FDG-PET analysis and findings in amnesia resulting from hypoxia

The assumptions underlying neuroimaging, and problems in its analysis and interpretation, are commonly underestimated in neuropsychology. The ways in which fluoro-deoxy-glucose (FDG) positron emission tomography (PET) data can be analysed are discussed. PET findings from four patients who had suffered severe amnesia, following episodes of acute hypoxia, are presented. These patients had shown evidence of medial temporal (hippocampal and parahippocampal) atrophy on MRI brain scans. The PET data were analysed in several different ways. The converging findings were that the patients showed bilateral thalamic hypometabolism, and there was also evidence of retrosplenial hypometabolism bilaterally. Cognitively, these patients performed most like other patients with medial temporal lesions, but the results indicate that structural lesions can have distal metabolic effects on structures elsewhere. These findings are interpreted in the light of neuroanatomical observations concerning parallel projections between medial temporal lobe structures and the thalamus, some of which pass via the retrosplenium.     

Nonverbal Amnesia and Asymmetric Cerebral Lesions Following Encephalitis

Global amnesia after herpes simplex encephalitis has been typically associated with lesions of anterior and medial temporal lobe, inferior and medial frontal lobe, and insula. The neuropathologic correlates of this disease are usually considered to be bilateral and similar across cases. We describe a 27-year-old woman whose chronic amnesia and cerebral lesions after viral encephalitis indicate a different pattern. Two features distinguish her presentation: (1) markedly asymmetric lesions extensively involving the right temporal lobe but sparing almost all of the same structures on the left and (2) severe compromise of nonverbal learning and a nonverbal retrograde amnesia in contrast to disproportionately small impairments of verbal learning and retention. The findings suggest that encephalitis patients cannot be treated as a homogeneous group and that detailed analysis of variability in their anatomic lesions may be an important explanatory factor in neural accounts of these severe human amnesias.     

The role of the perirhinal cortex and hippocampus in learning, memory, and perception.

One traditional and long-held view of medial temporal lobe (MTL) function is that it contains a system of structures that are exclusively involved in memory, and that the extent of memory loss following MTL damage is simply related to the amount of MTL damage sustained. Indeed, human patients with extensive MTL damage are typically profoundly amnesic whereas patients with less extensive brain lesions centred upon the hippocampus typically exhibit only moderately severe anterograde amnesia. Accordingly, the latter observations have elevated the hippocampus to a particularly prominent position within the purported MTL memory system. This article reviews recent lesion studies in macaque monkeys in which the behavioural effects of more highly circumscribed lesions (than those observed to occur in human patients with MTL lesions) to different subregions of the MTL have been examined. These studies have reported new findings that contradict this concept of a MTL memory system. First, the MTL is not exclusively involved in mnemonic processes; some MTL structures, most notably the perirhinal cortex, also contribute to perception. Second, there are some forms of memory, including recognition memory, that are not always affected by selective hippocampal lesions. Third, the data support the idea that regional functional specializations exist within the MTL. For example, the macaque perirhinal cortex appears to be specialized for processing object identity whereas the hippocampus may be specialized for processing spatial and temporal relationships.     

逆行性遗忘、额叶与远期记忆的组织

通过对一例严重记忆障碍合并额叶损伤病人的逆行性遗忘的分析,对远期记忆的组织特点进行了探讨。被试的额叶功能受损较为明显。除顺行性遗忘外,患者的逆行性遗忘也较为严重。对病人进行的逆行性遗忘检测包括：著名人物测验、著名事件、一般知识测验和自传性记忆测验等。被试对著名人物、著名事件的回忆和再认成绩、以及有关个人的情节和语义记忆成绩均较低,但没有典型的随时间下降的趋势,而是呈平直斜率;患者儿童期的自传性记忆和公众事件记忆也受损。这两个特点均与内侧颞叶一间脑系统损伤的特点不同,提示额叶参与了远期记忆的提取等过程。     

The role of the perirhinal cortex and hippocampus in learning, memory, and perception

One traditional and long-held view of medial temporal lobe (MTL) function is that it contains a system of structures that are exclusively involved in memory, and that the extent of memory loss following MTL damage is simply related to the amount of MTL damage sustained. Indeed, human patients with extensive MTL damage are typically profoundly amnesic whereas patients with less extensive brain lesions centred upon the hippocampus typically exhibit only moderately severe anterograde amnesia. Accordingly, the latter observations have elevated the hippocampus to a particularly prominent position within the purported MTL memory system. This article reviews recent lesion studies in macaque monkeys in which the behavioural effects of more highly circumscribed lesions (than those observed to occur in human patients with MTL lesions) to different subregions of the MTL have been examined. These studies have reported new find-ings that contradict this concept of a MTL memory system. First, the MTL is not exclusively involved in mnemonic processes; some MTL structures, most notably the perirhinal cortex, also contribute to perception. Second, there are some forms of memory, including recognition memory, that are not always affected by selective hippocampal lesions. Third, the data support the idea that regional functional specializations exist within the MTL. For example, the macaque perirhinal cortex appears to be specialized for processing object identity whereas the hippocampus may be specialized for processing spatial and temporal relationships.     

Impaired auditory recognition memory in amnesic patients with medial temporal lobe lesions

Two tests of auditory recognition memory were given to four patients with bilateral hippocampal damage (H+) and three patients with large medial temporal lobe lesions and additional variable damage to lateral temporal cortex (MTL+). When single stimuli were presented, performance was normal across delays as long as 30 sec, presumably because information could be maintained in working memory through rehearsal. When lists of 10 stimuli were presented, performance was impaired after a 5-min delay. Patients with MTL+ lesions performed marginally worse than patients with H+ lesions, consistent with findings for recognition memory in other modalities. The findings show that auditory recognition, like recognition memory in other sensory modalities, is dependent on the medial temporal lobe.     

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.     

Dissociation between the effects of damage to perirhinal cortex and area TE

Perirhinal cortex and area TE are immediately adjacent to each other in the temporal lobe and reciprocally interconnected. These areas are thought to lie at the interface between visual perception and visual memory, but it has been unclear what their separate contributions might be. In three experiments, monkeys with bilateral lesions of the perirhinal cortex exhibited a different pattern of impairment than monkeys with bilateral lesions of area TE. In experiment 1, lesions of the perirhinal cortex produced a multimodal deficit in recognition memory (delayed nonmatching to sample), whereas lesions of area TE impaired performance only in the visual modality. In experiment 2, on a test of visual recognition memory (the visual paired comparison task) lesions of the perirhinal cortex impaired performance at long delays but spared performance at a very short delay. In contrast, lesions of area TE impaired performance even at the short delay. In experiment 3, lesions of the perirhinal cortex and lesions of area TE produced an opposite pattern of impairment on two visual discrimination tasks, simple object discrimination learning (impaired only by perirhinal lesions), and concurrent discrimination learning (impaired only by TE lesions). Taken together, the findings suggest that the perirhinal cortex, like other medial temporal lobe structures, is important for the formation of memory, whereas area TE is important for visual perceptual processing.     

Perirhinal cortex lesions produce retrograde amnesia for spatial information in rats: consolidation or retrieval?

Several lines of evidence in humans and experimental animals suggest that the hippocampus is critical for the formation and retrieval of spatial memory. However, although the hippocampus is reciprocally connected to adjacent cortices within the medial temporal lobe and they, in turn, are connected to the neocortex, little is known regarding the function of these cortices in memory. Here, using a reference spatial memory task in the radial maze, we show that neurotoxic perirhinal cortex lesions produce a profound retrograde amnesia when learning-surgery intervals of 1 or 50 d are used (Experiment 1). With the aim of dissociating between consolidation and retrieval processes, we injected lidocaine either daily after training (Experiment 2) or before a retention test once the learning had been completed (Experiment 3). Results show that reversible perirhinal inactivation impairs retrieval but not consolidation. However, the same procedure followed in Experiment 2 disrupted consolidation when the lidocaine was injected into the dorsal hippocampus. The results of Experiment 4 rule out the possibility that the deficit in retrieval is due to a state-dependent effect. These findings demonstrate the differential contribution of various regions of the medial temporal lobe to memory, suggesting that the perirhinal cortex plays a key role in the retrieval of spatial information for a long period of time.     

内侧颞叶与来源记忆

来源记忆不同于项目记忆。早期的研究认为来源记忆的神经基础主要是前额叶,但近几年的相关研究发现内侧颞叶在来源记忆中的作用也是相当重要的,健康被试的功能神经成像研究和内侧颞叶损伤病人研究都为内侧颞叶在来源记忆中的作用提供了可靠证据。     

Impairment in material-specific long-term memory following unilateral mediodorsal thalamic damage and presumed partial disconnection of the mammillo-thalamic tract

Neuropsychological findings suggest material-specific lateralization of the medial temporal lobe's role in long-term memory, with greater left-sided involvement in verbal memory, and greater right-sided involvement in visual memory. Whether material-specific lateralization of long-term memory also extends to the anteromedial thalamus remains uncertain. We report two patients with unilateral right (OG) and left (SM) mediodorsal thalamic pathology plus probable correspondingly lateralized damage of the mammillo-thalamic tract. The lesions were mapped using high-resolution structural magnetic resonance imaging and schematically reconstructed. Mean absolute volume estimates for the mammillary bodies, hippocampus, perirhinal cortex, and ventricles are also presented. Estimates of visual and verbal recall and item recognition memory were obtained using the Doors and People, the Rey Complex Figure Test, and the Logical Memory subtests of the Wechsler Memory Scales. Each patient's performance was compared to a group of healthy volunteers matched for demographic characteristics, premorbid IQ, and current levels of functioning. A striking double dissociation was evident in material-specific long-term memory, with OG showing significant impairments in visual memory but not verbal memory, and SM showing the opposite profile of preserved visual memory and significantly impaired verbal memory. These impairments affected both recall and item recognition. The reported double dissociation provides the strongest evidence yet that material-specific lateralization of long-term memory also extends to the anteromedial thalamus. The findings are also discussed in relation to proposals that distinct anatomical regions within the medial temporal lobe, anteromedial thalamus, and associated tracts make qualitatively different contributions to recall and item recognition.     

Memory for frequency in rats: role of the hippocampus and medial prefrontal cortex

On a radial arm maze rats were tested for frequency memory of specific spatial locations, a task that presumably involves the coding of temporal information. On any trial during the study phase rats were allowed to visit three different spatial locations only once and one spatial location twice. During the test phase the rats were given a choice between a spatial location that had been visited once and spatial location that had been visited twice. The rats were reinforced for selecting the twice-visited spatial location. The number of spatial locations between a repetition (lag) was varied from one to three. After extensive training rats displayed memory for frequency only for a lag of three spatial locations, i.e., they displayed a repetition lag effect. Animals then received control, medial prefrontal cortex, or hippocampal lesions. Upon subsequent retests control rats continued to display frequency memory, but animals with medial prefrontal cortex or hippocampal lesions displayed a marked impairment. These data support the idea that both the hippocampus and medial prefrontal cortex code temporal order information.     

The neuroimaging of long-term memory encoding processes

There needs to be more crosstalk between the lesion and functional neuroimaging memory literatures. This is illustrated by a discussion of episode and fact encoding. The lesion literature suggests several hypotheses about which brain regions underlie the storage of episode and fact information, which can be explored by functional neuroimaging. These hypotheses have been underexplored because neuroimaging studies of encoding have been insufficiently hypothesis-driven and have not controlled encoding-related processes sufficiently well to allow clear interpretations of results to be made. Nevertheless, there is good evidence that certain kinds of associative encoding and/or consolidation are sufficient to activate the medial temporal lobes, and preliminary evidence that some kinds of associative priming may reduce activation of this region. It remains to be proved that attentional orienting to certain kinds of novel information activates the medial temporal lobes. Evidence is growing that the HERA model, developed from neuroimaging rather than lesion data, requires modification and that frontal cortex encoding activations are probably caused by executive processes that are important in effortful memory processing. Neuroimaging studies allow the detection of encoding-related activations in previously unexpected brain regions (e.g. parietal lobes) and, in turn, these findings can be explored with lesion studies.     

The Neuroimaging of Long-term Memory Encoding Processes

There needs to be more crosstalk between the lesion and functional neuroimaging memory literatures. This is illustrated by a discussion of episode and fact encoding. The lesion literature suggests several hypotheses about which brain regions underlie the storage of episode and fact information, which can be explored by functional neuroimaging. These hypotheses have been underexplored because neuroimaging studies of encoding have been insufficiently hypothesis-driven and have not controlled encoding-related processes sufficiently well to allow clear interpretations of results to be made. Nevertheless, there is good evidence that certain kinds of associative encoding and/or consolidation are sufficient to activate the medial temporal lobes, and preliminary evidence that some kinds of associative priming may reduce activation of this region. It remains to be proved that attentional orienting to certain kinds of novel information activates the medial temporal lobes. Evidence is growing that the HERA model, developed from neuroimaging rather than lesion data, requires modification and that frontal cortex encoding activations are probably caused by executive processes that are important in effortful memory processing. Neuroimaging studies allow the detection of encoding-related activations in previously unexpected brain regions (e.g. parietal lobes) and, in turn, these findings can be explored with lesion studies.     

The anatomy of amnesia: neurohistological analysis of three new cases

The most useful information about the anatomy of human memory comes from cases where there has been extensive neuropsychological testing followed by detailed post-mortem neurohistological analysis. To our knowledge, only eight such cases have been reported (four with medial temporal lobe damage and four with diencephalic damage). Here we present neuropsychological and post-mortem neurohistological findings for one patient (NC) with bilateral damage to the medial temporal lobe and two patients (MG, PN) with diencephalic damage due to bilateral thalamic infarction and Korsakoff's syndrome, respectively. All three patients exhibited a similar phenotype of amnesia with markedly impaired declarative memory (anterograde and retrograde) but normal performance on tests of nondeclarative memory (e.g., priming and adaptation-level effects) as well as on tests of other cognitive functions. Patient NC had damage to the hippocampus (dentate gyrus and the CA1 and CA3 fields) and layer III of the entorhinal cortex, but with relative sparing of the CA2 field and the subiculum. Patient MG had damage to the internal medullary lamina and mediodorsal thalamic nuclei. Patient PN had damage to the mammillary nuclei, mammillothalamic tracts, and the anterior thalamic nuclei. These findings illuminate several issues regarding the relation between diencephalic and medial temporal lobe amnesia, the status of recognition memory in amnesia, and the neuroanatomy of memory.     

Auditory/visual duration bisection in patients with left or right medial-temporal lobe resection

Patients with unilateral (left or right) medial temporal lobe lesions and normal control (NC) volunteers participated in two experiments, both using a duration bisection procedure. Experiment 1 assessed discrimination of auditory and visual signal durations ranging from 2 to 8 s, in the same test session. Patients and NC participants judged auditory signals as longer than equivalent duration visual signals. The difference between auditory and visual time discrimination was equivalent for the three groups, suggesting that a unilateral temporal lobe resection does not modulate the modality effect. To document interval-timing abilities after temporal lobe resection for different duration ranges, Experiment 2 investigated the discrimination of brief, 50-200 ms, auditory durations in the same patients. Overall, patients with right temporal lobe resection were found to have more variable duration judgments across both signal modality and duration range. These findings suggest the involvement of the right temporal lobe at the level of the decision process in temporal discriminations.     

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

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.     

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, significant 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.     

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.     

Learning related modulation of functional retrieval networks in man

The medial temporal lobe has been implicated in studies of episodic memory tasks involving spatio-temporal context and object-location conjunctions. We have previously demonstrated that an increased level of practice in a free-recall task parallels a decrease in the functional activity of several brain regions, including the medial temporal lobe, the prefrontal, the anterior cingulate, the anterior insular, and the posterior parietal cortices, that in concert demonstrate a move from elaborate controlled processing towards a higher degree of automaticity. Here we report data from two experiments that extend these initial observations. We used a similar experimental approach but probed for effects of retrieval paradigms and stimulus material. In the first experiment we investigated practice related changes during recognition of object-location conjunctions and in the second during free-recall of pseudo-words. Learning in a neural network is a dynamic consequence of information processing and network plasticity. The present and previous PET results indicate that practice can induce a learning related functional restructuring of information processing. Different adaptive processes likely subserve the functional re-organisation observed. These may in part be related to different demands for attentional and working memory processing. It appears that the role(s) of the prefrontal cortex and the medial temporal lobe in memory retrieval are complex, perhaps reflecting several different interacting processes or cognitive components. We suggest that an integrative interactive perspective on the role of the prefrontal and medial temporal lobe is necessary for an understanding of the processing significance of these regions in learning and memory. It appears necessary to develop elaborated and explicit computational models for prefrontal and medial temporal functions in order to derive detailed empirical predictions, and in combination with an efficient use and development of functional neuroimaging approaches, to further the understanding of the processing significance of these regions in memory.