a very limited extent. Alternatively, the small amount of learning detected in the present study could depend on tissue within the posterior medial temporal lobe that remains intact in both patients.

The Fate of Old Memories after Medial Temporal Lobe Damage

Damage to the hippocampal region and related medial temporal lobe structures (perirhinal, entorhinal, and parahippocampal cortices) impairs new learning (anterograde amnesia) as well as memory for information that was acquired before the damage occurred (retrograde amnesia). We assessed retrograde amnesia with the Autobiographical Memory Interview (AMI) and with a news events test in six patients with damage limited primarily to the hippocampal region (H group) and two patients with large medial temporal lobe lesions (MTL group). On the news event test, the H group exhibited temporally limited retrograde amnesia covering approximately 5 years. On the same test, the MTL group exhibited an extensive retrograde amnesia covering decades. Nevertheless, performance was relatively spared for very remote time periods. On the AMI, all patients had intact remote autobiographical memory. Because our patients with hippocampal lesions, as well as our patients with large MTL lesions, performed normally on the AMI, patients who perform poorly on the same test presumably have damage beyond the hippocampus and related structures in the medial temporal lobe. The findings emphasize the difference in the extent of retrograde amnesia associated with hippocampal lesions and large MTL lesions.

Robust habit learning in the absence of awareness and independent of the medial temporal lobe

Habit memory is thought to involve slowly acquired associations between stimuli and responses and to depend on the basal ganglia. Habit memory has been well studied in experimental animals but is poorly understood in humans because of their strong tendency to acquire information as conscious (declarative) knowledge. Here we show that humans have a robust capacity for gradual trial-and-error learning that operates outside awareness for what is learned and independently of the medial temporal lobe. We tested two patients with large medial temporal lobe lesions and no capacity for declarative memory. Both patients gradually acquired a standard eight-pair object discrimination task over many weeks but at the start of each session could not describe the task, the instructions or the objects. The acquired knowledge was rigidly organized, and performance collapsed when the task format was altered.

Intact visual discrimination of complex and feature-ambiguous stimuli in the absence of perirhinal cortex

The perirhinal cortex is known to be important for memory, but there has recently been interest in the possibility that it might also be involved in visual perceptual functions. In four experiments, we assessed visual discrimination ability and visual discrimination learning in severely amnesic patients with large medial temporal lobe lesions that included complete lesions of perirhinal cortex. Experiment 1 tested complex visual object perception. Experiments 2a and 2b tested in two different ways the ability to discriminate between feature-ambiguous images, which was reported to be impaired in monkeys with perirhinal lesions. Experiment 3 involved images that were successfully discriminated in Experiment 2a and asked patients to learn across 20 trials which of the images had been designated as "correct." Patients performed as well as controls in Experiments 1, 2a, and 2b, but one of the patients had difficulty in Experiment 3 when the task required remembering from trial to trial which image was "correct." These findings indicate that perirhinal cortex is not needed for visual perception across a wide range of visual perceptual tasks.

Failure to acquire new semantic knowledge in patients with large medial temporal lobe lesions.

We examined new semantic learning in two profoundly amnesic patients (E.P. and G.P.) whose lesions involve virtually the entire medial temporal lobe (MTL) bilaterally. The patients were given five tests of semantic knowledge for information that could only have been acquired after the onset of their amnesia in 1992 and 1987, respectively. Age-matched and education-matched controls (n = 8) were also tested. On tests of recall, E.P. and G.P. each scored 10% correct on a test of 20 easy factual questions (controls = 90%), 2% and 4% correct on 55 questions about news events (controls = 85%), and 0% and 4% correct on a test of 24 famous faces. On three tests of recognition memory for this same material, the patients scored at chance levels. Similarly, the patients were unable to judge whether persons who had been famous for many decades were still living or had died during the past 10 years (E.P. = 53%; G.P. = 50%; controls = 73%; chance = 50%). Lastly, neither patient E.P. nor patient G.P. could draw an accurate floor plan of his current residence, despite having lived there for 10 years and 1 year, respectively. The results demonstrate that the capacity for new semantic learning can be absent, or nearly absent, when there is virtually complete damage to the MTL bilaterally. Accordingly, the results raise the possibility that the acquisition of conscious (declarative) knowledge about the world cannot be supported by structures outside the MTL, even with extended exposure. Published 2004 Wiley-Liss, Inc.

The anatomy of semantic knowledge: medial vs. lateral temporal lobe.

Semantic knowledge (e.g., long-established knowledge about objects, facts, and word meanings) is known to be severely impaired by damage to the anterolateral temporal lobe. For example, patients with semantic dementia have prominent atrophy in anterolateral temporal cortex and also have significant damage within the medial aspect of the temporal lobe. However, there is uncertainty about the contribution of medial temporal lobe damage, including perirhinal cortex damage, to impaired semantic knowledge. Drawing largely on published material from multiple sources, we compared the performance of severely amnesic patients with large medial temporal lobe lesions and patients with semantic dementia on nine tests of semantic knowledge and two tests of new learning ability. On the tests of semantic knowledge, the amnesic patients performed markedly better than the patients with semantic dementia. By contrast, on the tests of new learning, the patients with semantic dementia performed markedly better than the amnesic patients. We conclude that medial temporal lobe damage impairs the formation of declarative memory, and that semantic knowledge is impaired to the extent that damage extends laterally in the temporal lobe. Reports that the extent of atrophy in perirhinal cortex correlated with the severity of impaired semantic knowledge may be understood by supposing that the extent of damage in many temporal lobe areas is intercorrelated in this progressive disease, and that the extent of atrophy in perirhinal cortex is a proxy for the overall severity of dementia.

Semantic knowledge in patient H.M. and other patients with bilateral medial and lateral temporal lobe lesions

We investigated the effects of damage to the medial temporal lobe (MTL) and anterolateral temporal cortex on semantic knowledge. We studied eight male controls, two patients with lesions limited to the hippocampal formation, three postencephalitic patients with extensive MTL lesions and variable damage to the lateral temporal cortex, and patient H.M. (whose lesion is limited mostly to the MTL, but who also has minimal damage to the anterolateral cortex). On 13 tests of semantic memory, patients with lesions limited to the hippocampal formation performed similarly to controls. Postencephalitic patients were mildly to moderately impaired on most tests. Patient H.M.'s performance was impaired on only a few tests and was less severely impaired overall than the three postencephalitic patients. A ranking of test scores showed a direct relationship between impairment and the extent of damage to lateral temporal cortex. These findings, and related findings from other studies, point to the importance of anterolateral temporal cortex for semantic knowledge. Patient H.M. performed uniquely in certain respects. For example, when providing definitions of objects, he made many grammatical errors. In contrast, the other patients with large MTL lesions made no more errors than those made by controls. Considering that H.M.'s lesion, both medially and laterally, is less extensive than the lesions in these other patients, it appears unlikely that his shortcomings in language production are related to his temporal lobe lesion.

Contrasting Effects on Discrimination Learning after Hippocampal Lesions and Conjoint Hippocampal–Caudate Lesions in Monkeys

Eighteen monkeys with lesions of the hippocampal region (the hippocampus proper, the dentate gyrus, and the subiculum) made by an ischemic procedure, radio frequency, or ibotenic acid were tested on a simple, two-choice object discrimination learning task that has been shown to be sensitive to large lesions of the medial temporal lobe. The monkeys were also tested on two other discrimination tasks (pattern discrimination and eight-pair concurrent discrimination) that can be learned normally by monkeys with large medial temporal lobe lesions. All of the lesion groups were impaired at learning the simple object discrimination task. Seven of the monkeys who had sustained damage to the hippocampal region also sustained damage to the tail of the caudate nucleus. These seven monkeys, but not the other 11 monkeys with hippocampal lesions, were impaired on pattern discrimination and concurrent discrimination learning. The results suggest that the hippocampal region is important for learning easy, two-choice discriminations, whereas the caudate nucleus is necessary for the normal learning of more difficult, gradually acquired discrimination tasks. The findings support the distinction between declarative memory, which depends on the hippocampus and related medial temporal lobe structures, and habit learning, which depends on the caudate nucleus.

Severity of memory impairment in monkeys as a function of locus and extent of damage within the medial temporal lobe memory system.

During the past decade, work with monkeys has helped identify the structures in the medial temporal lobe that are important for memory: the hippocampal region (including the hippocampus proper, the dentate gyrus, and the subicular complex) and adjacent cortical areas that are anatomically linked to the hippocampus, i.e., the entorhinal, perirhinal, and parahippocampal cortices. One idea that has emerged from this work is that the severity of memory impairment might increase as more components of the medial temporal lobe are damaged. We have evaluated this idea directly by examining behavioral data from 30 monkeys (ten normal monkeys and 20 monkeys with bilateral lesions involving structures within the medial temporal lobe) that have completed testing on our standard memory battery during the last 10 years. The main finding was that the severity of memory impairment depended on the locus and extent of damage to the medial temporal lobe. Specifically, damage limited to the hippocampal region produced a mild memory impairment. More severe memory impairment was produced when the damage was increased to include the adjacent entorhinal and parahippocampal cortices (the H+ lesion). Finally, memory impairment was even more severe when the H+ lesion was extended forward to include the anterior entorhinal cortex and the perirhinal cortex (H++ lesion). Taken together, these findings suggest that, whereas damage to the hippocampal region produces measurable memory impairment, a substantial part of the severe memory impairment produced by large medial temporal lobe lesions in humans and monkeys can be attributed to damage to entorhinal, perirhinal, and parahippocampal cortices adjacent to the hippocampal region.