Amnesic Individuals Research Articles

The hippocampus supports precise memory for public events regardless of their remoteness

The necessity of the human hippocampus and surrounding medial temporal lobe structures to semantic memory remains contentious. Impaired semantic memory following hippocampal lesions could arise either due to partially intertwined episodic memories and/or retrograde/anterograde effects. In this study, we tested amnesic individuals with lesions in hippocampus and surrounding medial temporal lobe (n = 7) and age-matched controls (n = 14) on their ability to precisely recall the dates of famous public events that occurred either before (i.e., pre-lifetime) or after participants’ birth date (lifetime). We show that deficits in dating precision are greatest for recent lifetime events, consistent with the notion that recent event memory may be particularly intertwined with episodic memory. At the same time, individuals with medial temporal lobe lesions showed more subtle impairments in their ability to date pre-birth and remote lifetime events precisely. Together, these findings suggest that the hippocampus and surrounding medial temporal lobe structures are important for representational precision of semantic memories regardless of their remoteness.

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.

Re-learning and remembering in the lesioned brain

It is well known that re-learning language skills after a brain lesion can be very difficult. However, while learning and memory challenges have been extensively researched in amnesic individuals, very little research attention has been directed at understanding the characteristics of learning and memory that are relevant to recovery and rehabilitation of acquired language impairments. Even in the absence of damage to the medial temporal lobe regions classically associated with learning and memory, these individuals often suffer damage to frontal and other subcortical areas associated with learning and memory that may contribute to the learning challenges they face. Therefore, an understanding of the learning and memory profiles of post-stroke language impairments is important for the development and optimization of rehabilitation approaches. In two studies, we examine the degree to which certain basic characteristics of learning and memory, identified in neurotypical individuals, are intact in individuals with post-stroke language impairment. We specifically consider fundamental principles regarding the optimal spacing of learning trials that have been shown to reliably operate in neurotypical adults, across a wide range of language domains. We report on two studies that examine whether or not these principles also apply in language re-learning and retention for individuals with acquired deficits in written language production. Study 1 compared distributed vs. clustered training schedules, while Study 2 examined—for the first time in the context of re-learning—the relationship between the spacing of training trials and the retention period. This investigation revealed that, despite significant cognitive deficits and brain lesions, remarkably similar principles govern re-learning and retention in the lesioned brain as have been found to apply in neurologically healthy individuals. These results allow us to begin to integrate our understanding of recovery with the broader literature on learning and memory and have implications for the optimal organization of rehabilitation. Specifically, the findings raise questions regarding the traditional compression of rehabilitation within relatively short time windows.

Investigating Fast Mapping Task Components: No Evidence for the Role of Semantic Referent nor Semantic Inference in Healthy Adults.

Fast mapping (FM) is an incidental learning process that is hypothesized to allow rapid, cortical-based memory formation, independent of the normal, hippocampally dependent episodic memory system. It is believed to underlie the rapid vocabulary learning in infants that occurs separately from intentional memorisation strategies. Interest in adult FM learning was stimulated by a report in which adults with amnesia following hippocampal damage showed a normal ability to learn new object-name associations after an incidental FM task, despite their impaired memory under a conventional intentional memorization task. This remarkable finding has important implications for memory rehabilitation, and has led to a number of neuropsychological and neuroimaging studies in other patients and controls. Given this growing interest in adult FM, we conducted four behavioural experiments with healthy adults (N = 24 young or older adults in Experiments 1–3 using within-participant designs; N = 195 young adults in Experiment 4 using a between-participant design) that attempted to dissect which component(s) of the FM task are important for memory. Two key components of the FM task have been claimed to support FM learning: (1) provision of a known semantic referent and (2) requirement that the new association be inferred. Experiment 1 provided no evidence that removing the semantic referent impaired memory performance, while Experiment 2 provided no evidence that removing the semantic inference impaired performance. Experiment 3 was a replication of Experiment 2 with older participants, based on the hypothesis (from studies of amnesic individuals) that FM would be more effective following the hippocampal atrophy typical of increasing age, but again found no evidence that semantic inference is beneficial. Given potential concerns about contamination between tasks when each participant performed multiple variants of the FM task, we ran a final between-participant design in which each participant only ever did one condition. Despite 80% power and despite being able to detect better memory following intentional memorization in the explicit encoding (EE) control condition than in each of the FM conditions, we again found no evidence of differences between any FM conditions. We conclude that there is no evidence that the components hypothesized to be critical for FM are relevant to healthy adults.

Narrative construction is intact in episodic amnesia

Autobiographical remembering and future imagining overlap in their underlying psychological and neurological mechanisms. The hippocampus and surrounding regions within the medial temporal lobes (MTL), known for their role in forming and maintaining autobiographical episodic memories, are also thought to play an essential role in fictitious and future constructions. Amnesic individuals with bilateral hippocampal damage cannot reconstruct their past personal experiences and also have severe deficits in the ability to construct coherent fictitious or future narratives. However, it is not known whether this impairment reflects a failure to generate details from autobiographical episodic memory to populate personal narratives or an inability to bind such details into coherent narratives. We show that four individuals with hippocampal damage and episodic amnesia can construct narratives when the relevant details of the story are provided in a picture book and that their narratives maintain overall coherence on several measures. These findings indicate that individuals with hippocampal damage can bind details into coherent narratives when details are available to them. We conclude that the hippocampal system instead likely plays a role in the generation of details from which narratives are constructed.

Using future thinking to reduce temporal discounting: Under what circumstances are the medial temporal lobes critical?

The capacity to envision the future plays an important role in many aspects of cognition, including our ability to make optimal, adaptive choices. Past work has shown that the medial temporal lobe (MTL) is necessary for decisions that draw on episodic future thinking. By contrast, little is known about the role of the MTL in decisions that draw on semantic future thinking. Accordingly, the present study investigated whether the MTL contributes to one form of decision making, namely intertemporal choice, when such decisions depend on semantic consideration of the future. In an intertemporal choice task, participants must select either a smaller amount of money that is available in the present or a larger amount of money that would be available at a future date. Amnesic individuals with MTL damage and healthy control participants performed such a task in which, prior to making a choice, they engaged in a semantic generation exercise, wherein they generated items that they would purchase with the future reward. In experiment 1, we found that, relative to a baseline condition involving standard intertemporal choice, healthy individuals were more inclined to select a larger, later reward over a smaller, present reward after engaging in semantic future thinking. By contrast, amnesic participants were paradoxically less inclined to wait for a future reward following semantic future thinking. This finding suggests that amnesics may have had difficulty “tagging” the generated item(s) as belonging to the future. Critically, experiment 2 showed that when the generated items were presented alongside the intertemporal choices, both controls and amnesic participants shifted to more patient choices. These findings suggest that the MTL is not needed for making optimal decisions that draw on semantic future thinking as long as scaffolding is provided to support accurate time tagging. Together, these findings stand to better clarify the role of the MTL in decision making.

Cueing the personal future to reduce discounting in intertemporal choice: Is episodic prospection necessary?

How does the ability to imagine detailed future experiences (i.e., episodic prospection) contribute to choices between immediate and delayed rewards? Individuals with amnesia do not show abnormally steep discounting in intertemporal choice, suggesting that neither medial temporal lobe (MTL) integrity nor episodic prospection is required for the valuation of future rewards (Kwan et al. (), Hippocampus, 22:1215-1219; Kwan et al. (2013), J Exp Psychol, 142:1355-1369 2013). However, hippocampally mediated episodic prospection in healthy adults reduces the discounting of future rewards (Peters and Büchel (2010), Neuron, 66:138-148; Benoit et al. (2011), J Neurosci, 31:6771-6779), raising the possibility that MTL damage causes more subtle impairments to this form of decision-making than noted in previous patient studies. Intertemporal choice appears normal in amnesic populations, yet they may be unable to use episodic prospection to adaptively modulate the value assigned to future rewards. To investigate how the extended hippocampal system, including the hippocampus and related MTL structures, contributes to the valuation of future rewards, we compared the performance of six amnesic cases with impaired episodic prospection to that of 20 control participants on two versions of an intertemporal choice task: a standard discounting task, and a cued version in which cues prompted them to imagine specific personal future events temporally contiguous with the receipt of delayed rewards. Amnesic individuals' intertemporal choices in the standard condition were indistinguishable from those of controls, replicating previous findings. Surprisingly, performance of the amnesic cases in the cued condition indicates that amnesia does not preclude flexible modulation of choices in response to future event cues, even in the absence of episodic prospection. Cueing the personal future to modulate decisions appears to constitute a less demanding or a qualitatively different (e.g., personal semantic) form of prospection that is not as sensitive to MTL damage as prospective narrative generation.

Dissociations in future thinking following hippocampal damage: Evidence from discounting and time perspective in episodic amnesia.

Recollecting past experiences and imagining future experiences activate a common set of brain regions that includes the hippocampus (Schacter, Addis, & Buckner, 2007), and both functions are impaired in people with compromised hippocampal function (Klein, Loftus, & Kihlstrom, 2002; Tulving, 1985). These findings indicate a role for the hippocampus that extends beyond declarative memory. However, a case study revealed that a person with extensive medial temporal lobe (MTL) damage and episodic amnesia was able to forgo smaller, immediate rewards for a larger future payoff to a degree similar to control participants (Kwan et al., 2012). This finding suggests that typical regard for the future does not depend on hippocampal integrity. To test this hypothesis, the current study examined the nature and limits of the role of the hippocampus in future thinking and decision making in amnesic individuals with hippocampal damage and associated impairments in episodic memory and future imagining. The amnesic individuals were administered a delay discounting task to assess valuation of future rewards, a probability discounting task to assess risk taking, and the Zimbardo Time Perspective Inventory to assess personal orientation toward the past, present, and future. Comparisons with demographically matched controls indicated that aspects of temporal thought and future-oriented decision making are preserved in individuals with hippocampal amnesia despite their inability to imagine themselves in detailed future events. Thus, even extensive MTL damage and the resulting episodic amnesia do not preclude prudent decision making, including consideration of future financial outcomes and personal identification with the past and future.

Models of recognition, repetition priming, and fluency: Exploring a new framework.

We present a new modeling framework for recognition memory and repetition priming based on signal detection theory. We use this framework to specify and test the predictions of 4 models: (a) a single-system (SS) model, in which one continuous memory signal drives recognition and priming; (b) a multiple-systems-1 (MS1) model, in which completely independent memory signals (such as explicit and implicit memory) drive recognition and priming; (c) a multiple-systems-2 (MS2) model, in which there are also 2 memory signals, but some degree of dependence is allowed between these 2 signals (and this model subsumes the SS and MS1 models as special cases); and (d) a dual-process signal detection (DPSD1) model, 1 possible extension of a dual-process theory of recognition (Yonelinas, 1994) to priming, in which a signal detection model is augmented by an independent recollection process. The predictions of the models are tested in a continuous-identification-with-recognition paradigm in both normal adults (Experiments 1-3) and amnesic individuals (using data from Conroy, Hopkins, & Squire, 2005). The SS model predicted numerous results in advance. These were not predicted by the MS1 model, though could be accommodated by the more flexible MS2 model. Importantly, measures of overall model fit favored the SS model over the others. These results illustrate a new, formal approach to testing theories of explicit and implicit memory.

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.

Activating the Medial Temporal Lobe during Oddity Judgment for Faces and Scenes

Impairments in visual discrimination beyond long-term declarative memory have been found in amnesic individuals, with hippocampal lesions resulting in deficits in scene discrimination and perirhinal cortex damage affecting object discrimination. To complement these findings, the present functional magnetic resonance imaging study found that in healthy participants oddity judgment for novel trial-unique scenes, compared with face or size oddity, was associated with increased posterior hippocampus and parahippocampal cortex activity. In contrast, perirhinal and anterior hippocampus activity was observed during unfamiliar trial-unique face oddity judgment, when contrasted with scene or size oddity tasks. Activity in all of these regions decreased as the stimuli were repeated across trials, reflecting the participants' increasing familiarity with the stimuli. This change was significant in all areas, with the exception of the perirhinal cortex, right anterior hippocampus, and to a lesser extent the left anterior hippocampus during face oddity judgment. One possibility is that the activity in these regions may not reflect entirely episodic memory encoding but, in part, processes beyond the mnemonic domain. Thus, the perirhinal cortex, and possibly anterior hippocampus, may play a more generic role in the discrimination and processing of objects.

Trace Eyeblink Conditioning in Abstinent Alcoholic Individuals: Effects of Complex Task Demands and Prior Conditioning.

Chronic misuse of alcohol affects an integrated neural circuit supporting the formation of associative memories acquired during eyeblink classical conditioning (R. McGlinchey-Berroth et al., 1995). The authors of this study investigated single-cue trace conditioning in amnesic and nonamnesic abstinent alcoholic individuals who either were or were not trained in a single-cue delay conditioning task. Overall, untrained alcoholic participants were severely impaired in acquisition, and alcoholic participants previously trained in single-cue delay conditioning performed similarly to untrained control participants. Individual performance in acquisition varied significantly within task but was relatively stable between the trace and delay tasks; there were nonamnesic and amnesic alcoholic participants who acquired responses at a normal rate in both delay and trace conditioning. The similarity of performances in delay and trace conditioning suggests a common source of impairment across both tasks.

Learning About Categories in the Absence of Training: Profound Amnesia and the Relationship Between Perceptual Categorization and Recognition Memory

Previous evidence suggests that amnesics can categorize stimuli as well as normal individuals but are significantly worse at recognizing those stimuli. In an extreme case, a profoundly amnesic individual, E.P., was found to have near-normal categorization, yet, unlike most amnesics, was unable to recognize better than chance. This evidence has been used to argue against the possibility that a common memory system underlies these cognitive processes. However, we provide evidence that the experimental procedures typically used to test amnesic individuals may be flawed in that initial exposure to category members may be unnecessary to observe accurate categorization of test stimuli. We experimentally “induced” profound amnesia in normal individuals by telling them they had viewed subliminally presented stimuli, which were never actually presented. Using the same experimental paradigm used to test amnesics, we observed that participants' recognition performance was completely at chance, as should be expected, yet categorization performance was quite good.