Andy C. H. Lee

Perceptual deficits in amnesia: challenging the medial temporal lobe 'mnemonic' view

Recent animal studies suggest that the medial temporal lobe (MTL), which is thought to subserve memory exclusively, may support non-mnemonic perceptual processes, with the hippocampus and perirhinal cortex contributing to spatial and object perception, respectively. There is, however, no support for this view in humans, with human MTL lesions causing prominent memory deficits in the context of apparently normal perception. We assessed visual discrimination in amnesic cases to reveal that while selective hippocampal damaged patients could discriminate faces, objects, abstract art and colour, they were significantly poorer in discriminating spatial scenes. By contrast, patients with MTL damage, including perirhinal cortex, were significantly impaired in discriminating scenes, faces, and to a lesser extent objects, with relatively intact discrimination of art and colour. These novel observations imply that the human MTL subserves both perceptual and mnemonic functions, with the hippocampus and perirhinal cortex playing distinct roles in spatial and object discrimination, respectively.

Going beyond LTM in the MTL: A synthesis of neuropsychological and neuroimaging findings on the role of the medial temporal lobe in memory and perception

Studies in rats and non-human primates suggest that medial temporal lobe (MTL) structures play a role in perceptual processing, with the hippocampus necessary for spatial discrimination, and the perirhinal cortex for object discrimination. Until recently, there was little convergent evidence for analogous functional specialisation in humans, or for a role of the MTL in processes beyond long-term memory. A recent series of novel human neuropsychological studies, however, in which paradigms from the animal literature were adapted and extended, have revealed findings remarkably similar to those seen in rats and monkeys. These experiments have demonstrated differential effects of distinct stimulus categories on performance in tasks for which there was no explicit requirement to remember information across trials. There is also accruing complementary evidence from functional neuroimaging that MTL structures show differential patterns of activation for scenes and objects, even on simple visual discrimination tasks. This article reviews some of these key studies and discusses the implications of these new findings for existing accounts of memory. A non-modular view of memory is proposed in which memory and perception depend upon the same anatomically distributed representations (emergent memory account). The limitations and criticisms of this theory are discussed and a number of outstanding questions proposed, including key predictions that can be tested by future studies.

Functional specialization in the human medial temporal lobe

Investigations of memory in rats and nonhuman primates have demonstrated functional specialization within the medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampal formation and underlying entorhinal, perirhinal, and parahippocampal cortices. Most studies in humans, however, especially in patients with brain damage, suggest that the human MTL is a unitary memory system supporting all types of declarative memory, our conscious memory for facts and events. To resolve this discrepancy, amnesic patients with either selective hippocampal damage or more extensive MTL damage were tested on variations of an object discrimination task adapted from the nonhuman primate literature. Although both groups were equally impaired on standard recall-based memory tasks, they exhibited different profiles of performance on the object discrimination test, arguing against a unitary view of MTL function. Cases with selective hippocampal damage performed normally, whereas individuals with broader MTL lesions were impaired. Furthermore, deficits in this latter group were related not to the number of discriminations to be learned and remembered, but to the degree of “feature ambiguity,” a property of visual discriminations that can emerge when features are part of both rewarded and unrewarded stimuli. These findings resolve contradictions between published studies in humans and animals and introduce a new way of characterizing the impairments that arise after damage to the MTL.

The neural basis of autobiographical and semantic memory: New evidence from three PET studies

A novel, neuropsychologically informed paradigm (extended retrieval of events in response to a cue word) was used to investigate the neural basis of autobiographical and semantic memory. Contrasting retrieval of autobiographical memories with retrieval of semantic facts (ABM — SEM) in 24 subjects across three PET studies revealed bilateral involvement of the middle temporal gyrus (BA 21) and medial frontal cortex (BA 9/10). The opposite contrast, SEM — ABM, resulted in increased regional cerebral blood flow in left posterior temporal regions (BA 37) and left prefrontal cortex (BA 45/46). Laterality maps suggest that the bilateral pattern seen in our studies, but not often in other neuroimaging investigations, reflects the use of a task stressing retrieval of specific personal events. Further comparisons revealed that the activation in the right anterior temporal lobe during autobiographical recall was virtually identical to that seen during retrieval of information about famous people or events in contrast with retrieval of general semantic facts. These findings suggest that the retrieval of an autobiographical event requires participation from conceptual knowledge, and that this type of knowledge is bilaterally distributed in the temporal lobes.

Differentiating the Roles of the Hippocampus and Perirhinal Cortex in Processes beyond Long-Term Declarative Memory: A Double Dissociation in Dementia

There is increasing evidence to suggest that the hippocampus and perirhinal cortex may mediate processes beyond long-term declarative memory. We assessed patients with Alzheimers disease (AD) or semantic dementia (SD) on a visual oddity judgment task that did not place an explicit demand on long-term memory and is known to be sensitive to hippocampal and perirhinal cortex lesions. Importantly, within the medial temporal lobe, AD is associated with predominant hippocampal atrophy, whereas SD patients have greater perirhinal cortex damage. The AD group was selectively impaired in oddity judgment for scenes, whereas the SD patients demonstrated a deficit in face oddity judgment only. This compelling double dissociation supports the idea that the hippocampus and perirhinal cortex may be critical for the processing of scenes and objects, respectively, in the domain of perception or very short-term working memory.

The hippocampus and visual perception

In this review, we will discuss the idea that the hippocampus may be involved in both memory and perception, contrary to theories that posit functional and neuroanatomical segregation of these processes. This suggestion is based on a number of recent neuropsychological and functional neuroimaging studies that have demonstrated that the hippocampus is involved in the visual discrimination of complex spatial scene stimuli. We argue that these findings cannot be explained by long-term memory or working memory processing or, in the case of patient findings, dysfunction beyond the medial temporal lobe (MTL). Instead, these studies point toward a role for the hippocampus in higher-order spatial perception. We suggest that the hippocampus processes complex conjunctions of spatial features, and that it may be more appropriate to consider the representations for which this structure is critical, rather than the cognitive processes that it mediates.

Medial temporal lobe activity during complex discrimination of faces, objects, and scenes: Effects of viewpoint

The medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampus and underlying entorhinal, perirhinal and parahippocampal cortex, is traditionally believed to be part of a unitary system dedicated to declarative memory. Recent studies, however, demonstrated perceptual impairments in amnesic individuals with MTL damage, with hippocampal lesions causing scene discrimination deficits, and perirhinal lesions causing object and face discrimination deficits. The degree of impairment on these tasks was influenced by the need to process complex conjunctions of features: discriminations requiring the integration of multiple visual features caused deficits, whereas discriminations that could be solved on the basis of a single feature did not. Here, we address these issues with functional neuroimaging in healthy participants as they performed a version of the oddity discrimination task used previously in patients. Three different types of stimuli (faces, scenes, novel objects) were presented from either identical or different viewpoints. Consistent with studies in patients, we observed increased perirhinal activity when participants distinguished between faces and objects presented from different, compared to identical, viewpoints. The posterior hippocampus, by contrast, showed an effect of viewpoint for both faces and scenes. These findings provide convergent evidence that the MTL is involved in processes beyond long‐term declarative memory and suggest a critical role for these structures in integrating complex features of faces, objects, and scenes into view‐invariant, abstract representations.

The contribution of the human medial temporal lobe to perception: bridging the gap between animal and human studies.

The medial temporal lobe (MTL) has been considered traditionally to subserve declarative memory processes only. Recent studies in nonhuman primates suggest, however, that the MTL may also be critical to higher order perceptual processes, with the hippocampus and perirhinal cortex being involved in scene and object perception, respectively. The current article reviews the human neuropsychological literature to determine whether there is any evidence to suggest that these same views may apply to the human MTL. Although the majority of existing studies report intact perception following MTL damage in human amnesics, there have been recent studies that suggest that when scene and object perception are assessed systematically, signifi-cant impairments in perception become apparent. These findings have important implications for current mnemonic theories of human MTL function and our understanding of human amnesia as a result of MTL lesions.

Associative and recognition memory for novel objects in dementia: implications for diagnosis.

It has been demonstrated that patients with dementia of the Alzheimers type show particular difficulties with a task that measures memory for object locations [R. Swainson et al. (2001) Dement. Geriatr. Cogn. Disord. 12, 265–80]. The present study followed on from this report by asking whether the deficits seen in dementia of the Alzheimers type were specific to this condition, or whether they would also be seen in another common neurodegenerative syndrome, frontotemporal dementia. To investigate this important issue, we examined memory for object–location pairs and visual recognition memory for novel patterns using two tests, the Paired Associates Learning and Matching to Sample tasks, from the Cambridge Neuropsychological Testing Automated Battery. The performance of a subset of the patients with dementia of the Alzheimers type described by Swainson et al., selected on the basis of age and education, was compared with matched groups of frontal variant frontotemporal dementia, semantic dementia and control subjects. In contrast to the patients with dementia of the Alzheimers type, who showed significant impairment on both memory tests, the two frontotemporal dementia groups did not perform significantly poorer compared with control subjects on nearly all memory measures, other than ‘memory score’ from the paired associates learning task. These findings confirm that tests of episodic memory, especially for the location of objects in space, may be useful in the early diagnosis and differentiation of dementia of the Alzheimers type.

Abnormal Categorization and Perceptual Learning in Patients with Hippocampal Damage

Prevailing theory holds that the medial temporal lobe (MTL) subserves declarative memory exclusively, whereas nondeclarative memory is independent of this brain region. Recent studies in patients with amnesia, however, have shown that performance on declarative memory tasks may not always be dependent on a single MTL memory system, instead highlighting the critical role of anatomically distinct structures in processing different stimulus types. In particular, the hippocampus has been implicated in spatial memory, whereas perirhinal cortex seems critical for object memory. To assess whether stimulus type would also be a key dimension in nondeclarative memory, patients with selective hippocampal lesions were tested on simple categorization and perceptual learning of faces and virtual reality scenes. The patients demonstrated preserved categorization and perceptual learning of faces but abnormal performance when the stimuli to be discriminated were virtual reality scenes. These findings imply that stimulus type may be a more critical predictor of performance on memory tasks (declarative and nondeclarative) than previously thought. They also suggest that reports of good nondeclarative memory after MTL damage may, in some cases, simply reflect the use of stimuli that fail to tap the processes dependent on structures in this region, such as spatial processing in the case of the hippocampus.