Medial Temporal Lobe Lesions Research Articles

The congruence of interoceptive predictions and hippocampal-related memory

Interoceptive deficits are associated with medial temporal lobe (MTL) lesions, and especially the hippocampus, which may relate to interoception's reliance upon predictive coding and hence on mnemonic processes. Here, we develop a new task to assess interoceptive predictions and assess their dependence upon MTL memory systems. Healthy participants were asked to imagine and predict what they would feel like across nine interoceptive situations. Later, each situation was physically experienced, and participants reported what they actually felt. An index of predictive congruence was derived and correlated with a neuropsychological measure of hippocampal dependent learning and memory (HDLM), finding that more accurate predictions were associated with better HDLM (Cohen's d = 0.5). We suggest the MTL, and in particular the hippocampus, generates contextually appropriate episodic memories, providing a predictive framework for interpreting afferent bodily neurohormonal signals. The loss of this capacity may account for the profound interoceptive deficits observed following MTL lesions.

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.

Disentangling Hippocampal and Amygdala Contribution to Human Anxiety-Like Behavior.

Anxiety comprises a suite of behaviors to deal with potential threat and is often modeled in approach–avoidance conflict tasks. Collectively, these tests constitute a predominant preclinical model of anxiety disorder. A body of evidence suggests that both ventral hippocampus and amygdala lesions impair anxiety-like behavior, but the relative contribution of these two structures is unclear. A possible reason is that approach–avoidance conflict tasks involve a series of decisions and actions, which may be controlled by distinct neural mechanisms that are difficult to disentangle from behavioral readouts. Here, we capitalize on a human approach–avoidance conflict test, implemented as computer game, that separately measures several action components. We investigate three patients of both sexes with unspecific unilateral medial temporal lobe (MTL) damage, one male with selective bilateral hippocampal (HC), and one female with selective bilateral amygdala lesions, and compare them to matched controls. MTL and selective HC lesions, but not selective amygdala lesions, increased approach decision when possible loss was high. In contrast, MTL and selective amygdala lesions, but not selective HC lesions, increased return latency. Additionally, selective HC and selective amygdala lesions reduced approach latency. In a task targeted at revealing subjective assumptions about the structure of the computer game, MTL and selective HC lesions impacted on reaction time generation but not on the subjective task structure. We conclude that deciding to approach reward under threat relies on hippocampus but not amygdala, whereas vigor of returning to safety depends on amygdala but not on hippocampus.SIGNIFICANCE STATEMENT Approach–avoidance conflict tests are widely investigated in rodents, and increasingly in humans, to understand the neural basis of anxiety-like behavior. However, the contribution of the most relevant brain regions, ventral hippocampus and amygdala, is incompletely understood. We use a human computerized test that separates different action components and find that hippocampus, but not amygdala, lesions impair approach decisions, whereas amygdala, but not hippocampus, lesions impair the vigor of return to safety.

Surgical outcomes of temporal lobe epilepsy in children

Objective To explore the surgical treatment and outcomes of temporal lobe epilepsy in children. Methods A retrospective analysis was conducted on 21 children with temporal lobe epilepsy admitted to Department of Neurosurgery, Children's Hospital Affiliated to Capital Institute of Pediatrics from September 2016 to June 2018. Individualized surgical treatment plan was formulated according to the semeiology, imaging and electroneurophysiological findings of the children. Standard anterior temporal lobectomy was undergone in 13 cases, enlarged resection of temporal lobe lesion in 3, selective hippocampal amygdala resection in 2, simple resection of medial temporal lobe lesion in 1, vascular malformation resection in 1, and anterior temporal lobe resection plus frontal lobe nodule resection in 1. All patients were followed up clinically after operation. The follow-up included cranial MRI, electroencephalogram and Engle rating. Results All 21 patients underwent successful operation. No serious complications occurred after surgery. The pathological results were mixed neuronal-glial tumor in 14 cases, pleomorphic xanthoastrocytoma in 1, hippocampal sclerosis in 3, focal cortical dysplasia IIb in 1, tuberous sclerosis in 1, and cerebral arteriovenous malformation in 1. The follow-up duration of 21 patients was 18.0±5.9 months (9-30 months). A review of head MRI showed that all tumors were completely resected and no recurrence was seen of the patients with tumor. A review of the EEG showed that there was still a large amount of epileptic discharges in the temporal lobe of 1 patient, and the epileptic discharges of the remaining 20 cases were significantly reduced or disappeared compared with preoperative conditions. Eighteen patients were followed up for more than 12 months. Up to the last follow-up, 17 cases were classified as Engle Ⅰ and 1 as Engle Ⅳ. Conclusion Individualized surgical procedures based on comprehensive assessment of the semeiology, imaging and electroneurophysiology of children with temporal lobe epilepsy could lead to good outcomes. Key words: Epilepsy; Temporal lobe; Child; Neurosurgical procedures; Treatment outcome

A differential role for human hippocampus in novelty and contextual processing: Implications for P300.

The role of the hippocampus in P300 has long been debated. Here, we present a theoretical framework that elucidates hippocampal contributions to scalp P300 based on intracranial and lesion research combined with emerging evidence on the role of the hippocampus in rapid statistical learning, memory, and novelty processing. The P300 has been divided in two subcomponents: a fronto-central P3a related to novelty and distractor processing, and a parietal P3b related to target detection. Interest in a role for hippocampus in scalp P300 was sparked by P3-like ERPs measured intracranially in human hippocampus. Subsequent medial temporal lobe lesion studies show intact scalp P3b, indicating that the hippocampus is not critical for P3b. This contrasts with the scalp P3a, which was significantly diminished in human patients with lesions in the posterior hippocampus. This suggests a differential role for hippocampus in P3a and P3b. Our framework purports that the hippocampus plays a central role in distractor processing that leads to P3a generation in cortical regions. We also propose that the hippocampus is involved at the end of the cognitive episode for both P3a and P3b implementing contextual updating. P3-like ERPs measured in hippocampus may reflect input signals from cortical regions implementing updates based on the outcome of cognitive processes underlying scalp P3, enabling a model update of the environment facilitated by the hippocampus. Overall, this framework proposes an active role for the hippocampus in novelty processing leading up to P3a generation, followed by contextual updating of the outcome of both scalp P3a and P3b.

Spared Perception of the Structure of Scenes after Hippocampal Damage

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

Remote spatial and autobiographical memory in cases of episodic amnesia and topographical disorientation

A number of theories have postulated that there is a strong relationship between episodic memory and spatial processes mediated by the hippocampus. Evidence for episodic amnesia following damage to the medial temporal lobes is extensive, but less is known about the types of spatial memory affected by damage to these regions. In this study, we compared episodic memory with detailed scene memory, landmark recognition and schematic (map-based) spatial memory in a group of individuals with amnesia related to damage to the medial temporal lobes (MTL) including the hippocampus. We compared their performance to matched controls, and to an individual with topographical disorientation, a selective spatial memory deficit relating to more posterior temporal and occipital lobe damage. For individuals with MTL lesions, impairments to scene memory were comparable to those in episodic memory. Landmark recognition was impaired only for less familiar landmarks, and schematic spatial memory was not impaired compared to controls. Despite the absence of hippocampal damage, the individual with topographical disorientation, like the MTL amnesic patients, demonstrated impairments to scene memory and recognition of less familiar landmarks, and intact schematic spatial memory, but with less severe episodic memory loss. These results highlight the similarities between detailed scene memory and episodic memory, including their reliance on the medial temporal lobe, and suggest that more schematic forms of spatial memory may be unaffected by medial temporal damage. In addition, the results suggest that damage to more posterior temporal or occipital regions that leads to spatial memory deficits may entail some impairment to episodic memory even if the hippocampus is spared.

Self-related processing and future thinking: Distinct contributions of ventromedial prefrontal cortex and the medial temporal lobes

Episodic future thinking depends on a core network of regions that involves, in addition to the medial temporal lobes (MTL), the ventromedial prefrontal cortex (vmPFC). Neuroimaging studies suggest that vmPFC is particularly involved when future thinking requires consideration of self-relevant information, but lesion evidence for a special role of vmPFC in constructing self-relevant scenarios is limited. To clarify the involvement of vmPFC in future thinking, eight patients with vmPFC lesions were asked to imagine future events pertaining to the self or to another person, and their performance was contrasted with that of eight patients with MTL lesions. Patients with vmPFC lesions were no more detailed in their description of future events pertaining to the self than of events pertaining to another person. In contrast, like controls, patients with MTL lesions showed a self-benefit, despite impoverished performance overall. These findings accord with evidence from neuroimaging studies and elucidate the distinct contributions of vmPFC and MTL to future thinking.

Japanese Encephalitis Presenting with Unilateral Medial Temporal Lobe Lesion

Japanese Encephalitis Presenting with Unilateral Medial Temporal Lobe Lesion

Absence of an early hippocampal encoding signal after medial temporal lesions: No consequence for the spacing effect.

Immediately repeated meaningful pictures in a continuous recognition task induce a positive frontal potential at about 200-300 ms, which appears to emanate from the medial temporal lobe (MTL) centered on the hippocampus, as concluded from inverse solutions, coherence measurements, and depth electrode recordings in humans. In this study, we tested patients with unilateral MTL lesions due to stroke to verify the provenance of this signal and its association with the spacing effect (SE)-the improved learning of material encountered in spaced rather than massed presentation. We found that unilateral left or right MTL lesions abolished the early frontal MTL-mediated signal but not the spacing effect. We conclude that the SE does not depend on MTL integrity. We suggest that the early frontal signal at 200-300 ms after immediate picture repetition may serve as a direct biomarker of MTL integrity that may be useful in the early stages of diseases like Alzheimer's.

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.

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

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

Eye movements support the link between conscious memory and medial temporal lobe function

When individuals select the recently studied (and familiar) item in a multiple-choice memory test, they direct a greater proportion of viewing time toward the to-be-selected item when their choice is correct than when their choice is incorrect. Thus, for both correct and incorrect choices, individuals indicate that the chosen item is old, but viewing time nevertheless distinguishes between old and new items. What kind of memory supports this preferential viewing effect? We recorded eye movements while participants made three-alternative, forced-choice recognition memory judgments for scenes. In experiment 1 (n = 30), the magnitude of the preferential viewing effect was strongly correlated with measures of conscious, declarative memory: recognition accuracy as well as the difference in confidence ratings and in response times for correct and incorrect choices. In four analyses that minimized the contribution of declarative memory in order to detect a possible contribution from other processes, the preferential viewing effect was absent. In experiment 2, five memory-impaired patients with medial temporal lobe lesions exhibited a diminished preferential viewing effect. These patients also exhibited poor recognition accuracy and reduced differences in confidence ratings and response times for correct and incorrect choices. We propose that the preferential viewing effect is a phenomenon of conscious, declarative memory and is dependent on the medial temporal lobe. The findings support the link between medial temporal lobe function and declarative memory. When the effects of experience depend on the medial temporal lobe, the effects reflect conscious memory.

Spared perception of object geometry and object components after hippocampal damage

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

Neuropsychological Investigations of Human Amnesia: Insights Into the Role of the Medial Temporal Lobes in Cognition.

The past 30 years of research on human amnesia has yielded important changes in our understanding of the role of the medial temporal lobes (MTL) in memory. On the one hand, this body of evidence has highlighted that not all types of memory are impaired in patients with MTL lesions. On the other hand, this research has made apparent that the role of the MTL extends beyond the domain of long-term memory, to include working memory, perception, and future thinking. In this article, we review the discoveries and controversies that have characterized this literature and that set the stage for a new conceptualization of the role of the MTL in cognition. This shift toward a more nuanced understanding of MTL function has direct relevance for a range of clinical disorders in which the MTL is implicated, potentially shaping not only theoretical understanding but also clinical practice. (JINS, 2017, 23, 732-740).

Close but no cigar: Spatial precision deficits following medial temporal lobe lesions provide novel insight into theoretical models of navigation and memory.

Remembering goal locations in one's environment is a critical skill for survival. How this information is represented in the brain is still not fully understood, but is believed to rely in some capacity on structures in the medial temporal lobe. Contradictory findings from studies of both humans and animals have been difficult to reconcile with regard to the role of the MTL, specifically the hippocampus. By assessing impairments observed during navigation to a goal in patients with medial temporal lobe damage we can better understand the role these structures play in such behavior. Utilizing virtual reality and novel analysis techniques, we have more precisely assessed the impact that medial temporal lobe damage has on spatial memory and navigation.

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.

The hippocampus is particularly important for building associations across stimulus domains

The medial temporal lobe (MTL) is critical for binding together different attributes that together form memory for prior episodes, but whether it is preferentially involved in supporting specific types of associations is a topic of much debate. Some have argued that the MTL, specifically the hippocampus, may be specialized for binding information from different stimulus domains (e.g., linking visual and auditory stimuli). In the current study, we examined the role of the MTL in memory for associations within- vs. across-domains. Patients with either selective hippocampal lesions or more extensive MTL lesions studied pairs of items within the same stimulus domain (i.e., image-image or sound-sound pairs) or across different domains (i.e., image-sound pairs). Associative memory was subsequently tested by having participants discriminate between previously studied and rearranged pairs. Compared to healthy controls, the patients were significantly more impaired in the across-domain condition than the within-domain conditions. Similar deficits were observed for patients with hippocampal lesions and those with more extensive MTL lesions, suggesting that the hippocampus itself is particularly important for binding associations across stimulus domains.

Memory for relations in the short term and the long term after medial temporal lobe damage.

A central idea about the organization of declarative memory and the function of the hippocampus is that the hippocampus provides for the coding of relationships between items. A question arises whether this idea refers to the process of forming long-term memory or whether, as some studies have suggested, memory for relations might depend on the hippocampus even at short retention intervals and even when the task falls within the province of short-term (working) memory. The latter formulation appears to place the operation of relational memory into conflict with the idea that working memory is independent of medial temporal lobe (MTL) structures. In this report, the concepts of relational memory and working memory are discussed in the light of a simple demonstration experiment. Patients with MTL lesions successfully learned and recalled two word pairs when tested directly after learning but failed altogether when tested after a delay. The results do not contradict the idea that the hippocampus has a fundamental role in relational memory. However, there is a need for further elaboration and specification of the idea in order to explain why patients with MTL lesions can establish relational memory in the short term but not in long-term memory. © 2017 Wiley Periodicals, Inc.

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

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