Medial Temporal Lobe Amnesia Research Articles

Evidence of Impaired Remote Experience-near Semantic Memory in Medial Temporal Lobe Amnesia.

Neuropsychological research suggests that "experience-near" semantic memory, meaning knowledge attached to a spatiotemporal or event context, is commonly impaired in individuals who have medial temporal lobe amnesia. It is not known if this impairment extends to remotely acquired experience-near knowledge, which is a question relevant to understanding hippocampal/medial temporal lobe functioning. In the present study, we administered a novel semantic memory task designed to target knowledge associated with remote, "dormant" concepts, in addition to knowledge associated with active concepts, to four individuals with medial temporal lobe amnesia and eight matched controls. We found that the individuals with medial temporal lobe amnesia generated significantly fewer experience-near semantic memories for both remote concepts and active concepts. In comparison, the generation of abstract or "experience-far" knowledge was largely spared in the individuals with medial temporal lobe amnesia, regardless of whether the targets for retrieval were remote or active concepts. We interpret these findings as evidence that the medial temporal lobes may have a sustained role in the retrieval of semantic memories associated with spatiotemporal and event contexts, which are cognitive features often ascribed to episodic memory. These results align with recent theoretical models proposing that the hippocampus/medial temporal lobes support cognitive processes that are involved in, but not exclusive to, episodic memory.

Altered learning and transfer abilities in Korsakoff’s syndrome depending on task complexity

Korsakoff’s syndrome (KS) is characterized by episodic memory impairment due to damage to the medial diencephalic structures. Although commonly associated with chronic alcoholism, starvation due to the hunger strike is one of its nonalcoholic causes. Learning the stimulus-response associations and transferring the just-learned associations to novel combinations were previously tested by specific tasks in memory-impaired patients with hippocampal, basal forebrain, and basal ganglia damage. To add to this previous research, we aimed to use the same tasks in a group of patients with hunger strike-related KS presenting a stable isolated amnestic profile. Twelve patients with hunger strike-related KS and matched healthy controls were tested in two tasks varying in task complexity. Each task included two phases: the initial phase is feedback-based learning of (simple vs. complex) stimulus-response associations, and the following phase is transfer generalization (in the presence vs. absence of feedback). On a task involving simple associations, five patients with KS failed to learn the associations, while the other seven patients showed intact learning and transfer. On the other task involving more complex associations, seven patients showed slower learning and failed at transfer generalization, whereas the other five patients failed even at the acquisition phase. These findings of a task-complexity-related impairment on associative learning and transfer represent a distinct pattern from the spared learning but impaired transfer previously observed on these tasks in patients with medial temporal lobe amnesia.

The status of semantic memory in medial temporal lobe amnesia varies with demands on scene construction

Semantic memory is typically preserved in medial temporal lobe (MTL) amnesia. However, there are instances of impairment, such as in the recall of semantic narratives. As some forms of semantic knowledge play out in a spatial context, one possible explanation is that semantic memory impairments, when observed, relate to demands on scene construction – the ability to bind and maintain spatial information in a coherent representation. To investigate whether semantic memory impairments in MTL amnesia can be understood with reference to a deficit in scene construction, the current study examined knowledge of scripts that vary in the extent to which they play out in a scene context in nine patients with MTL amnesia and eighteen healthy control subjects. Scripts are routine activities characterized by an ordered set of actions, including some that are essential for completing the activity. Comparing performance on scene-based scripts (e.g., buying groceries at the grocery store) and object-based scripts (e.g., addressing a letter), we found that patients generated the same number of total action steps as controls for both types of script, but patients were selectively impaired at generating essential actions steps for scene-based scripts. Furthermore, patients made more sequencing and idiosyncratic errors than controls in the scene-based, but not in the object-based, scripts. These findings demonstrate that the hippocampus plays a critical role in the retrieval of semantic knowledge about everyday activities when such retrieval entails scene construction.

Relational processing in the semantic domain is impaired in medial temporal lobe amnesia

It has been argued that the hippocampus supports cognition by virtue of its role in flexibly binding together distinct elements of experience. Such 'relational processing' enables us to (re)construct episodic representations of real or imagined events. The present study examined whether hippocampally mediated relational processing also contributes to the construction of semantic representations. To do so, we asked amnesic individuals with medial temporal lobe (MTL) lesions including the hippocampus to generate hypothetical meanings for novel word compounds (e.g., cactus carpet), a task that requires existing concepts to be flexibly linked. The quality of definitions and number of features generated for the novel compounds were lower in patients with MTL lesions than in control participants. Whereas the subset of patients with lesions extending into lateral temporal cortex had additional difficulty generating meanings for pre-existing compounds (e.g., bus station), patients with lesions limited to the MTL showed no such deficit, indicating that their impairment in the novel compound condition was not due to reduced access to semantic information. These findings suggest that the role of hippocampally mediated relational processing extends beyond the episodic domain to include the generation of novel semantic representations.

Medial Temporal Lobe Amnesia Is Associated with a Deficit in Recovering Temporal Context.

Medial-temporal lobe (MTL) lesions are associated with severe impairments in episodic memory. In the framework of the temporal context model, the hypothesized mechanism for episodic memory is the reinstatement of a prior experienced context (i.e., "jump back in time"), which relies upon the MTL [Howard, M. W., Fotedar, M. S., Datey, A. V., & Hasselmo, M. E. The temporal context model in spatial navigation and relational learning: Toward a common explanation of medial temporal lobe function across domains. Psychological Review, 112, 75-116, 2005]. This hypothesis has proven difficult to test in amnesia because of the floor-level performance by patients in recall tasks. To circumvent this issue, in this study, we used a "looped-list" format, in which a set of verbal stimuli was presented multiple times in a consistent order. This allowed for comparison of statistical properties such as probability of first recall and lag-conditional response probability (lag-CRP) between amnesic patients and healthy controls. Results revealed that the lag-CRP, but not the probability of first recall, is altered in amnesia, suggesting a selective disruption of temporal contiguity. To further characterize the results, we fit a scale-invariant version of the temporal context model [Howard, M. W., Shankar, K. H., Aue, W. R., & Criss, A. H. A distributed representation of internal time. Psychological Review, 122, 24-53, 2015] to the probability of first recall and lag-CRP curves. The modeling results suggested that the deficit in temporal contiguity in amnesia is best described as a failure to recover temporal context. These results provide the first direct evidence for an impairment in a jump-back-in-time mechanism in patients with MTL amnesia.

Impaired Recent, but Preserved Remote, Autobiographical Memory in Pediatric Brain Tumor Patients.

Medulloblastomas, the most common malignant brain tumor in children, are typically treated with radiotherapy. Refinement of this treatment has greatly improved survival rates in this patient population. However, radiotherapy also profoundly affects the developing brain and is associated with reduced hippocampal volume and blunted hippocampal neurogenesis. Such hippocampal (as well as extrahippocampal) abnormalities likely contribute to cognitive impairments in this population. While several aspects of memory have been examined in this population, the impact of radiotherapy on autobiographical memory has not previously been evaluated. Here we evaluated autobiographical memory in male and female patients who received radiotherapy for posterior fossa tumors (PFTs), including medulloblastoma, during childhood. Using the Children's Autobiographical Interview, we retrospectively assessed episodic and nonepisodic details for events that either preceded (i.e., remote) or followed (i.e., recent) treatment. For post-treatment events, PFT patients reported fewer episodic details compared with control subjects. For pretreatment events, PFT patients reported equivalent episodic details compared with control subjects. In a range of conditions associated with reduced hippocampal volume (including medial temporal lobe amnesia, mild cognitive impairment, Alzheimer's disease, temporal lobe epilepsy, transient epileptic amnesia, frontal temporal dementia, traumatic brain injury, encephalitis, and aging), loss of episodic details (even in remote memories) accompanies hippocampal volume loss. It is therefore surprising that pretreatment episodic memories in PFT patients with reduced hippocampal volume are retained. We discuss these findings in light of the anterograde and retrograde impact on memory of experimentally suppressing hippocampal neurogenesis in rodents.SIGNIFICANCE STATEMENT Pediatric medulloblastoma survivors develop cognitive dysfunction following cranial radiotherapy treatment. We report that radiotherapy treatment impairs the ability to form new autobiographical memories, but spares preoperatively acquired autobiographical memories. Reductions in hippocampal volume and cortical volume in regions of the recollection network appear to contribute to this pattern of preserved preoperative, but impaired postoperative, memory. These findings have significant implications for understanding disrupted mnemonic processing in the medial temporal lobe memory system and in the broader recollection network, which are inadvertently affected by standard treatment methods for medulloblastoma tumors in children.

A Computational Model of Perceptual and Mnemonic Deficits in Medial Temporal Lobe Amnesia.

Damage to the medial temporal lobe (MTL) has long been known to impair declarative memory, and recent evidence suggests that it also impairs visual perception. A theory termed the representational-hierarchical account explains such impairments by assuming that MTL stores conjunctive representations of items and events, and that individuals with MTL damage must rely upon representations of simple visual features in posterior visual cortex, which are inadequate to support memory and perception under certain circumstances. One recent study of visual discrimination behavior revealed a surprising antiperceptual learning effect in MTL-damaged individuals: With exposure to a set of visual stimuli, discrimination performance worsened rather than improved [Barense, M. D., Groen, I. I. A., Lee, A. C. H., Yeung, L. K., Brady, S. M., Gregori, M., et al. Intact memory for irrelevant information impairs perception in amnesia. Neuron, 75, 157-167, 2012]. We extend the representational-hierarchical account to explain this paradox by assuming that difficult visual discriminations are performed by comparing the relative "representational tunedness"-or familiarity-of the to-be-discriminated items. Exposure to a set of highly similar stimuli entails repeated presentation of simple visual features, eventually rendering all feature representations maximally and, thus, equally familiar; hence, they are inutile for solving the task. Discrimination performance in patients with MTL lesions is therefore impaired by stimulus exposure. Because the unique conjunctions represented in MTL do not occur repeatedly, healthy individuals are shielded from this perceptual interference. We simulate this mechanism with a neural network previously used to explain recognition memory, thereby providing a model that accounts for both mnemonic and perceptual deficits caused by MTL damage with a unified architecture and mechanism.

A new method for assessing the impact of medial temporal lobe amnesia on the characteristics of generated autobiographical events

Constructing autobiographical events involves an initial phase of event selection, in which a memory or imagined future event is initially brought to mind, followed by a phase of elaboration, in which an individual accesses detailed knowledge specific to the event. While considerable research demonstrates the importance of the medial temporal lobes (MTL) in the later phase, its role in initial event selection is unknown. The present study is the first to investigate the role of the MTL in event selection by assessing whether individuals with MTL lesions select qualitatively different events for remembering and imagining than matched control participants. To do so, we created “event captions” that reflected the type of events selected for an autobiographical event narrative task by four individuals with MTL amnesia and control counterparts. Over 450 online raters assessed these event captions on qualitative dimensions known to vary with autobiographical recall (frequency, significance, emotionality, imageability, and uniqueness). Our critical finding was that individuals with MTL amnesia were more prone to select events that were rated as more frequently occurring than healthy control participants. We interpret this finding as evidence that people with impaired episodic memory from MTL damage compensate for their compromised ability to recall detailed information by relying more heavily on semantic memory processes to select generalized events. We discuss the implications for theoretical models of memory and methodological approaches to studying autobiographical memory.

Experience-near but not experience-far autobiographical facts depend on the medial temporal lobe for retrieval: Evidence from amnesia

This paper addresses the idea that there may be two types of autobiographical facts with distinct cognitive and neural mechanisms: “Experience-near” autobiographical facts, which contain spatiotemporal content derived from personal experience and thus depend on the medial temporal lobe (MTL) for retrieval, and “experience-far” autobiographical facts, which are abstract memories and thus rely on neocortical brain regions involved in retrieval of general semantic memory. To investigate this conceptual model of autobiographical fact knowledge, we analyzed the nature of autobiographical facts that were generated by 8 individuals with MTL amnesia and 12 control participants in a recent study of identity and memory [Grilli, M.D., & Verfaellie, M. (2015). Supporting the self-concept with memory: insight from amnesia. Social Cognitive and Affective Neuroscience, 10, 1684–1692]. Results revealed that MTL amnesic participants generated fewer experience-near autobiographical facts than controls. Experience-far autobiographical fact generation was not impaired in amnesic participants with damage restricted to the MTL, but there was preliminary evidence to suggest that it may be impaired in amnesic participants with damage to the MTL and anterior lateral temporal lobe. These results support a cognitive and neural distinction between experience-near and experience-far autobiographical facts and have implications for understanding the contribution of autobiographical fact knowledge to self-related cognition.

Specific, personally meaningful cues can benefit episodic prospection in medial temporal lobe amnesia.

To determine whether severity of episodic prospection impairment in medial temporal lobe (MTL) amnesia is reduced by the types of cues that are used to elicit personal future episodes and, if so, whether episodic memory impairment is similarly affected. Multiple case study of five individuals with MTL amnesia and healthy control participants. Participants were administered two tests of episodic prospection: A commonly used Galton-Crovitz task that uses generic cues (e.g., lemon) and a novel task that includes specific, personally meaningful cues referring to planned or plausible future events (e.g., granddaughter's recital). Narratives were scored for episodic detail using the Autobiographical Interview protocol (Levine etal., 2002), which distinguishes between internal (episodic) details and external (non-episodic) details. Results showed that specific, personally meaningful cues led to an appreciable reduction of episodic memory and prospection impairment in three of the amnesic cases tested. Clinical benefit from more structured, self-related cues may depend on factors such as extent of MTL damage or general severity of episodic memory and prospection impairment, highlighting the importance of methodological approaches to neuropsychological research that treat each case on an individual basis. In cases of mild-moderate amnesia, specific, personal cues afford more detailed episodic remembering and prospective imagining than individual cue words. Previous reports of episodic prospection impairment in medial temporal lobe (MTL) amnesia might misrepresent an individual case's true prospective abilities Specific cues drawn from a patient's everyday life have greater ecological validity than the more typical generic cues used to elicit episodic prospection and can aid some individuals with MTL amnesia in the ability to imagine future experiences Assessment and rehabilitation tools for MTL amnesic populations should attempt to minimize broad, open-ended questions and instead provide more structured and personally meaningful cues to guide responses Further research is needed to determine case-specific characteristics that best predict benefit from specific, personal cues. These might include extent of MTL damage and overall severity of episodic memory and prospection impairment.

A retroactive spatial cue improved VSTM capacity in mild cognitive impairment and medial temporal lobe amnesia but not in healthy older adults

Visual short-term memory (VSTM) is a vital cognitive ability, connecting visual input with conscious awareness. VSTM performance declines with mild cognitive impairment (MCI) and medial temporal lobe (MTL) amnesia. Many studies have shown that providing a spatial retrospective cue (“retrocue”) improves VSTM capacity estimates for healthy young adults. However, one study has demonstrated that older adults are unable to use a retrocue to inhibit irrelevant items from memory. It is unknown whether patients with MCI and MTL amnesia will be able to use a retrocue to benefit their memory. We administered a retrocue and a baseline (simultaneous cue, “simucue”) task to young adults, older adults, MCI patients, and MTL cases. Consistent with previous findings, young adults showed a retrocue benefit, whereas healthy older adults did not. In contrast, both MCI patients and MTL cases showed a retrocue benefit – the use of a retrocue brought patient performance up to the level of age-matched controls. We speculate that the patients were able to use the spatial information from the retrocue to reduce interference and facilitate binding items to their locations.

Supporting the self-concept with memory: insight from amnesia.

We investigated the extent to which personal semantic memory supports the self-concept in individuals with medial temporal lobe amnesia and healthy adults. Participants completed eight 'I Am' self-statements. For each of the four highest ranked self-statements, participants completed an open-ended narrative task, during which they provided supporting information indicating why the I Am statement was considered self-descriptive. Participants then completed an episodic probe task, during which they attempted to retrieve six episodic memories for each of these self-statements. Supporting information was scored as episodic, personal semantic or general semantic. In the narrative task, personal semantic memory predominated as self-supporting information in both groups. The amnesic participants generated fewer personal semantic memories than controls to support their self-statements, a deficit that was more pronounced for trait relative to role self-statements. In the episodic probe task, the controls primarily generated unique event memories, but the amnesic participants did not. These findings demonstrate that personal semantic memory, in particular autobiographical fact knowledge, plays a critical role in supporting the self-concept, regardless of the accessibility of episodic memories, and they highlight potential differences in the way traits and roles are supported by personal memory.

Medial temporal lobe amnesia impairs performance on a free association task

A growing body of evidence suggests that the hippocampus contributes to performance (or is implicated) in non-memory domains from perception to problem solving. In a previous study we found that hippocampal contribution to exemplar generation in a fluency task was determined jointly by the open-endedness of the task and its ability to elicit episodic memories (Sheldon and Moscovitch (2012) Hippocampus 22:1451-1466). In the current study, we extend these observations by exploring the role of the hippocampus in generative, goal-directed open-ended thought in patients with medial temporal lobe (MTL) amnesia on a free association task (think of words as they come to mind). Patients and control participants were asked to associate freely for one minute to cue words that varied in the open-endedness of the responses they elicited (greater for low- than high-frequency words), and in the ease with which episodic memories were evoked (greater for high imageable than low imageable words). As predicted, MTL amnesia patients generated fewer words than control participants when cues were highly imageable and low in frequency, but performed equivalently to them in the other conditions. These results support our prediction that the hippocampus contributes to free association, and possibly more generally to other generative tasks that are open-ended, creative, or that elicit the use of contextual and likely episodic memories in order to derive relevant information.

Susceptibility to interference and intrusion errors in consequence of the dominant hemisphere’s hippocampal infarct: A case report

We present a case of a man with an ischemic lesion of the left hippocampus. Detailed neuropsychological assessment revealed susceptibility to retroactive interference and a tendency to make intrusion errors in addition to mild deficits in the verbal memory processes. Although retroactive interference and intrusion errors are normally considered to be the manifestations of frontal lobe dysfunctions, the idea of susceptibility to interference has recently begun to emerge in the literature, as an explanation of medial temporal lobe amnesia. Our data support this new theory, suggesting that one role of the hippocampus is to decrease the interference during the learning processes.

It's All Coming Back to Me Now: Perception and Memory in Amnesia

Medial temporal lobe (MTL) structures may constitute a representational hierarchy, rather than a dedicated system for memory. Barense et al. (2012) show that intact memory for object features can interfere with perception of complex objects in individuals with MTL amnesia.

Associative working memory and subsequent episodic memory in Alzheimer’s disease

Recent studies indicate deficits in associative working memory in patients with medial-temporal lobe amnesia. However, it is unclear whether these deficits reflect working memory processing or are due to hippocampally mediated long-term memory impairment. We investigated associative working memory in relation to subsequent episodic memory formation in patients with early Alzheimer's disease to examine whether these findings reflect deficits in long-term encoding rather than 'pure' working memory processing. Nineteen patients with Alzheimer's disease and 21 controls performed a working memory task in which objects had to be searched at different locations. The subsequent episodic memory test required participants to reposition objects to their original locations. Patients with Alzheimer's disease were impaired on associative working memory and subsequent episodic memory, but they performed above chance at high-load episodic memory trials. This suggests that when working memory capacity is exceeded, long-term memory compensates.

The amnesias.

Throughout history, memory and amnesia have been central to philosophical thought and empirical investigation. There has been particular interest in whether there are multiple forms of memory, how they are represented in the brain, how they are parsed following neurological compromise, and how their breakdown is best characterized. Differential abilities among amnestic individuals have advanced the distinction between various forms of memory, such as implicit and explicit memory in the case of H.M., and episodic and semantic memory in the case of K.C. This overview brings together a variety of perspectives on memory and the amnesias, from Clinical Neuropsychology, Neurology, and Cognitive Science, to Animal and Human Neuroscience. We begin with a brief history of the study of memory organization in the healthy brain and dissociations in memory as uncovered in extensively studied cases of amnesia. Memory impairment resulting from damage to the medial temporal lobe (MTL), diencephalon, basal forebrain, and the frontal lobes is then elaborated, with a focus on MTL amnesia, which has received the most attention among memory researchers. Alternative theories of MTL amnesia are considered through a selective review of the current amnesia and neuroimaging literatures on the seemingly disparate roles of the hippocampus in episodic and spatial memory, future imagining, perception, implicit memory, and working memory. If amnesia is a disorder that is not restricted to explicit (consciously accessible) memory, this will force us to rethink the way in which memory is represented in the human brain. WIREs Cogn Sci 2012, 3:47-63. doi: 10.1002/wcs.155 For further resources related to this article, please visit the WIREs website.

Intact Performance on Feature-Ambiguous Discriminations in Rats with Lesions of the Perirhinal Cortex

We developed a behavioral paradigm for the rat that made it possible to separate the evaluation of memory functions from the evaluation of perceptual functions. Animals were given extensive training on an automated two-choice discrimination task and then maintained their memory performance at a high level while interpolated probe trials tested visual perceptual ability. The probe trials systematically varied the degree of feature ambiguity between the stimuli, such that perceptual functions could be tested across 14 different levels of difficulty. As feature ambiguity increased, performance declined in an orderly, monotonic manner (from 87% correct to chance, 50% correct). Bilateral lesions of the perirhinal cortex fully spared the capacity to make feature-ambiguous discriminations and the performance of lesioned and intact animals was indistinguishable at every difficulty level. In contrast, the perirhinal lesions did impair recognition memory. The findings suggest that the perirhinal cortex is important for memory and not for perceptual functions.

Figure-ground perception is impaired in medial temporal lobe amnesia

Figure-ground perception is impaired in medial temporal lobe amnesia

Hippocampus and retrograde amnesia in the rat model: A modest proposal for the situation of systems consolidation

The properties of retrograde amnesia after damage to the hippocampus have been explicated with some success using a rat model of human medial temporal lobe amnesia. We review the results of this experimental work with rats focusing on several areas of consensus in this growing literature. We evaluate the theoretically significant hypothesis that hippocampal retrograde amnesia normally exhibits a temporal gradient, affecting recent, but sparing remote memories. Surprisingly, the evidence does not provide much support for the idea that there is a lengthy process of systems consolidation following a learning episode. Instead, recent and remote memories tend to be equally affected. The extent of damage to the hippocampus is a significant factor in this work since it is likely that spared hippocampal tissue can support at least partial memory retrieval. With extensive hippocampal damage gradients are flat or, in the case of memory tasks with flavour/odour retrieval cues, the retrograde amnesia covers a period of about 1–3 days. There is consistent evidence that at the time of learning the hippocampus interferes with or overshadows memory acquisition by other systems. This contributes to the breadth and severity of retrograde amnesia relative to anterograde amnesia in the rat. The fact that multiple, distributed learning episodes can overcome this overshadowing is consistent with a parallel dual-store theory or a Distributed Reinstatement Theory in which each learning episode triggers a short period of memory replay that provides a brief hippocampal-dependent systems consolidation.