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Bilateral Hippocampal Pathology Impairs Topographical and Episodic Memory but not Visual Pattern Matching
Abstract
A virtual reality environment was used to test memory performance for simulated “real-world” spatial and episodic information in a 22-year-old male, Jon, who has selective bilateral hippocampal pathology caused by perinatal anoxia. He was allowed to explore a large-scale virtual reality town and was then tested on his memory for spatial layout and for episodes experienced. Topographical memory was tested by assessing his ability to navigate, recognize previously visited locations, and draw maps of the town. Episodic memory was assessed by testing the retrieval of simulated events which consisted of collecting objects from characters while following a route through the virtual town. Memory for the identity of objects, as well as for where they were collected, from whom, and in what order, was also tested. While the first task tapped simple recognition memory, the latter three tested memory for context. Jon was impaired on all topographical tasks and on his recall of the context-dependent questions. However, his recognition of objects from the virtual town, and of “topographical” scenes (as evaluated by standard neuropsychological tests), was not impaired. These findings are consistent with the view that the hippocampus is involved in navigation, recall of long term allocentric spatial information and context-dependent episodic memory, but not visual pattern matching. Hippocampus 2001;11:715–725. © 2001 Wiley-Liss, Inc.
... Allocentric and egocentric spatial navigation are the two fundamental divisions of spatial memory assessed by VR. Allocentric memory allows the participant to make assertions about the locations of landmarks and objects independent of the participant's position, while egocentric memory relies on the participants' ability to relate where they are in space with the direction they are meant to be traveling (Spiers et al., 2001;Hort et al., 2007). ...
... Allocentric memory was also tested using a virtual town (Spiers et al., 2001). First, participants explored the virtual town and then created a map of the area including the locations of eight significant landmark buildings (Spiers et al., 2001). ...
... Allocentric memory was also tested using a virtual town (Spiers et al., 2001). First, participants explored the virtual town and then created a map of the area including the locations of eight significant landmark buildings (Spiers et al., 2001). Patients' scores were based on the relative error in distance between the landmarks on an ideal map, portraying their exact locations, and their own map. ...
Impairment of spatial memory, including an inability to recall previous locations and navigate the world, is often one of the first signs of functional disability on the road to cognitive impairment. While there are many screening and diagnostic tools which attempt to measure spatial memory ability, they are often not representative of real-life situations and can therefore lack applicability. One potential solution to this problem involves the use of virtual reality (VR), which immerses individuals in a virtually-simulated environment, allowing for scenarios more representative of real-life without any of the associated risks. Here, we review the evidence surrounding the use of VR for the screening and diagnosis of spatial memory impairments, including potential limitations and how it compares to standard neuropsychological tests. We will also discuss the evidence regarding the potential use of VR in the rehabilitation of spatial memory deficits, which has not been well studied, but which could be game-changing if proven successful.
... Most lesion studies support the idea that the MTL (in particular the right hemisphere) is critical for place learning (Abrahams et al. 1997;Holdstock et al. 1999Holdstock et al. , 2000 and goaldirected navigation (Astur et al. 2002;Maguire et al. 2006a;Spiers et al. 2001). In general, damage to this region impairs spatial memory but not object memory (Abrahams et al. 1997;Spiers et al. 2001). ...
... Most lesion studies support the idea that the MTL (in particular the right hemisphere) is critical for place learning (Abrahams et al. 1997;Holdstock et al. 1999Holdstock et al. , 2000 and goaldirected navigation (Astur et al. 2002;Maguire et al. 2006a;Spiers et al. 2001). In general, damage to this region impairs spatial memory but not object memory (Abrahams et al. 1997;Spiers et al. 2001). With respect to navigation, Astur et al. (2002) found that patients with bilateral MTL lesions were unable to locate a hidden platform in a virtual version of the Morris water maze task (see Morris et al. 1982). ...
... With respect to navigation, Astur et al. (2002) found that patients with bilateral MTL lesions were unable to locate a hidden platform in a virtual version of the Morris water maze task (see Morris et al. 1982). Similarly, Spiers et al. (2001) described one patient with bilateral hippocampal pathology who could not navigate towards a location, recognize previously visited locations, or draw maps of a learned virtual reality environment. However, Maguire et al. (2006a) suggested that the hippocampus may be more critical for encoding fine-grained details such as small streets rather than main arteries during navigation. ...
Cognitive neuroscience can provide novel and interesting techniques for investigating spatial and geographic thinking. However, the incorporation of neuroscientific methods still lacks the theoretical motivation necessary for the progression of geography as a discipline. Rather than reflecting a shortcoming of neuroscience, this weakness has developed from previous attempts to establish a positivist approach to behavioral geography. In this chapter, we will discuss the challenges of establishing a positivist approach in behavioral geography and the current drive to incorporate neuroscientific evidence. Towards this end, we review research in geography and neuroscience. Here, we focus specifically on navigation and large-scale spatial thinking. We argue that research at the intersection of geography and neuroscience would benefit from an explanatory, theory-driven approach rather than a descriptive, exploratory approach. Future collaborations will require additional training for geographers and neuroscientists and the involvement of both disciplines during the early stages of a research program.
... Finally, using an incidental recognition task (visual paired-comparison or object/context-VPC), Bachevalier and colleagues (Bachevalier, Nemanic, & Alvarado, 2015) demonstrated a lack of novelty preference in monkeys with selective hippocampal lesions sustained in adulthood when a familiar object was presented over a new background. Similar findings have also been reported in humans, rabbits, and rodents (Burgess, Maguire, Spiers, & O'Keefe, 2001;Freeman, Weible, Rossi, & Gabriel, 1997;Kennedy & Shapiro, 2004;Kim & Fanselow, 1992;Kim, Lee, & Lee, 2012;Mayes, MacDonald, Donlan, Pears, & Meudell, 1992;Penick & Solomon, 1991;Phillips & LeDoux, 1992;Rudy, Barrientos, & O'Reilly, 2002;Sill & Smith, 2012;Smith & Mizumori, 2006;Pascalis, Hunkin, Bachevalier, & Mayes, 2009;Spiers, Burgess, Hartley, Vargha-Khadem, & O'Keefe, 2001). ...
... Given the critical contribution of the hippocampus in processing object-context associations (Bachevalier et al., 2015;Diana et al., 2007;Eichenbaum, Yonelinas, & Ranganath, 2007;Kim & Fanselow, 1992;Pascalis et al., 2009;Phillips & LeDoux, 1992;Smith & Mizumori, 2006;Spiers et al., 2001), the concurrent discrimination task was modified in a third experiment to assess whether neonatal hippocampal damage would affect learning of the discriminations when the background was made relevant for correct performance on the task. To this end, four new pairs of stimuli and eight new backgrounds were selected for the task. ...
This study examined whether selective neonatal hippocampal lesions in monkeys ( Macaca mulatta ), which left the surrounding cortical areas (parahippocampal cortex) intact, affect contextual learning and memory compared with controls. Monkeys were tested with an automated touch-screen apparatus so that stimuli and contextual cues could be manipulated independently of one another. The data suggest that animals with neonatal hippocampal lesions have sparing of function with regard to contextual learning and memory when (a) contextual information is irrelevant or (b) relevant for good discrimination performance, and (c) when transferring a contextual rule to new discriminations. These findings are at odds with studies examining contextual learning and memory in monkeys with selective adult-onset hippocampal lesions, and those with nonselective neonatal hippocampal lesions, which have demonstrated impairment in contextual learning and memory. Therefore, the sparing of function seen in this study may be attributable to the early nature of the damage and the plastic nature of the infant brain, as well as the intact medial temporal lobe cortical areas as a result of the lesion methodology. Specifically, by removing the hippocampus early in life, before it has begun to function, the parahippocampal (TH/TF) and perirhinal cortices and its interactions with the lateral prefrontal cortex may be able to support context processing throughout life.
... In this case, the influence of a hippocampal lesion becomes particularly evident. In humans, the hippocampal function has been shown to be lateralized, with the right hippocampus linked more to navigationrelated functions compared to the left hippocampus 53,54 . The patients in our study had lesions in the right medial temporal lobe and they exclusively relied on the left medial temporal lobe for hippocampal computations. ...
Efficient navigation is supported by a cognitive map of space. The hippocampus plays a key role for this map by linking multimodal sensory information with spatial memory representations. However, in human navigation studies, the full range of sensory information is often unavailable due to the stationarity of experimental setups. We investigated the contribution of multisensory information to memory-guided spatial navigation by presenting a virtual version of the Morris water maze on a screen and in an immersive mobile virtual reality setup. Patients with hippocampal lesions and matched controls navigated to memorized object locations in relation to surrounding landmarks. Our results show that availability of multisensory input improves memory-guided spatial navigation in both groups. It has distinct effects on navigational behaviour, with greater improvement in spatial memory performance in patients. We conclude that congruent multisensory information shifts computations to extrahippocampal areas that support spatial navigation and compensates for spatial navigation deficits.
... We posit that specific spectrotemporal information embedded in the sound drive this specificity. The hippocampus is positioned to process temporal information of sensory inputs ( Aronov et al., 2017, Eichenbaum, 2014, as hippocampal lesions can impair memory for the temporal order of events in both animals ( Kesner et al., 2005, DeVito et al., 2009 ) and humans ( Mayes et al., 2001, Spiers et al., 2001. When learning to associate specific time intervals with a given stimulus, the hippocampus is essential for discriminating minute temporal differences in rodents ( Jacobs et al., 2013 ). ...
Despite its prominence in learning and memory, hippocampal influence in early auditory processing centers remains unknown. Here, we examined how hippocampal activity modulates sound-evoked responses in the auditory midbrain and thalamus using optogenetics and functional MRI (fMRI) in rodents. Ventral hippocampus (vHP) excitatory neuron stimulation at 5 Hz evoked robust hippocampal activity that propagates to the primary auditory cortex. We then tested 5 Hz vHP stimulation paired with either natural vocalizations or artificial/noise acoustic stimuli. vHP stimulation enhanced auditory responses to vocalizations (with a negative or positive valence) in the inferior colliculus, medial geniculate body, and auditory cortex, but not to their temporally reversed counterparts (artificial sounds) or broadband noise. Meanwhile, pharmacological vHP inactivation diminished response selectivity to vocalizations. These results directly reveal the large-scale hippocampal participation in natural sound processing at early centers of the ascending auditory pathway. They expand our present understanding of hippocampus in global auditory networks.
... Normal animals often spend more time in the quadrant where the platform was previously positioned than in the other quadrants in this section of the probe trials in water-maze tests. The probe trial measures the strength of spatial learning, which is the closest human analog to episodic memory, and the testing procedures utilized during the four days of locating the hidden platform provide a measure of hippocampal-dependent spatial reference memory (Jeltsch et al., 2001;Spiers et al., 2001). ...
Background: Viagra is a white crystalline powder, with a molecular weight of 666.7, covered with a blue shell and takes the shape of a diamond or a rhombus. Male Swiss white mice were used to study the effect of Viagra on learning behavior, some neurotransmitters, and indicators of oxidative stress. In the Shuttle box, Water-maze, and T-Maze tests, Viagra -treated males showed decreased body weight and improved learning behavior. Aim: The purpose of this study is to determine the effect of Viagra oral administration on learning behavior, neurotransmitters, and oxidative markers in male mice. Methods: In this study, Dopamine (DA), 5-hydroxyanisole (5-HA) and acetylcholinesterase (AchE) were all downregulated. Biochemical assays such as glutathione (GSH) and enzyme activity of Glutathione S Transferase (GST), Catalase (CAT), and superoxide dismutase (SOD) and Thiobarbituric acid relative substances (TBARS) was studied. Results: The results of this study show that the shuttle box test, Viagra exposure, water maize test, and t-maize test were all associated (p
... Studies in healthy adults frequently focus on the hippocampus as the structure supporting map formation and use (Ekstrom & Isham, 2017;Ekstrom & Ranganath, 2018;He & Brown, 2019), although neuroimaging studies also point to posterior brain regions such as the parahippocampal and retrosplenial cortices (e.g., Epstein et al., 2017), as well as to dynamic patterns of cortico-hippocampal connectivity (e.g., Weisberg & Ekstrom, 2021). Tasks assessing familiar spatial contexts or routes emphasize extra-hippocampal regions, including the posterior parietal cortex, posterior cingulate, retrosplenial cortex, and parahippocampal cortex (Ciaramelli et al., 2010;Rosenbaum et al., 2000Rosenbaum et al., , 2004, whereas the acquisition and recall of novel routes appear to engage both hippocampal and extra-hippocampal regions (DeIpolyi et al., 2007;Spiers et al., 2001). The hippocampus is needed if the task requires retrieval of details contained within remote spatial representations (Maguire et al., 2006;Rosenbaum et al., 2000Rosenbaum et al., , 2005 or flexible use of those details . ...
Early cognitive neuroscientific research revealed that the hippocampus is crucial for spatial navigation in rodents, and for autobiographical episodic memory in humans. Researchers quickly linked these streams to propose that the human hippocampus supports memory through its role in representing space, and research on the link between spatial cognition and episodic memory in humans has proliferated over the past several decades. Different researchers apply the term “spatial” in a variety of contexts, however, and it remains unclear what aspect of space may be critical to memory. Similarly, “episodic” has been defined and tested in different ways. Naturalistic assessment of spatial memory and episodic memory (i.e., episodic autobiographical memory) is required to unify the scale and biological relevance in comparisons of spatial and mnemonic processing. Limitations regarding the translation of rodent to human research, human ontogeny, and inter‐individual variability require greater consideration in the interpretation of this literature. In this review, we outline the aspects of space that are (and are not) commonly linked to episodic memory, and then we discuss these dimensions through the lens of individual differences in naturalistic autobiographical memory. Future studies should carefully consider which aspect(s) of space are being linked to memory within the context of naturalistic human cognition.
This article is categorized under: Psychology > Memory
... Longitudinal studies examining behavioral and imaging data are needed to confirm the causal relationship between APOE4 status and navigational strategies. Relatedly, it was found that wayfinding performance, which is supported in part by the hippocampus (e.g., Konishi et al., 2017;Guderian et al., 2015;Spiers, Burgess, Hartley, Vargha-Khadem, & O'Keefe, 2001), within the mobile game Sea Hero Quest (SHQ) was lower for APOE4 carriers compared with non-APOE4 carriers (Coughlan et al., 2019). ...
Humans show a remarkable capacity to navigate various environments using different navigation strategies, and we know that strategy changes across the life span. However, this observation has been based on studies of small sample sizes. To this end, we used a mobile app-based video game (Sea Hero Quest) to test virtual navigation strategies and memory performance within a distinct radial arm maze level in over 37,000 participants. Players were presented with 6 pathways (3 open and 3 closed) and were required to navigate to the 3 open pathways to collect a target. Next, all 6 pathways were made available and the player was required to visit the pathways that were previously unavailable. Both reference memory and working memory errors were calculated. Crucially, at the end of the level, the player was asked a multiple-choice question about how they found the targets (i.e., a counting-dependent strategy vs. a landmark-dependent strategy). As predicted from previous laboratory studies, we found the use of landmarks declined linearly with age. Those using landmark-based strategies also performed better on reference memory than those using a counting-based strategy. These results extend previous observations in the laboratory showing a decreased use of landmark-dependent strategies with age.
... Tous les modèles présentés par la suite ont un point commun : ils basent leurs réflexions sur la présence d'une activation hippocampique dans des tâches spatiales. L'hippocampe semble jouer un double rôle : un rôle mnésique, comme le prouve son activation pendant des tâches de mémoire épisodique (Dickerson et Eichenbaum, 2009) et le déficit mnésique qui est généré par sa lésion (l'amnésie antérograde, soit l'incapacité à rappeler les événements qui sont survenus après la lésion est rapportée dès 1957 par Scoville et Milner) ; un rôle spatial, comme l'indique son activation durant les tâches spatiales (Maguire, Woollett et Spiers, 2006) et les difficultés à résoudre des tâches spatiales que rencontrent les patients amnésiques (Spiers, Burgess, Hartley, Vargha-Khadem, O'Keefe, 2001). ...
Les processus d’intégration d’informations visuelles et proprioceptives jouent un rôle fondamental dans notre aptitude à coordonner nos actions dans l’espace et à maintenir notre stabilité posturale. Des études récentes suggèrent que ces mêmes processus pourraient sous-tendre une capacité apparemment radicalement différente, l’évocation des souvenirs c’est-à-dire la mémoire épisodique. L’implication d’une même structure cérébrale, l’hippocampe, dans le traitement spatial et dans la capacité à récupérer consciemment un moment vécu a conduit à poser l’hypothèse d’un lien neuro-fonctionnel entre ces deux capacités. Cette relation est généralement attribuée à l’existence de représentations mnésiques spatialisées qui coderaient les relations spatiales entre objets (codage allocentré) nécessaires pour reconstituer ensuite un épisode précédemment vécu (Squire & Alvarez, 1995 ; Nadel & Moscovitch, 1998). Cependant la relation entre ces deux capacités pourrait être dépendante non pas de l’existence d’une trace mnésique spatialisée, mais de processus communs (Maguire & Mullaly, 2013). Cette hypothèse permettrait notamment de rendre compte des déficits conjoints de projection épisodique dans le futur et d’incapacité à évoquer des souvenirs observés chez les patients présentant une amnésie antérograde. Des recherches menées au LPNC ont indiqué que le processus de mise à jour égocentrée, qui repose sur l’intégration dynamique des informations proprioceptives et environnementales, pouvait constituer un bon candidat pour ce processus commun. En effet, maximiser un traitement de mise à jour égocentrée à l’apprentissage permet une augmentation des souvenirs à la récupération comparativement à une maximisation d’un traitement allocentré (Gomez, Rousset & Baciu, 2009). En retour, un traitement de mise à jour égocentrée effectué en tâche concurrente produit plus d’interférence sur la récupération de souvenirs qu’un traitement allocentré (Ce rles, Guinet & Rousset, 2015), cet effet n’étant pas présent en mémoire sémantique. Enfin les patients amnésiques montrent un déficit spécifique du traitement de mise à jour égocentrée (Gomez, Rousset, & Charnallet, 2012 ; Gomez, Rousset, Bonniot, Charnallet & Moreaud 2014). L’objectif du projet est d’approfondir l’implication de la mise à jour égocentrée dans la mémoire épisodique. Tout d’abord si les patients présentant une amnésie présentent bien un déficit de projection épisodique dans le futur associé à des troubles spatiaux spécifiques, il est toujours possible d’avancer que le lien est dû à des ségrégations fines de fonctions distinctes dans une même structure, fonction qui serait touchée conjointement par la lésion. Nous chercherons donc à mettre en évidence que, pour des sujets non lésés, la projection épisodique peut être perturbée en interférant en ligne sur les processus d’intégration spatiaux. Enfin ce projet de thèse s’inscrit également dans le cadre d’étud es en cours destinées à évaluer comment l’examen des traitements de mise à jour égocentrée permet de fournir des indices comportementaux pertinents dans l’évaluation de pathologies dégénératives évoluant vers une démence d’Alzheimer.
... The hippocampus contains a modifiable synapsis that provides the acquisition of declarative memory [33], including episodic, semantic, and familiarity-based recognition memory [34], and spatial learning and memory in animals [35,36] and humans [37,38]. Given that hippocampal pyramidal neurons have >10,000 independently modifiable synapses, the potential for information storage by synaptic modification, neuromodulation, and other priming events is enormous [39]. ...
Synaptic plasticity is a cellular process involved in learning and memory by which specific patterns of neural activity adapt the synaptic strength and efficacy of the synaptic transmission. Its induction is governed by fine tuning between excitatory/inhibitory synaptic transmission. In experimental conditions, synaptic plasticity can be artificially evoked at hippocampal CA1 pyramidal neurons by repeated stimulation of Schaffer collaterals. However, long-lasting synaptic modifications studies during memory formation in physiological conditions in freely moving animals are very scarce. Here, to study synaptic plasticity phenomena during recognition memory in the dorsal hippocampus, field postsynaptic potentials (fPSPs) evoked at the CA3-CA1 synapse were recorded in freely moving mice during object-recognition task performance. Paired pulse stimuli were applied to Schaffer collaterals at the moment that the animal explored a new or a familiar object along different phases of the test. Stimulation evoked a complex synaptic response composed of an ionotropic excitatory glutamatergic fEPSP, followed by two inhibitory responses, an ionotropic, GABAA-mediated fIPSP and a metabotropic, G-protein-gated inwardly rectifying potassium (GirK) channel-mediated fIPSP. Our data showed the induction of LTP-like enhancements for both the glutamatergic and GirK-dependent components of the dorsal hippocampal CA3-CA1 synapse during the exploration of novel but not familiar objects. These results support the contention that synaptic plasticity processes that underlie hippocampal-dependent memory are sustained by fine tuning mechanisms that control excitatory and inhibitory neurotransmission balance.
... The details of test are described elsewhere [2,5]. The testing procedure used during the four days of locating the hidden platform provides a measure of hippocampal-dependent spatial reference memory [20], whereas the probe trials of water maze test (measured on 5 th day of the test for 120 s in which the platform was removed from the pool) measures the strength of spatial learning or memory recall, the closest parallel to episodic memory in humans [21]. ...
The present study explores the neuroprotective effects of the natural food product Cinnamomum cassia or Cinnamon (CIN) on lithium pilocarpine (Li-Pc) induced SE in experimental rats to look into a possibility of it being used as antiepileptic drug. Recent studies have shown significant potential of pharmacological, prophylactic or therapeutic use of CIN in many beneficial activities in the body. The animals received CIN pre-treatment before induction of SE. Besides the severity of the seizures, other parameters like cognitive behavioral dysfunction, hippocampal oxidative stress and histological abnormalities in the hippocampus of animals induced with SE by lithium (Li) in 3 mEq/ml/kg dose, i.p. followed 20 h later by pilocarpine (Pc) in 20 mg/ml/kg dose, s.c. CIN was administered intraperitoneally at the doses of 25 and 50 mg/mL/kg, 30 minutes before Pc injection. Mortality (if any) within 24 hours was also recorded. Ethical approval was obtained from the Ethics Committee Review Board of the College of Pharmacy of King Saud University, Riyadh, Saudi Arabia. Treatment with CIN significantly ameliorated the frequency and severity of epileptic seizures in a dose-dependent manner. The cognitive dysfunctions were improved, hippocampal oxidative stress was ameliorated and neuronal cell loss in the hippocampus were also attenuated significantly and dose-dependently by CIN. Possible therapeutic application of CIN as an antiepileptic and as an antioxidant for the treatment of SE has a great potential and warrants further studies.
... In this part of probe trials in water-maze test, normal animals typically spent more time in the quadrant where the platform had been previously located than in the other quadrants. The testing procedures used during the four days of locating the hidden platform provide a measure of hippocampal-dependent spatial reference memory, while the probe trial is a measure of the strength of spatial learning, the closest parallel to episodic memory in humans [27,28]. ...
... The details of test are described elsewhere [2,7]. The testing procedure used during the four days of locating the hidden platform provides a measure of hippocampal-dependent spatial reference memory [28], whereas the probe trials of water maze test (measured on 5th day of the test for 120 s in which the platform was removed from the pool) measures the strength of spatial learning or memory recall, the closest parallel to episodic memory in humans [29]. ...
The lithium-pilocarpine (Li-Pc) model of status epilepticus (SE) is most convenient and is frequently used for pathophysiological and management strategies in search of new, safe and effective therapeutic agents including the natural remedies for SE. Oral administration of cinnamon (CIN) and curcumin (CUR) can reduce neuroinflammation which is a common feature of neurodegenerative pathophysiological disorders. Although many studies on CUR effects on SE has been undertaken, to our best knowledge no study has been conducted on studying the effect of CIN on SE. The present study explores the neuroprotective effects of natural food products CUR and CIN on Li-Pc induced SE in rats. SE was induced in experimental rats using lithium – pilocarpine model. Besides control groups, the animals were also grouped as treatment groups which received CIN and CUR pre-treatment before induction of SE. Besides severity of the seizures, cognitive dysfunctions, oxidative stress parameters were also estimated in the forebrain tissue of all group of animals. Treatment with CIN and CUR significantly ameliorated the frequency and severity of epileptic seizures in a dose-dependent manner. The cognitive dysfunctions as well as the oxidative stress indices (enzymatic as well as non-enzymatic) were ameliorated significantly and dosedependently by CIN and CUR pre-treatment in the order CUR<CIN in all parameters. Possible therapeutic application of CIN and CUR as antiepileptic and as antioxidant for the treatment of SE has a great potential and warrants further studies
... On an electronic time, recorder, time spent in each quadrant (within 120 s of the probe test period) was recorded Probe trials in a watermaze test often show that normal animals spend a lot of time in the quadrant where the platform was previously situated. Tests conducted over a four-day period to discover where the platform was hidden provide an indication of hippocampal-dependent spatial reference memory, while the probe trial measures the strength of spatial learning, the human brain's closest equivalent to episodic memory (Jeltsch et al., 2001, Spiers et al., 2001. ...
Arsenic is an element that raises much concern from the both environmental and human health. The effects of As on learning behavior, neurotransmitters, and oxidative stress indicators were studied in male Swiss white mice. The purpose of this study was to explore into the preliminary work described concerning memory, biochemical changes, and learning impairment in mice exposed to arsenic. The study results in the Shuttle box, Water-maze, T-Maze tests and body weight measurements, As-treated males demonstrated decreased body weight and learning behavior. Dopamine, DA, serotonin, 5-HA, and cholinesterase, AchE levels were all decreased. When compared to the control, GSH and the enzymes GST, CAT, and SOD activity were decreased, while TBARS activity was raised. This study concludes as the essential reasons that explain the causes of As influence on learning and other data, based on the results collected and other previous studies in this field. In general, additional research is required to determine As negative effects on various elements of human and animal health.
... Optimal navigation will travel the shortest distance to the goal (shortest length of the trajectory), whereas inaccurate navigation will create long paths to the goal (long trajectories). Thus, akin to many other studies (e.g., Spiers, Burgess, Hartley, Vargha-Khadem, & O'Keefe, 2001) we used the length of the trajectory as the simple metric to quantify SA. We considered that video game experience might bias performance, with players familiar with gaming on smartphones and tablets having an advantage in keeping the boat on the path chosen rather than colliding with obstacles. ...
Navigation ability varies widely across humans. Prior studies have reported that being younger and a male has an advantage for navigation ability. However, these studies have generally involved small numbers of participants from a handful of western countries. Here, we review findings from our project Sea Hero Quest, which used a video game for mobile and tablet devices to test 3.9 million people on their navigation ability, sampling across every nation-state and from 18 to 99 years of age. Results revealed that the task has good ecological validity and across all countries sufficiently sampled (N = 63), age is linked to a near-linear decline in navigation ability from the early 20s. All countries showed a male advantage, but this varied considerably and could be partly predicted by gender inequality. We found that those who reported growing up in a city were on average worse at navigating than those who grew up outside cities and that navigation performance helped identify those at greater genetic risk of Alzheimer's disease. We discuss the advantages and challenges of using a mobile app to study cognition and the future avenues for understanding individual differences in navigation ability arising from this research.
... A large body of work in animals and humans has shown that 90 the hippocampus is essential for remembering the temporal order of sequential events (Eichenbaum, 2013). For example, in humans, the hippocampus is activated when subjects recall the order of objects, and conversely, patients with hippocampal damage have trouble in temporal order judgements (Spiers et al., 2001;Ekstrom and Bookheimer, 2007). In animals, rats with hippocampal damage are impaired at remembering the sequential order of odors (Fortin et 95 al., 2002). ...
An indispensable feature of episodic memory is our ability to temporally piece together different elements of an experience into a coherent memory. Hippocampal "time cells" - neurons that represent temporal information - may play a critical role in this process. While these cells have been repeatedly found in rodents, it is still unclear to what extent similar temporal selectivity exists in the human hippocampus. Here we show that temporal context modulates the firing activity of human hippocampal neurons during structured temporal experiences. We recorded neuronal activity in the human brain while patients of either sex learned predictable sequences of pictures. We report that human time cells fire at successive moments in this task. Furthermore, time cells also signaled inherently changing temporal contexts during empty 10-second gap periods between trials, while participants waited for the task to resume. Finally, population activity allowed for decoding temporal epoch identity, both during sequence learning and during the gap periods. These findings suggest that human hippocampal neurons could play an essential role in temporally organizing distinct moments of an experience in episodic memory.Significance Statement:Episodic memory refers to our ability to remember the "what, where, and when" of a past experience. Representing time is an important component of this form of memory. Here, we show that neurons in the human hippocampus represent temporal information. This temporal signature was observed both when participants were actively engaged in a memory task, as well as during 10s-long gaps when they were asked to wait before performing the task. Furthermore, the activity of the population of hippocampal cells allowed for decoding one temporal epoch from another. These results suggest a robust representation of time in the human hippocampus.
... The discovery of place cells in the hippocampal CA1 area provided first evidence that the hippocampus is involved in place mapping and spatial memory processing (O'Keefe and Dostrovsky, 1971). Several studies have likewise shown the importance of the hippocampus in spatial memory and navigation in humans (Maguire et al., 1996b;Maguire et al., 1996a;Abrahams et al., 1997;Abrahams et al., 1999;Spiers et al., 2001a;Burgess et al., 2002;Bartsch et al., 2010). Lesion experiments confirmed that the hippocampus plays a role in spatial navigation, a cognitive function that can be analyzed with the help of the Morris water maze (MWM) test (Morris et al., 1982;Morris, 1984). ...
Ciliary neurotrophic factor (Cntf) acts as a differentiation and survival factor for different types of neurons and glial cells. It is expressed by peripheral Schwann cells and astrocytes in the central nervous system and mediates its effects via a receptor complex involving CntfRα, LifRß and gp130, leading to downstream activation of Stat3. Recent studies by our group have shown that Cntf modulates neuronal microtubule dynamics via Stat3/stathmin interaction. In a mouse model for motor neuron disease, i.e. pmn, Cntf is able to rescue axonal degeneration through Stat3/stathmin signaling. While these findings suggest a role of Cntf in controlling axonal functions in the neuromuscular system, additional data indicate that Cntf might also play a role in synaptic plasticity in the hippocampus. Electrophysiological recordings in hippocampal organotypic cultures and acute slices revealed a deficit in long-term potentiation (LTP) in Cntf -/- mice. This deficit was rescued by 24 h stimulation with Cntf, combined with an acute application of Cntf during LTP-measurements indicating that Cntf is both necessary and sufficient for hippocampal LTP, and possibly synaptic plasticity. Therefore, Cntf knockout mice were investigated to elucidate this possible role of Cntf in hippocampal LTP and synaptic plasticity. First, we validated the presence of Cntf in the target tissue: in the hippocampus, Cntf was localized in Gfap-positive astrocytes surrounding small blood vessels in the fissure and in meningeal areas close to the dentate gyrus. Laser micro-dissection and qPCR analysis showed a similar distribution of Cntf-coding mRNA validating the obtained immunofluorescent results. Despite the strong LTP deficit in organotypic cultures, in vivo behavior of Cntf -/- mice regarding hippocampus-dependent learning and anxiety-related paradigms was largely inconspicuous. However, western blot analysis of hippocampal organotypic cultures revealed a significant reduction of pStat3 levels in Cntf -/- cultures under baseline conditions, which in turn were elevated upon Cntf stimulation. In order to resolve and examine synaptic structures we turned to in vitro analysis of cultured hippocampal neurons which indicated that pStat3 is predominantly located in the presynapse. In line with these findings, presynapses of Cntf -/- cultures were reduced in size and when in contact to astrocytes, contained less pStat3 immunoreactivity compared to presynapses in wildtype cultures. In conclusion, our findings hypothesize that despite of a largely inconspicuous behavioral phenotype of Cntf -/- mice, Cntf appears to have an influence on pStat3 levels at hippocampal synapses. In a next step these two key questions need to be addressed experimentally: 1) is there a compensatory mechanism by members of the Cntf family, possibly downstream of pStat3, which explains the in vivo behavioral results of Cntf -/- mice and can likewise account for the largely inconspicuous phenotype in CNTF-deficient humans? 2) How exactly does Cntf influence LTP through Stat3 signaling? To unravel the underlying mechanism further experiments should therefore investigate whether microtubule dynamics downstream of Stat3 and stathmin signaling are involved in the Cntf-induced modulation of hippocampal synaptic plasticity, similar to as it was shown in motoneurons.
... The field of learning and memory has historically utilized a variety of methods to assess spatial navigation during learning and memory tasks, ranging from Tolman's sunburst maze to test rodents (Tolman, 1948) to the virtual reality techniques used in more recent human neuroimaging studies (Spiers et al., 2001; see review: Burgess et al., 2002). There is a long history of work showing memory decline during normal aging in humans (Salthouse et al., 1989;Cherry et al., 1993;Weaver Cargin et al., 2007; see reviews : Glisky, 2007;Harada et al., 2013;Cohen et al., 2019) and in rodent models (Barnes, 1979;Frick et al., 1995;Bizon et al., 2009; see reviews: Gallagher and Nicolle, 1993;Rodefer and Baxter, 2007;Foster, 2012;Bettio et al., 2017). ...
Rodent aging research often utilizes spatial mazes, such as the water radial-arm-maze (WRAM), to evaluate cognition. The WRAM can simultaneously measure spatial working and reference memory, wherein these two memory types are often represented as orthogonal. There is evidence, however, that these two memory forms yield interference at a high working memory load. The current study systematically evaluated whether the presence of a reference memory component impacts handling of an increasing working memory load. Young and aged female rats were tested to assess whether aging impacts this relationship. Cholinergic projections from the basal forebrain to the hippocampus and cortex can affect cognitive outcomes, and are negatively impacted by aging. To evaluate whether age-related changes in working and reference memory profiles are associated with cholinergic functioning, we assessed choline acetyltransferase activity in these behaviorally-tested rats. Results showed that young rats outperformed aged rats on a task testing solely working memory. The addition of a reference memory component deteriorated the ability to handle an increasing working memory load, such that young rats performed similar to their aged counterparts. Aged rats also had challenges when reference memory was present, but in a different context. Specifically, aged rats had difficulty remembering which reference memory arms they had entered within a session, compared to young rats. Further, aged rats that excelled in reference memory also excelled in working memory when working memory demand was high, a relationship not seen in young rats. Relationships between cholinergic activity and maze performance differed by age in direction and brain region, reflecting the complex role that the cholinergic system plays in memory and attentional processes across the female lifespan. Overall, the addition of a reference memory requirement detrimentally impacted the ability to handle working memory information across young and aged timepoints, especially when the working memory challenge was high; these age-related deficits manifested differently with the addition of a reference memory component. This interplay between working and reference memory provides insight into the multiple domains necessary to solve complex cognitive tasks, potentially improving the understanding of complexities of age- and disease- related memory failures and optimizing their respective treatments.
... A large body of work in animals and humans has shown that 90 the hippocampus is essential for remembering the temporal order of sequential events (Eichenbaum, 2013). For example, in humans, the hippocampus is activated when subjects recall the order of objects, and conversely, patients with hippocampal damage have trouble in temporal order judgements (Spiers et al., 2001;Ekstrom and Bookheimer, 2007). In animals, rats with hippocampal damage are impaired at remembering the sequential order of odors (Fortin et 95 al., 2002). ...
An indispensable feature of episodic memory is our ability to temporally piece together different elements of an experience into a coherent memory. Hippocampal “time cells” – neurons that represent temporal information – may play a critical role in this process. While these cells have been repeatedly found in rodents, it is still unclear to what extent similar temporal selectivity exists in the human hippocampus. Here we show that temporal context modulates the firing activity of human hippocampal neurons during structured temporal experiences. We recorded neuronal activity in the human brain while patients learned predictable sequences of pictures. We report that human time cells fire at successive moments in this task. Furthermore, time cells also signaled inherently changing temporal contexts during empty 10-second gap periods between trials, while participants waited for the task to resume. Finally, population activity allowed for decoding temporal epoch identity, both during sequence learning and during the gap periods. These findings suggest that human hippocampal neurons could play an essential role in temporally organizing distinct moments of an experience in episodic memory.
Significance Statement
Episodic memory refers to our ability to remember the “what, where, and when” of a past experience. Representing time is an important component of this form of memory. Here, we show that neurons in the human hippocampus represent temporal information. This temporal signature was observed both when participants were actively engaged in a memory task, as well as during 10s-long gaps when they were asked to wait before performing the task. Furthermore, the activity of the population of hippocampal cells allowed for decoding one temporal epoch from another. These results suggest a robust representation of time in the human hippocampus.
... Intact hippocampal function is necessary for place learning in a plus-maze task as well (Packard and McGaugh, 1996). Evidence from neuroimaging studies of humans and patients with hippocampal damage further implicates the hippocampus in supporting both place learning and flexible navigation of novel routes and environments (Bohbot et al., 2007;Hartley et al., 2003;Howard et al., 2014;Iaria et al., 2003;Javadi et al., 2019aJavadi et al., , 2019bJavadi et al., 2017;Patai et al., 2019;Spiers et al., 2001aSpiers et al., , 2001bSpiers and Maguire, 2006;Xu et al., 2010). ...
The hippocampus has been firmly established as playing a crucial role in flexible navigation. Recent evidence suggests that dorsal striatum may also play an important role in such goal-directed behaviour in both rodents and humans. Across recent studies, activity in the caudate nucleus has been linked to forward planning and adaptation to changes in the environment. In particular, several human neuroimaging studies have found the caudate nucleus tracks information traditionally associated with that by the hippocampus. In this brief review, we examine this evidence and argue the dorsal striatum encodes the transition structure of the environment during flexible, goal-directed behaviour. We highlight that future research should explore the following: (1) Investigate neural responses during spatial navigation via a biophysically plausible framework explained by reinforcement learning models and (2) Observe the interaction between cortical areas and both the dorsal striatum and hippocampus during flexible navigation.
... With respect to the HST, it is unclear whether monkeys use primarily allocentric or egocentric strategies, as the task could potentially be solved using a combination of both. The hippocampus has a well-established selectivity for allocentric over egocentric spatial processing in humans (Bohbot et al. 1998;Spiers, Burgess, Hartley, et al. 2001a;Spiers, Burgess, Maguire, et al. 2001b;Parslow et al. 2004) and in monkeys (Hampton et al. 2004;Banta Lavenex et al. 2006). On the other hand, the PHC seems to be involved in both processes (Bohbot et al. 1998;Weniger and Irle 2006;Weniger et al. 2010). ...
The Hamilton Search Task (HST) is a test of nonnavigational spatial memory that is dependent on the hippocampus. The parahippocampal cortex (PHC) is a major route for spatial information to reach the hippocampus, but the extent to which the PHC and hippocampus function independently of one another in the context of nonnavigational spatial memory is unclear. Here, we tested the hypotheses that (1) bilateral pharmacological inactivation of the PHC would impair HST performance, and (2) that functional disconnection of the PHC and hippocampus by contralateral (crossed) inactivation would likewise impair performance. Transient inactivation of the PHC impaired HST performance most robustly with 30 s intertrial delays, but not when color cues were introduced. Functional disconnection of the PHC and hippocampus, but not separate unilateral inactivation of either region, also selectively impaired long-term spatial memory. These findings indicate a critical role for the PHC and its interactions with the hippocampus in nonnavigational spatial memory.
... Specific hippocampal neurons are highly adapted to process and encode information of the surrounding world [11], making Hp essential for flexible navigation. Existing research shows that the mammals with Hp lesions perform worse in the learning and navigation tasks in the new environment, in which the ability of the optimal routing selection is impaired [12,13]. It indicates that Hp may play an important role in the processing and encoding of the routing-related information. ...
Goal-directed navigation is a crucial behavior for the survival of animals, especially for the birds having extraordinary spatial navigation ability. In the studies of the neural mechanism of the goal-directed behavior, especially involving the information encoding mechanism of the route, the hippocampus (Hp) and nidopallium caudalle (NCL) of the avian brain are the famous regions that play important roles. Therefore, they have been widely concerned and a series of studies surrounding them have increased our understandings of the navigation mechanism of birds in recent years. In this paper, we focus on the studies of the information encoding mechanism of the route in the avian goal-directed behavior. We first summarize and introduce the related studies on the role of the Hp and NCL for goal-directed behavior comprehensively. Furthermore, we review the related cooperative interaction studies about the Hp-NCL local network and other relevant brain regions supporting the goal-directed routing information encoding. Finally, we summarize the current situation and prospect the existing important questions in this field. We hope this paper can spark fresh thinking for the following research on routing information encoding mechanism of birds.
... In this study cognitive functions of the mice was analyzed as described by Tariq et al. (2008), Ahmed et al. (2016), Rutten et al. (2002), Morris (1984), and Abu-Taweel (2018). The experimental procedures were performed for four days (Spiers et al., 2001;Jeltsch et al., 2001). ...
In this study, the role of Lipopolysaccharide (LPS) on the neurochemical disruption and neurobehavioural changes in offspring of mice was analyzed. Totally 30 pregnant mice was selected and divided in to six groups. Apium graveolens was supplemented at various doses to the experimental animals. This experiment was started at the day of pregnancy and was continued up to post-natal day 15. In our experiment three pups from each set of experiment were carefully marked and analyzed its physical, biochemical and behavioral changes. The experimental animals showed decreased body weight, delayed eye opening and delayed hair growth. Also, LPS treated pups showed cliff avoidance and rotating reflexes. Pups exposed to LPS showed heavy learning deficits and memory loss. In the treated pups, decreased level of dopamine, acetylcholinesterase and serotonin in forebrain was observed than celery groups. The present finding showed that the treatment of Celery revealed potent activity on behavior and biochemical disorders. Administration of celery enhanced cognition behavior in experimental animals. Keywords: Neurobehavioral disorders, Behavior, Dopamine, Serotonin, Acetylcholinesterase, Celery
... Developmental amnesia resulting from hypoxic-ischemic insult in the perinatal period is associated with memory deficits that include impairment in incidental recognition memory measured by the object VPC task, as well as spatial relational and episodic memory (for review, see refs. [68][69][70]. Interestingly, as for monkeys, the memory deficits were protracted, becoming apparent only when infants reach school age. ...
Nonhuman primates provide highly valuable animal models that have significantly advanced our understanding of numerous behavioral and biological phenomena in humans. Here, we reviewed a series of developmental neuropsychological studies that informed us on the timing of development of the hippocampus and of hippocampal-dependent cognitive functions in primates. Data indicate that, in primates, the emergence of adult-like proficiency on behavioral tasks sensitive to hippocampal dysfunction is a stepwise process and reflects the gradual maturation of different hippocampal circuits and their connections with other neural structures. Profound and persistent memory loss resulting from insult to the hippocampus in infancy was absent in early infancy but became evident later in childhood and persisted in adulthood, indicating very little sparing or recovery of function. Finally, the early hippocampal insult resulted in both adaptive and maladaptive neuroplasticity: i.e., sparing contextual memory, but affecting working memory processes as well as emotional reactivity and hypothalamic–pituitary–adrenal (HPA) axis functioning. The results provide significant information on the emergence of hippocampal-dependent functions in humans, on the time course of memory impairment in human cases with early hippocampal insult, and on the clinical implication of the hippocampus in developmental neuropsychiatric disorders.
... Concernant le rôle de la formation hippocampique chez l'homme, il existe aujourd'hui un consensus sur son rôle dans la mémoire épisodique (Squire and Morgan 1991, Vargha-Khadem et al. 1997, Eichenbaum 2001. Son rôle dans la navigation a également été démontré chez l'homme (Maguire et al. 1996b, Maguire et al. 1996a, Vargha-Khadem et al. 1997, Maguire et al. 1998Abrahams et al. 1999, Spiers et al. 2001). Les déficits de mémoires spatiale et épisodique sont souvent les premiers symptômes observés chez les patients présentant des lésions des lobes médiaux temporaux dues à la progression de certaines maladies telles que la maladie d'Alzheimer. ...
Les états de veille sont composés d’états cérébraux distincts, corrélés avec différents comportements et caractérisés par des oscillations spécifiques observables dans le potentiel de champ local (Local Field Potential, LFP). Bien que les différents états cérébraux et leur signature dans le LFP aient été caractérisés, les mécanismes cellulaires sous-jacents restent à ce jour peu connus. Des changements des propriétés de neurones uniques seraient corrélés avec, et pourraient participer à la génération de ces changements d’états cérébraux. L’activité coordonnée et synchronisée de neurones facilite certains processus cognitifs tels que la mémoire. L’hippocampe joue un rôle essentiel dans les mémoires spatiale et épisodique, et dans l’hippocampe, CA3 est important pour la formation d’associations facilitant l’encodage rapide de la mémoire. De plus, les informations provenant du cortex entorhinal, du gyrus denté, et de CA3 même sont comparées et intégrées dans CA3 avant d’être transmises à CA1. Lors de périodes de repos, le LFP hippocampique présente une activité large et irrégulière (Large Irregular Activity, LIA), ponctuée par des oscillations plus rapides, les sharp-wave ripples, jouant un rôle dans la consolidation de la mémoire. Lors de périodes exploratoires, le LFP hippocampique oscille aux fréquences theta (6-12 Hz) et gamma (30-100 Hz). Les cellules pyramidales (CP) de CA3 jouent un rôle important dans chacun de ces états ; elles sont nécessaires pour les sharp wave lors de périodes de repos, et les oscillations gamma lors de comportements exploratoires. Dans le but d’étudier les modulations intracellulaires des CP de CA3, nous avons réalisé des enregistrements de patch-clamp en configuration cellule entière chez l’animal éveillé. Nous avons associé ces enregistrements avec des mesures du diamètre pupillaire et de la vitesse de locomotion de l’animal, ainsi qu’avec l’enregistrement de l’activité oscillatoire du LFP dans l’hippocampe. Nos résultats montrent que certaines CP de CA3 sont sensibles à la modulation intracellulaire lors de différents rythmes hippocampiques, et ont tendance à diminuer leur potentiel de membrane moyen, leur excitabilité, leur variance et leur décharge de potentiel d’action lors des oscillations theta par rapport aux périodes de LIA. De futures études permettront de déterminer si ces changements sont dus à des changements d’entrées synaptiques et/ou de neuromodulateurs. Ces modulations pourraient jouer un rôle dans l’émergence des rythmes oscillatoires du LFP, et permettre à CA3 de réaliser différentes fonctions mnésiques à différents moments.
... Although the HF has long been regarded as critical for spatial mapping (e.g., 4,5 ), there is now a large consensus that it is also involved in the temporal organization of memories. Recent findings illustrating that hippocampal and entorhinal cells represent episodic time [9][10][11][12][13][14][15][16] and studies showing specific impairment in the temporal organization of memories in patients with hippocampal damage (e.g., 17 ), provide considerable support for the HF's role in representing both spatial and temporal information. ...
Recent theories of episodic memory (EM) posit that the hippocampus provides a spatiotemporal framework necessary for representing events. If such theories hold true, then does the development of EM in children depend on the ability to first bind spatial and temporal information? And does this ability rely, at least in part, on normal hippocampal function? We investigated the development of EM in children 2–8 years of age (Study 1) and its impairment in Williams Syndrome, a genetic neurodevelopmental disorder characterized by visuospatial deficits and irregular hippocampal function, (Study 2) by implementing a nonverbal object-placement task that dissociates the what, where, and when components of EM. Consistent with the spatiotemporal-framework view of hippocampal EM, our results indicate that the binding of where and when in memory emerges earliest in development, around the age of 3, and is specifically impaired in WS. Space-time binding both preceded and was critical to full EM (what + where + when), and the successful association of objects to spatial locations seemed to mediate this developmental process.
... Recent findings illustrating the properties of hippocampal and entorhinal cells involved in the representation of episodic time (Rubin et al., 2015;Cai, D. J. et al. , 2016;Mau et al., 2018;Eichenbaum, 2014;MacDonald et al., 2011;Tsao et al., 2018), as well as functional imaging studies on patients with hippocampal damages showing specific impairment in the temporal organization of memories (e.g. Konkel, Warren, Duff, Tranel & Cohen, 2008;Spiers, Burgess, Hartley, Vargha-Khadem, O'Keefe J., 2001), provide considerable support for the HF as representing not only spatial but also temporal information. ...
Theories of hippocampal function have proposed that spatiotemporal representations provide a scaffold upon which episodic memories are built. If this is true, does the developmental emergence of adult-like episodic memory in children depend on the successful binding of space with time? To address this question, we report results from two studies aimed at revealing the developmental changes in episodic memory and the specific role of spatiotemporal binding in that process. Study 1 investigated the cognitive mechanisms underlying normal developmental changes in episodic memory across 2-to-8 years of age using an object-hiding game dissociating the content (what) of memories from their spatial (where) and temporal (when) contexts. Study 2 investigated the same episodic memory binding processes in Williams Syndrome patients, who exhibit spatial impairments attributed to their abnormal hippocampal development. Our results indicate that, indeed, the successful binding spatial and temporal memory components emerges first in typical development and is impaired in Williams Syndrome. Furthermore, we found that space-time memory binding not only precedes but also predicts the emergence of episodic memory ability. Finally, an analysis of the separate components of episodic memory suggests that the association of objects to spatial location may play a mediating role in the development of successful episodic memory. Importantly, these effects are not explained by improvements in object or location memory. We interpret these findings to indicate that the ontogenetic origins of episodic memories depend on spatiotemporally organization of memories and that such representations rely, at least in part, on normal hippocampal development and function.
... For cognitive functions, various 5-HT receptor subtypes involve various roles in serotonergic neurotransmission, including the functions related with memory and learning processes (Spiers et al., 2001). In the present study the brain is the most susceptible organ for Hg toxicity by inhibiting the neurotransmitters DA, AchE and 5HT in the forebrain tissues. ...
In the present investigation, the effects of mercuric chloride (HgCl2) on the neurobehavioural and neurochemical disruption in mice offspring was studied. A total of thirty pregnant mice were divided into six groups. Group II and III were received 150 and 300 ppm of curcumin respectively. Group IV was given 10 ppm of HgCl2. Group V and VI were given 10 ppm of HgCl2 with 150 and 300 ppm of curcumin respectively. In this study, treatment started from day one of pregnancy and continued until post-natal day 15 (PD 15). During weaning period, three pups in each experimental group were marked and were subjected to behavioral, physical and biochemical tests. The results revealed decreased body weight, delayed hair growth and eye opening. HgCl2 treated pups taken more time in righting, rotating reflexes to return to normal placement, cliff avoidance compared to that of control group. HgCl2 exposed pups showed memory
and learning deficits. Anxiety behavior in treating pups was increased. Biochemical investigations showed decreased level of dopamine (DA), serotonin (5-HT) and acetylcholinesterase (AChE) in forebrain
of treated pups compared to the control and curcumin groups. The protective effect of curcumin doses were significant compared to HgCl2 group. The results indicated that the administration of curcumin
showed effective activity towards biochemical and behavioral disorders obtained with the HgCl2 treated animals. Overall, the curcumin administration revealed increased cognetion and anxiety behaviors in the treated animals. Conclusively, curcumin has a good benefits for health which can use to avoid toxicants such as Hg and other heavy metals.
... Interestingly, dissociation of increased connectivity in the CN group and decreased connectivity in the AD-spectrum group was especially prominently associated with tau deposition in the hippocampus. The hippocampus plays a critical role in episodic memory and is a key component of the Papez circuit (Aggleton & Brown, 1999;Spiers, Burgess, Hartley, Vargha-Khadem, & O'Keefe, 2001;Squire, 2004;Tsivilis et al., 2008). Neuroinflammation is also associated with normal aging, especially within the hippocampus (Hein & O'Banion, 2009); therefore, compensatory mechanisms associated with the hippocampus may be more significant compared with other brain regions, and when these mechanisms fail, there are likely to be more significant alterations in connectivity. ...
Introduction
Alzheimer's disease (AD) is characterized by accumulation of extracellular amyloid‐β and intracellular tau neurofibrillary tangles. The recent advent of tau positron emission tomography (PET) has enabled in vivo assessment of tau pathology. The aim of this study was to explore whether tau deposition influences the structural connectivity in amyloid‐negative and amyloid‐positive groups, and further explore the difference between the groups.
Methods
We investigated 18 patients with amnestic mild cognitive impairment/mild AD (AD‐spectrum group) and 35 cognitively normal older adults (CN group) using diffusion MRI, amyloid, and tau PET imaging. Diffusion connectometry was performed to identify white matter pathways correlated with each of the six variables of tau deposition in the bilateral hippocampi, temporal lobes, posterior and anterior cingulate cortices, precunei, orbitofrontal lobes, and entire cerebrum.
Results
The CN group showed increased connectivity along with an increased tau deposition in the bilateral hippocampi, temporal lobes, and entire cerebrum, whereas the AD‐spectrum group showed decreased connectivity in the bilateral hippocampi, temporal lobes, anterior and posterior cingulate cortices, precunei, and entire cerebrum.
Conclusion
These findings suggest that tau deposition in the CN group seems to induce a compensatory response against early neuronal injury or chronic inflammation associated with normal aging, whereas the coexistence of amyloid and tau in the AD‐spectrum group seems to outweigh the compensatory response leading to decreased connectivity, suggesting that amyloid plays a crucial role in alternating structural connectivity.
... However, the recent findings about internally generated sequential firing of neuronal ensembles (Pastalkova et al., 2008) and context-specific time cells (MacDonald et al., 2011(MacDonald et al., , 2013 are consistent with the notion of a more active mechanisms in temporal memory, which might, in fact, be very similar to mechanisms in spatial memory (Howard and Eichenbaum, 2015). In humans, it has also been shown that hippocampal damage leads to impairments in both spatial and temporal memory tasks (Spiers et al., 2001;Konkel et al., 2008) and that the hippocampus is active during active retrieval of temporal sequences as well as spatial layouts (Ekstrom et al., 2011), even though dissociable networks for the two retrieval domains were observed outside of the hippocampus. In seeming contrast with our results, one study investigating pattern similarity during retrieval of spatially near versus far intervals and temporally near versus far intervals found an interaction effect in right hippocampus, with increased pattern similarity for spatially far compared to spatially near retrieval trials and the opposite effect for temporally near versus far retrieval trials whereas we find a pattern similarity increase both for spatially close and temporally close pairs of items. ...
The hippocampus has long been implicated in both episodic and spatial memory, however these mnemonic functions have been traditionally investigated in separate research strands. Theoretical accounts and rodent data suggest a common mechanism for spatial and episodic memory in the hippocampus by providing an abstract and flexible representation of the external world. Here, we monitor the de novo formation of such a representation of space and time in humans using fMRI. After learning spatio-temporal trajectories in a large-scale virtual city, subject-specific neural similarity in the hippocampus scaled with the remembered proximity of events in space and time. Crucially, the structure of the entire spatio-temporal network was reflected in neural patterns. Our results provide evidence for a common coding mechanism underlying spatial and temporal aspects of episodic memory in the hippocampus and shed new light on its role in interleaving multiple episodes in a neural event map of memory space.
DOI: http://dx.doi.org/10.7554/eLife.16534.001
... The unsuccessful trials were noted in the percentage of the failure in each day of the swimming of the pups. In addition, the hippocampal-dependent spatial reference memory was noted from the pups by following the methodology of (Jeltsch et al., 2001;Spiers et al., 2001). ...
Cardamom is a strong antioxidant plant, so it is called the queen of spices. In the present study, we explored the potentials of cardamom on developmental, learning ability and biochemical parameters of mice offspring. Thirty pregnant mice were allocated to three groups of ten animals in each. Groups Π and Sh(cyrillic) received pilsbury's Diet containing 10 and 20% of cardamom (w/w) respectively, whereas Group I used as control. Cardomom was administered from the first day of pregnancy and was continued until post-natal day 15 (PD 15) and thereafter the mothers were switched to plain pilsbury's Diet. During the weaning period, three pups in each litter were color marked from the others, and were subjected to various tests (Physical assessment such body weight and eye opening and hair appearance; the neuromaturation of reflexes like righting, rotating, and cliff avoidance reflexes; learning ability and memory retention; estimation of monoamines neurotransmitters like dopamine and serotonin, non-enzymatic oxidative stress such as TBARS and GSH in forebrain at different ages of pups). The results indicated that the body weight gain was declining significantly. Hair appearance and eyes opening were delayed significantly. Righting, rotating, and cliff avoidance reflexes were delayed in treated animals. Exposure to cardamom led to enhance learning and memory retention as compared to control. Monoamines (DA, 5-HT) and GSH were elevated, whereas TBARS was inhibited significantly. In conclusion, perinatal cardamom exposure enhanced learning and memory as compared to control. Cardamom and its benefit compounds were transported via placenta or/and milk during lactation. Cardamom needs more researches to investigate its benefits on other kinds of behavior.
... Although Mac-Donald and colleagues [23,61] have suggested that the hippocampus plays a more prominent role in retrospective than in prospective judgments, there are nonetheless conditions under which the hippocampus is critical for prospective time judgments (see Section 1, which discusses prospective time estimation tasks). Allowing for greater neuroanatomical specificity than the foregoing studies, two single-case studies of patients with damage restricted to the hippocampus have demonstrated impaired temporal order in the context of normal recognition memory performance [32,33]. For example, Mayes et al. [33] showed a deficit for temporal order in a hippocampal-only patient across a range of tasks. ...
Time and space are two critical elements of episodic memory that are supported by the hippocampus. Yet, until recently, there has been much greater focus on the involvement of this structure in spatial than in temporal features of memory. Here we highlight evidence from neuropsychological studies of patients with medial temporal lobe lesions, which have provided evidence that the hippocampus is critical for multiple facets of time, even in tasks that are not typically considered episodic. These studies show that the hippocampus supports memory for first, event duration, second, temporal order, and third, temporally discontiguous experiences. Overall, these findings align with theoretical models suggesting that the hippocampus codes for the temporal context of unfolding events.
... Considering that goal-directed movements with or without the body as the coordinate reference point is the key dimension along which allocentric and egocentric responses differ, this may explain overall increased activity in the extrastriate component cluster in our language task. Studies also highlight the importance of the hippocampus and parahippocampal areas in storing, recalling, and processing spatial information based on landmarks, cardinal directions, and environmental cuesin other words, allocentrically coded information (Aguirre & D'Esposito, 1999;Galati et al., 2000;Spiers et al., 2001;Zaehle et al., 2007). ...
The hippocampus (HPC) and retrosplenial cortex (RSC) are key components of the brain's memory and navigation systems. Lesions of either region produce profound deficits in spatial cognition and HPC neurons exhibit well‐known spatial firing patterns (place fields). Recent studies have also identified an array of navigation‐related firing patterns in the RSC. However, there has been little work comparing the response properties and information coding mechanisms of these two brain regions. In the present study, we examined the firing patterns of HPC and RSC neurons in two tasks which are commonly used to study spatial cognition in rodents, open field foraging with an environmental context manipulation and continuous T‐maze alternation. We found striking similarities in the kinds of spatial and contextual information encoded by these two brain regions. Neurons in both regions carried information about the rat's current spatial location, trajectories and goal locations, and both regions reliably differentiated the contexts. However, we also found several key differences. For example, information about head direction was a prominent component of RSC representations but was only weakly encoded in the HPC. The two regions also used different coding schemes, even when they encoded the same kind of information. As expected, the HPC employed a sparse coding scheme characterized by compact, high contrast place fields, and information about spatial location was the dominant component of HPC representations. RSC firing patterns were more consistent with a distributed coding scheme. Instead of compact place fields, RSC neurons exhibited broad, but reliable, spatial and directional tuning, and they typically carried information about multiple navigational variables. The observed similarities highlight the closely related functions of the HPC and RSC, whereas the differences in information types and coding schemes suggest that these two regions likely make somewhat different contributions to spatial cognition.
Decades of studies robustly support a critical role for the hippocampus in spatial memory across a wide range of species. Hippocampal damage produces clear and consistent deficits in allocentric spatial memory that requires navigating through space in rodents, non‐human primates, and humans. By contrast, damage to the hippocampus spares performance in most non‐navigational spatial memory tasks—which can typically be resolved using egocentric cues. We previously found that transient inactivation of the hippocampus impairs performance in the Hamilton Search Task (HST), a self‐ordered non‐navigational spatial search task. A key question, however, still needs to be addressed. Acute, reversible inactivation of the hippocampus may have resulted in an impairment in the HST because this approach does not allow for neuroplastic compensation, may prevent the development of an alternative learning strategy, and/or may produce network‐based effects that disrupt performance. We compared learning and performance on the HST in male rhesus macaques (six unoperated control animals and six animals that underwent excitotoxic lesions of the hippocampus). We found a significant impairment in animals with hippocampal lesions. While control animals improved in performance over the course of 45 days of training, performance in animals with hippocampal lesions remained at chance levels. The HST thus represents a sensitive assay for probing the integrity of the hippocampus in non‐human primates. These data provide evidence demonstrating that the hippocampus is critical for this type of non‐navigational spatial memory, and help to reconcile the many null findings previously reported.
Sex differences in navigation have been a topic of investigation for decades and has been subjected to various contradictory findings and debates. The aim of this work was to compare the spatial memory of men and women tested in various different types of spatial tasks, while controlling for navigation strategies and aging. It is generally thought that men outperform women in navigation and that women have higher scores on object location tasks. However, many studies fail to control for different factors that may bias one sex or the other. We aggregated the data of 465 participants (349 young adults, 127 older adults) who took part in various studies conducted in our laboratory, which include both published and original unpublished data, in order to investigate sex differences. In these studies, we used a number of different paradigms: virtual radial arm mazes, a virtual wayfinding task, an object location task, a virtual Morris Water Maze, and the invisible sensor task which is a real-life model of the Morris Water Maze. While our results may seem discordant at first glance, they demonstrate that several factors can impact the performance of men and women on spatial tasks, including spontaneous navigation strategies, environmental characteristics, and age. We replicated findings showing that women favor proximal landmarks compared to men who favor distal landmarks, women have better memory than men for the position of objects in the absence of reference frames, but they will have poorer scores when navigation requires specific angles, distances and polar coordinates. Moreover, we found that in aging, women who avoid the use of landmarks when navigating a radial maze show stronger reliance on these non-spatial strategies than men. On the other hand, women who rely on landmarks, do so to the same extent as men. Our findings highlight the need to carefully take into consideration these factors in order to produce a more harmonious understanding of sex differences in navigation. Finally, the interaction between spontaneous navigation strategies, sex, and age is discussed in terms of its implications for risk of Alzheimer’s disease.
Despite its prominence in learning and memory, hippocampal influence in early auditory processing centers remains unknown. Here, we examined how hippocampal activity modulates sound-evoked responses in the auditory midbrain and thalamus using optogenetics and functional MRI (fMRI) in rodents. Ventral hippocampus (vHP) excitatory neuron stimulation at 5 Hz evoked robust hippocampal activity that propagates to the primary auditory cortex. We then tested 5Hz vHP stimulation paired with either natural vocalizations or artificial/noise acoustic stimuli. vHP stimulation enhanced auditory responses to vocalizations (with a negative or positive valence) in the inferior colliculus, medial geniculate body, and auditory cortex, but not to their temporally reversed counterparts (artificial sounds) or broadband noise. Meanwhile, pharmacological vHP inactivation diminished response selectivity to vocalizations. These results directly reveal the large-scale hippocampal participation in natural sound processing at early centers of the ascending auditory pathway. They expand our present understanding of hippocampus in global auditory networks.
Inuit communities in Northern Quebec (Canada) are exposed to environmental contaminants, particularly to mercury, lead and polychlorinated biphenyls (PCBs). Previous studies reported adverse associations between these neurotoxicants and memory performance. Here we aimed to determine the associations of pre- and postnatal exposures to mercury, lead and PCB-153 on spatial navigation memory in 212 Inuit adolescents (mean age = 18.5 years) using a computer task which requires learning the location of a hidden platform based on allocentric spatial representation. Contaminant concentrations were measured in cord blood at birth and blood samples at 11 years of age and at time of testing. Multivariate regression models showed that adolescent mercury and prenatal PCB-153 exposures were associated with poorer spatial learning, whereas current exposure to PCB-153 was associated with altered spatial memory retrieval at the probe test trial. These findings suggest that contaminants might be linked to different aspects of spatial navigation processing at different stages.
Animals and humans are remarkable in their ability to flexibly adapt to changes in their surroundings. Navigational flexibility may take many forms and in this thesis we investigate its neural and behavioral underpinnings using a variety of methods and tasks tailored to each specific research aim. These methods include functional resonance magnetic imaging (fMRI), freely moving virtual reality, desktop virtual reality, large-scale online testing, and computational modelling. First, we reanalysed previously collected rodent data in the lab to better under- stand behavioural bias that may occur during goal-directed navigation tasks. Based on finding some biases we designed a new approach of simulating results on maze configurations prior to data collection to select the ideal mazes for our task. In a parallel line of methods development, we designed a freely moving navigation task using large-scale wireless virtual reality in a 10x10 space. We compared human behaviour to that of a select number of reinforcement learning agents to investigate the feasibility of computational modelling approaches to freely moving behaviour. Second, we further developed our new approach of simulating results on maze configuration to design a novel spatial navigation task used in a parallel experiment in both rats and humans. We report the human findings using desktop virtual reality and fMRI. We identified a network of regions including hippocampal, caudate nu- cleus, and lateral orbitofrontal cortex involvement in learning hidden goal locations. We also identified a positive correlation between Euclidean goal distance and brain activity in the caudate nucleus during ongoing navigation. Third, we developed a large online testing paradigm to investigate the role of home environment on wayfinding ability. We extended previous reports that street network complexity is beneficial in improving wayfinding ability as measured using a previously reported virtual navigation game, Sea Hero Quest, as well as in a novel virtual navigation game, City Hero Quest. We also report results of a navigational strategies questionnaire that highlights differences of growing up inside and outside cities in the United States and how this relates to wayfinding ability. Fourth, we investigate route planning in a group of expert navigators, licensed London taxi drivers. We designed a novel mental route planning task, probing 120 different routes throughout the extensive street network of London. We find hip- pocampal and retrosplenial involvement in route planning. We also identify the frontopolar cortex as one of several brain regions parametrically modulated by plan- ning demand. Lastly, I summarize the findings from these studies and how they all come to provide different insights into our remarkable ability to flexibly adapt to naviga- tional challenges in our environment.
Licensed London taxi drivers have been found to show changes in the gray matter density of their hippocampus over the course of training and decades of navigation in London (UK). This has been linked to their learning and using of the “Knowledge of London,” the names and layout of over 26,000 streets and thousands of points of interest in London. Here we review past behavioral and neuroimaging studies of London taxi drivers, covering the structural differences in hippocampal gray matter density and brain dynamics associated with navigating London. We examine the process by which they learn the layout of London, detailing the key learning steps: systematic study of maps, travel on selected overlapping routes, the mental visualization of places and the optimal use of subgoals. Our analysis provides the first map of the street network covered by the routes used to learn the network, allowing insight into where there are gaps in this network. The methods described could be widely applied to aid spatial learning in the general population and may provide insights for artificial intelligence systems to efficiently learn new environments.
Licenced London taxi drivers have been found to show changes in the grey matter density of their hippocampus over the course of training and decades of navigation in London (UK). This has been linked to their learning and using of the Knowledge of London, the names and layout of over 26,000 streets and thousands of points of interest in London. Here we examined the process of how this knowledge is acquired and we detail key steps that include: systematic study of maps, travel on selected overlapping routes, the mental visualisation of places and the optimal use of subgoals. We provide the first map of the street network covered by the routes used to learn, allowing insight into where gaps in the network exist. The methods could be widely applied to aid spatial learning in the general population and may provide insights for artificial intelligence (AI) systems to efficiently learn new environments.
We generate mental representations of space to facilitate our ability to remember things and navigate our environment. Many studies implicitly assume that these representations simply reflect the environments that they represent without considering other factors that influence the extent to which this is the case. Here, we bring together findings from cognitive psychology, environmental psychology, geography, urban planning, and neuroscience to discuss how internalizing the environment involves a complex interplay between bottom-up and top-down mental processes and depends on key characteristics of the physical environment itself. We describe how mental space is structured, the ways in which mental and physical space converge and diverge, and the disparate but complementary techniques used to assess these relationships. Finally, we contextualize this knowledge in the clinical populations affected by acquired and developmental topographical disorientation, exploring mechanisms that cause these patients to get lost in familiar surroundings.
Epilepsy is considered a major serious chronic neurological disorder, characterized by recurrent seizures. It is usually associated with a history of a lesion in the nervous system. Irregular activation of inflammatory molecules in the injured tissue is an important factor in the development of epilepsy. It is unclear how the imbalanced regulation of inflammatory mediators contributes to epilepsy. A recent research goal is to identify interconnected inflammation pathways which may be involved in the development of epilepsy. The clinical use of available antiepileptic drugs is often restricted by their limitations, incidence of several side effects, and drug interactions. So development of new drugs, which modulate epilepsy through novel mechanisms, is necessary. Alternative therapies and diet have recently reported positive treatment outcomes in epilepsy. Vitamin D (Vit D) has shown prophylactic and therapeutic potential in different neurological disorders. So, the aim of current study was to review the associations between different brain inflammatory mediators and epileptogenesis, to strengthen the idea that targeting inflammatory pathway may be an effective therapeutic strategy to prevent or treat epilepsy. In addition, neuroprotective effects and mechanisms of Vit D in clinical and preclinical studies of epilepsy were reviewed.
The ability to adapt to new situations involves behavioral changes expressed either from an innate repertoire, or by acquiring experience through memory consolidation mechanisms, by far a much richer and flexible source of adaptation. Memory formation consists of two interrelated processes that take place at different spatial and temporal scales, Synaptic Consolidation, local plastic changes in the recruited neurons, and Systems Consolidation, a process of gradual reorganization of the explicit/declarative memory trace between hippocampus and the neocortex. In this review, we summarize some converging experimental results from our lab that support a normal temporal framework of memory systems consolidation as measured both from the anatomical and the psychological points of view, and propose a hypothetical model that explains these findings while predicting other phenomena. Then, the same experimental design was repeated interposing additional tasks between the training and the remote test to verify for any interference: we found that (a) when the animals were subject to a succession of new learnings, systems consolidation was accelerated, with the disengagement of the hippocampus taking place before the natural time point of this functional switch, but (b) when a few reactivation sessions reexposed the animal to the training context without the shock, systems consolidation was delayed, with the hippocampus prolonging its involvement in retrieval. We hypothesize that new learning recruits from a fixed number of plastic synapses in the CA1 area to store the engram index, while reconsolidation lead to a different outcome, in which additional synapses are made available. The first situation implies the need of a reset mechanism in order to free synapses needed for further learning, and explains the acceleration observed under intense learning activity, while the delay might be explained by a different process, able to generate extra free synapses: depending on the cognitive demands, it deals either with a fixed or a variable pool of available synapses. The Synaptic Occupancy/Reset Theory (SORT) emerged as an explanation for the temporal flexibility of systems consolidation, to encompass the two different dynamics of explicit memories, as well as to bridge both synaptic and systems consolidation in one single mechanism.
Across three different domains, there are similar sex differences in how men and women process information. There tends to be a male advantage in attending to and remembering the gist (essential central information of a scene or situation), but a female advantage in attending to and remembering the details (non-essential peripheral information of a scene or situation). This is seen in emotional memory, where emotion enhances gist memory more for males than for females, but enhances detail memory more for females than for males. It also occurs in spatial memory, where men tend to notice and remember the gist of where they or objects are in space, allowing them to more flexibly manipulate themselves or objects within that space, whereas women tend to recall the details of the space around them, allowing them to accurately remember the locations of objects. Finally, such sex differences have also been noted in perception of stimuli such that men attend to global aspects of stimuli (such as a large letter A) more than women, whereas women attend more to the local aspects (such as the many smaller letter Ts making up the A). We review the parallel sex differences seen across these domains in this paper and how they relate to the different brain systems involved in each of these task domains. In addition, we discuss how sex differences in evolutionary pressures and in the locus coeruleus and norepinephrine system may account for why parallel sex differences occur across these different task domains.
The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred.
SIGNIFICANCE STATEMENT Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory.
People acquire spatial knowledge by physically experiencing the environment through locomotion. Spatial knowledge generally emerges from the interactions between the specific types of sensory data and the cognitive strategies involved in locomotion. This chapter reviews the fundamental concepts and evidences of spatial cognition. First, the interplay between visual data and mobility is addressed. The importance of landmarks and visual cues is highlighted for implementing both simple and complex navigation strategies such as path integration (PI), landmark-based, and geometry-based, which are the main cognitive mechanisms for spatial learning. Some neural evidences of spatial cognition are given to underline the brain mechanisms involved in cognitive mapping. A review of relevant literature models on cognitive mapping is also presented to better understand how spatial representations are formed at the level of the brain. The chapter provides some insights on how to adapt all these concepts for mobility and spatial knowledge assistance of people with visual impairments.
During the past 100 years clinical studies of amnesia have linked memory impairment to damage of the hippocampus. Yet the damage in these cases has not usually been confined to the hippocampus, and the status of memory functions has often been based on incomplete neuropsychological information. Thus, the human cases have until now left some uncertainty as to whether lesions limited to the hippocampus are sufficient to cause amnesia. Here we report a case of amnesia in a patient (R.B.) who developed memory impairment following an ischemic episode. During the 5 years until his death, R.B. exhibited marked anterograde amnesia, little if any retrograde amnesia, and showed no signs of cognitive impairment other than memory. Thorough histological examination revealed a circumscribed bilateral lesion involving the entire CA1 field of the hippocampus. Minor pathology was found elsewhere in the brain (e.g., left globus pallidus, right postcentral gyrus, left internal capsule), but the only damage that could be reasonably associated with the memory defect was the lesion in the hippocampus. To our knowledge, this is the first reported case of amnesia following a lesion limited to the hippocampus in which extensive neuropsychological and neuropathological analyses have been carried out.
We report the performance on recognition memory tests of Jon, who, despite amnesia from early childhood, has developed normal levels of performance on tests of intelligence, language, and general knowledge. Despite impaired recall, he performed within the normal range on each of six recognition tests, but he appears to lack the recollective phenomenological experience normally associated with episodic memory. His recall of previously unfamiliar newsreel event was impaired, but gained substantially from repetition over a 2-day period. Our results are consistent with the hypothesis that the recollective process of episodic memory is not necessary either for recognition or for the acquisition of semantic knowledge.
Virtual reality (VR) and event-related functional magnetic resonance imaging were used to study memory for the spatial context of controlled but lifelike events. Subjects received a set of objects from two different people in two different places within a VR environment. Memory for the objects, and for where and from whom they were received was tested by putting the subject back into a place in the company of a person and giving a paired forced choice of objects. In four conditions objects had to be chosen according to different criteria: which was received in that place, which was received from that person, which object was recognized, and which object was widest. Event-related functional magnetic resonance imaging was performed during testing to identify areas involved in retrieval of the spatial context of an event. A network of areas was identified consisting of a temporoparietal pathway running between the precuneus and parahippocampi via retrosplenial cortex and the parieto-occipital sulcus, left hippocampus, bilateral posterior parietal, dorsolateral, ventrolateral and anterior prefrontal cortices, and the anterior cingulate. Of these areas the parahippocampal, right posterior parietal, and posteriodorsal medial parietal areas were specifically involved in retrieval of spatial context compared to retrieval of nonspatial context. The posterior activations are consistent with a model of long-term storage of allocentric representations in medial temporal regions with translation to body-centered and head-centered representations computed in right posterior parietal cortex and buffered in the temporoparietal pathway so as to provide an imageable representation in the precuneus. Prefrontal activations are consistent with strategic retrieval processes, including those required to overcome the interference between the highly similar events.
The neural basis of navigation by humans was investigated with functional neuroimaging of brain activity during navigation
in a familiar, yet complex virtual reality town. Activation of the right hippocampus was strongly associated with knowing
accurately where places were located and navigating accurately between them. Getting to those places quickly was strongly
associated with activation of the right caudate nucleus. These two right-side brain structures function in the context of
associated activity in right inferior parietal and bilateral medial parietal regions that support egocentric movement through
the virtual town, and activity in other left-side regions (hippocampus, frontal cortex) probably involved in nonspatial aspects
of navigation. These findings outline a network of brain areas that support navigation in humans and link the functions of
these regions to physiological observations in other mammals.
The involvement of the medial temporal-lobe region in allocentric mapping of the environment has been observed in human lesion and functional imaging work. Cognitive models of environmental learning ascribe a key role to salient landmarks in representing large-scale space. In the present experiments we examined the neural substrates of the topographical memory acquisition process when environmental landmarks were more specifically identifiable. Using positron emission tomography (PET), we measured regional cerebral blood flow changes while normal subjects explored and learned in a virtual reality environment. One experiment involved an environment containing salient objects and textures that could be used to discriminate different rooms. Another experiment involved a plain empty environment in which rooms were distinguishable only by their shape. Learning in both cases activated a network of bilateral occipital, medial parietal, and occipitotemporal regions. The presence of salient objects and textures in an environment additionally resulted in increased activity in the right parahippocampal gyrus. This region was not activated during exploration of the empty environment. These findings suggest that encoding of salient objects into a representation of large-scale space is a critical factor in instigating parahippocampal involvement in topographical memory formation in humans and accords with previous studies implicating parahippocampal areas in the encoding of object location.
As we move around in our environment, and interact with it, many of the most important problems we face involve the processing of spatial information. We have to be able to navigate by perceiving and remembering the locations and orientations of the objects around us relative to ourself; we have to sense and act upon these objects; and we need to move through space to position ourselves in favourable locations or to avoid dangerous ones. While this appears so simple that we don't even think about it, the difficulty of solving these problems has been shown in the repeated failure of artificial systems to perform these kinds of tasks efficiently. In contrast, humans and other animals routinely overcome these problems every single day. This book examines some of the neural substrates and mechanisms that support these remarkable abilities. The hippocampus and the parietal cortex have been implicated in various core spatial behaviours, such as the ability to localise an object and navigate to it. Damage to these areas in humans and animals leads to impairment of these spatial functions. This collection of papers, written by internationally recognized experts in the field, reviews the evidence that each area is involved in spatial cognition, examines the mechanisms underlying the generation of spatial behaviours, and considers the relative roles of the parietal and hippocampal areas, including how each interacts with the other. The papers integrate a wide range of theoretical and experimental approaches, and touch on broader issues relating to memory and imagery. As such, this book represents the state of the art of current research into the neural basis of spatial cognition. It should be of interest to anyone - researchers or graduate students - working in the areas of cognitive neuroscience, neuroanatomy, neuropsychology, and cognition generally.
During the past 100 years clinical studies of amnesia have linked memory impairment to damage of the hippocampus. Yet the damage in these cases has not usually been confined to the hippocampus, and the status of memory functions has often been based on incomplete neuropsychological information. Thus, the human cases have until now left some uncertainty as to whether lesions limited to the hippocampus are sufficient to cause amnesia. Here we report a case of amnesia in a patient (R.B.) who developed memory impairment following an ischemic episode. During the 5 years until his death, R.B. exhibited marked anterograde amnesia, little if any retrograde amnesia, and showed no signs of cognitive impairment other than memory. Thorough histological examination revealed a circumscribed bilateral lesion involving the entire CA1 field of the hippocampus. Minor pathology was found elsewhere in the brain (e.g., left globus pallidus, right postcentral gyrus, left internal capsule), but the only damage that could be reasonably associated with the memory defect was the lesion in the hippocampus. To our knowledge, this is the first reported case of amnesia following a lesion limited to the hippocampus in which extensive neuropsychological and neuropathological analyses have been carried out.
The hippocampus has been proposed as the site of neural representation of large-scale environmental space, based upon the
identification of place cells (neurons with receptive fields for current position in the environment) within the rat hippocampus
and the demonstration that hippocampal lesions impair place learning in therat. The inability to identify place cells within
the monkey hippocampus and the observation that unilateral hippocampal lesions do not selectively impair topographic behavior
in humans suggest that alternate regions may subserve this function in man. To examine the contribution of the hippocampus
and adjacent medial-temporal lobe structures to topographic learning in the human, a ‘virtual’ maze was used as a task environment
during functional magnetic resonance imaging studies. During the learning and recall of topographic information, medial-temporal
activity was confined to the para- hippocampal gyri. This activity accords well with the lesion site known to produce topographical
disorientation in humans. Activity was also observed in cortical areas known to project to the parahippocampus and previously
proposed to contribute to a network subserving spatially guided behavior.
We report a single-case study of a patient who suddenly lost her ability to orient herself in her neighbourhood. On formal testing she demonstrated remarkably selective deficits in episodic and semantic memory of topographical items and rouse. Her general intellectual abilities were unaffected as were basic perceptual processes and episodic and semantic memory other than topography. We interpret her deficit as a further example of category-specific processing impairment affecting knowledge acquired through selective channels-in this case visuo-locomotor information.
The importance of the hippocampal formation of the brain for allocentric spatial mapping of the environment has been suggested by animal lesion and electrophysiological work. Here we describe a positron emission tomography (PET) study designed to investigate the regional cerebral blood flow changes associated with topographical memory formation in humans, i.e. the formation of representations of large-scale environments necessary for way-finding. Topographical learning of an urban environment from viewing of film footage depicting navigation was associated with activation of the right parahippocampal gyrus and hippocampus, with activation also of the left parahippocampal gyrus. In addition, there was activity in the pretuneus. In contrast, the encoding of non-navigation episodic memory in a similar realworld context was not associated with activity in the hippocampal formation. Our results shed light on the neural basis of the human representation of large-scale space pinpointing a particular role for the human hippocampal formation in learning to find one's way.
Positron emission tomography was used to investigate the functional anatomy of mental simulation of routes (MSR) in five normal volunteers. Normalized regional cerebral blood flow was measured while subjects mentally navigated between landmarks of a route which had been previously learned by actual navigation. This task was contrasted with both static visual imagery of landmarks (VIL) and silent Rest. MSR appears to be subserved by two distinct networks: a non-specific memory network including the posterior and middle parts of the hippocampal regions, the dorsolateral prefrontal cortex and the posterior cingulum, and a specific mental navigation network, comprising the left precuneus, insula and medial part of the hippocampal regions.
Global anterograde amnesia is described in three patients with brain injuries that occurred in one case at birth, in another
by age 4, and in the third at age 9. Magnetic resonance techniques revealed bilateral hippocampal pathology in all three cases.
Remarkably, despite their pronounced amnesia for the episodes of everyday life, all three patients attended mainstream schools
and attained levels of speech and language competence, literacy, and factual knowledge that are within the low average to
average range. The findings provide support for the view that the episodic and semantic components of cognitive memory are
partly dissociable, with only the episodic component being fully dependent on the hippocampus.
Functional imaging to date has examined the neural basis of knowledge of spatial layouts of large-scale environments typically in the context of episodic memory with specific spatiotemporal references. Much human behavior, however, takes place in very familiar environments in which knowledge of spatial layouts has entered the domain of general facts often referred to as semantic memory. In this study, positron emission tomography (PET) was used to examine the neural substrates of topographical memory retrieval in licensed London taxi drivers of many years experience while they recalled complex routes around the city. Compared with baseline and other nontopographical memory tasks, this resulted in activation of a network of brain regions, including the right hippocampus. Recall of famous landmarks for which subjects had no knowledge of their location within a spatial framework activated similar regions, except for the right hippocampus. This suggests that the hippocampus is involved in the processing of spatial layouts established over long time courses. The involvement of similar brain areas in routes and landmarks memory indicates that the topographical memory system may be primed to respond to any relevant topographical stimulation; however, the right hippocampus is recruited specifically for navigation in large-scale spatial environments. In contrast, nontopographical semantic memory retrieval involved the left inferior frontal gyrus, with no change in activity in medial temporal regions.
Studies of patients with focal brain damage suggest that topographical representation is subserved by dissociable neural subcomponents. This article offers a condensed review of the literature of "topographical disorientation" and describes several functional MRI studies designed to test hypotheses generated by that review. Three hypotheses are considered: (i) The parahippocampal cortex is critically involved in the acquisition of exocentric spatial information in humans; (ii) separable, posterior, dorsal, and ventral cortical regions subserve the perception and long term representation of position and identity, respectively, of landmarks; and (iii) there is a distinct area of the ventral occipitotemporal cortex that responds maximally to building stimuli and may play a role in the perception of salient landmarks. We conclude with a discussion of the inferential limitations of neuroimaging and lesion studies. It is proposed that combining these two approaches allows for inferences regarding the computational involvement of a neuroanatomical substrate in a given cognitive process although neither method can strictly support this conclusion alone.
In all cognitive tasks, general task-related processes operate
throughout a given task on all items, whereas specific item-related
processes operate differentially on individual items. In typical
functional neuroimaging experiments, these two sets of processes have
usually been confounded. Herein we report a combined positron emission
tomography and event-related potential (ERP) experiment that was
designed to distinguish between neural correlates of task-related and
item-related processes of memory retrieval. Two retrieval tasks,
episodic and semantic, were crossed with episodic (old/new) and
semantic (living/nonliving) properties of individual items to yield
evidence of regional brain activity associated with task-related
processes, item-related processes, and their interaction. The results
showed that episodic retrieval task was associated with increased blood
flow in right prefrontal and posterior cingulate cortex, as well as
with a sustained right-frontopolar-positive ERP, but that the semantic
retrieval task was associated with left frontal and temporal lobe
activity. Retrieval of old items was associated with increased blood
flow in the left medial temporal lobe and with a brief late positive
ERP component. The results provide converging hemodynamic and
electrophysiological evidence for the distinction of task- and
item-related processes, show that they map onto spatially and
temporally distinct patterns of brain activity, and clarify the
hemispheric encoding/retrieval asymmetry (HERA) model of prefrontal
encoding and retrieval asymmetry.
Over the last century, several dozen case reports have presented 'topographically disoriented' patients who, in some cases, appear to have selectively lost their ability to find their way within large-scale, locomotor environments. A review is offered here that has as its aim the creation of a taxonomy that accurately reflects the behavioural impairments and neuroanatomical findings of this literature. This effort is guided by an appreciation of the models of normative way-finding offered by environmental psychology and recent neuroscience research. It is proposed that several varieties of topographical disorientation exist, resulting from damage to distinct neuroanatomical areas. The particular pattern of impairments that patients evidence is argued to be consonant with the known functions of these cortical regions and with recent neuroimaging results. The conflicting claims of previous reviews of this area are also considered and addressed.
Studies on the amnesic patient H.M. began the modern era of the cognitive neuroscience of memory. These studies, and other case studies, showed that damage limited to the hippocampal region results in an impairment that is selective to memory and spares other perceptual, motor, emotional, or cognitive functions. Furthermore, the amnesic deficit is selective to the permanent establishment of new declarative memories. Thus H.M. and other patients with hippocampal damage have intact short-term and working memory, and can form long-term memories that do not rely on remembering specific past events or on the flexible use of memories to solve new problems. These and other characteristics of amnesia following hippocampal damage indicate that the hippocampal memory system is essential to relational memory, the ability to associate multiple events with one other and with their spatial and temporal context, and the ability to integrate many memories into a network of knowledge.
We recently reported on three young patients with severe impairments of episodic memory resulting from brain injury sustained early in life. These findings have led us to hypothesize that such impairments might be a previously unrecognized consequence of perinatal hypoxic–ischaemic injury. Neuropsychological and quantitative magnetic resonance investigations were carried out on five young patients, all of whom had suffered hypoxic–ischaemic episodes at or shortly after birth. All five patients showed severe impairments of episodic memory (memory for events), with relative preservation of semantic memory (memory for facts). However, none had any of the major neurological deficits that are typically associated with hypoxic–ischaemic injury, and all attended mainstream schools. Quantitative magnetic resonance investigations revealed severe bilateral hippocampal atrophy in all cases. As a group, the patients also showed bilateral reductions in grey matter in the regions of the putamen and the ventral part of the thalamus. On the basis of their clinical histories and the pattern of magnetic resonance findings, we attribute the patients' pathology and associated memory impairments primarily to hypoxic–ischaemic episodes sustained very early in life. We suggest that the degree of hypoxia–ischaemia was sufficient to produce selective damage to particularly vulnerable regions of the brain, notably the hippocampi, but was not sufficient to result in the more severe neurological and cognitive deficits that can follow hypoxic–ischaemic injury. The impairments in episodic memory may be difficult to recognize, particularly in early childhood, but this developmental amnesia can have debilitating consequences, both at home and at school, and may preclude independent life in adulthood.
The present study compared the recognition memory deficit in different groups of amnesics using scores from a standard test. The data, taken from a literature search, came from 33 studies reporting the performance of amnesic subjects on the recognition memory test (RMT) [77]. A total of 112 amnesic subjects were grouped according to their pathology. In addition, the analysis included subjects with schizophrenia, amygdala damage, or frontal lobe damage. Of these three nonamnesic groups, only the frontal lobe subjects were impaired on both RMT subtests, while the schizophrenics showed a disproportionate impairment for the recognition of faces. The amygdala subjects were also poor at face recognition. Among the amnesic groups, those subjects likely to have multiple sites of pathology (e.g. Korsakoff amnesics, post-encephalitics) were found to be the most impaired on the RMT. In contrast, those amnesics with more focal, limbic lesions in the hippocampus, fornix, or mamillary body region showed much milder deficits on the RMT task, some performing at normal levels. Despite their apparent sparing of recognition, the overall severity of amnesia in those subjects with limbic lesions appeared comparable to that in the remaining amnesics. These findings indicate that deficits on both subtests of the RMT are a frequent but not inevitable component of anterograde amnesia. They also point to a distinct subgroup of amnesias associated with selective damage in the hippocampus or its diencephalic targets, in which there is a relative sparing of recognition under certain test conditions.
Seventy-nine patients with different cerebral lesions were trained on a visually- guided stylus maze. The main findings were: (1) bilateral hippocampal lesions produced the most severe impairment, with one patient showing no progress in 215 trials; (2) right temporal lobectomy produced a significant deficit, particularly when the underlying hippocampus was radically excised, whereas patients with left temporal-lobe lesions of equal extent, or with small parietal-lobe lesions of either hemisphere, obtained normal scores; (3) larger lesions of frontal or right posterior cortex severely impaired maze learning, suggesting that size as well as locus of cortical lesion may be a factor in maze-performance; (4) only frontal-lobe lesions affected the ability to follow test instructions.
The relationship between memory performance in everyday life and performance on laboratory tests was investigated in a group of subjects with normal memory and two groups of severely head-injured subjects differing in time since injury (several months vs several years). Everyday memory was assessed using questionnaires and checklists completed by each subject and independently by a relative who was in daily contact with him. Overall, a high degree of consistency was found among these measures, though the lower consistency of the subjects' questionnaire illustrated the problems of validity with self-assessment. The relatives' questionnaire correlated with test performance for normal subjects and for the long-term head-injured group but not for the recently head-injured subjects who had not yet reached a stable state. The highest correlations were with prose recall and paired-associate learning. The absence of correlations with visual memory tests may have been due to low salience of visual errors in everyday life.
Men with right, left and bilateral cerebral lesions were required to make right/left judgements under two experimental conditions, in one of which a mental re-orientation of the stimulus was presumed to be required. Schematic drawings of a man were exposed in either an upright or inverted position and, on each trial, one of the hands was marked. The subject's task was to say “right” or “left” depending on the hand marked. The right posterior group made fewer errors than the left posterior group under the upright condition but significantly more under the inverted condition. This result is attributed to their failure to perform an appropriate mental rotation of the inverted stimuli.
We describe a patient who developed topographical memory loss after a closed head injury. His symptoms and the psychological test results indicate a selective deficit of topographical memory, his perceptual and spatial skills being relatively unimpaired.
The Well Known Faces test, described in detail by Warrington and Sanders (1971), was adapted for testing retention by cued recall. The recall scores of the amnesic group are as impaired as on previous testing for all time periods sampled; again the severity of the retrograde deficit is clear cut. Their performance is strikingly improved with cued recall and the decay function obtained is remarkably similar to that of normal subjects tested by recall. Using the normal subjects recall scores as a reference point it is clear that there is no relative vulnerability of either recent events or for that matter of remote events. The decay over time indicates that the cue in itself is insufficient to generate the correct name.
Topographical disorientation can be dissociated in two levels, agnosic and amnesic. A case of topographical disorientation due to a glioma of the splenium of corpus callosum illustrates the dissociation between the topographical memory impairment and the normal performances on the perceptual topographic tests.
The recall of spatial location in patients with left or right temporal-lobe lesions was studied in two experiments, in which recall was tested either immediately after presentation of an array of objects, or after an intervening verbal task, a spatial task or an unfilled interval. Deficits were found only in patients with right temporal-lobe lesions that included extensive removal of the hippocampal region, and only when recall was tested after a delay. The presence of an intervening task in the delay interval did not accentuate the deficit. The results show that, despite a normal ability to encode location, patients with large right hippocampal lesions demonstrate an abnormally rapid forgetting of such information.
Four patients showing the syndrome of "topographical disorientation" are reported. Patients became unable to find their way, especially in unfamiliar surroundings, following a single lesion in the territory of the right posterior cerebral artery, as evidenced on CT-scan. Associated disturbances included: left hemianopia, mild face recognition problems, and various degree of impairment in face-learning and visual maze-learning tasks. Language, visuo-perceptive and constructional abilities, object and picture recognition were intact. Memory tests only showed a mild, generally non-significant, impairment of visual memory. As inferred from the lesion located in the 4 patients, this syndrome seems to be strongly related to damage to the right parahippocampal gyrus, a structure that thus appears crucial for specifically storing and/or retrieving visual information necessary to achieve orientation in the locomotor environment.
A SPECIFIC isolated and severe defect of memory, with preservation of other intellectual functions, including span of attention, may occur as the result of localized brain pathology. In amnesic patients the memory defect is so marked that performance on tests of recent memory declines sharply within a matter of minutes1.
Abnormal T2-weighted signal intensity in the hippocampus may be difficult to detect visually, and T2 mapping provides an objective means of assessing signal abnormality. We investigated 50 adult outpatients suffering from intractable partial epilepsy with MRI optimized to detect hippocampal and cortical gray matter abnormalities, and with MR T2 relaxation mapping. The range of normal hippocampal T2 relaxation times is small (99 to 106 msec), and the measurements are reproducible between observers. There were abnormal hippocampal T2 relaxation times in the hippocampus ipsilateral to the site of seizure origin in 70% of patients studied, with the more severe abnormality in the ipsilateral hippocampus in all cases. All hippocampal T2 measurements greater than 116 msec were associated with temporal lobe epilepsy and pathologic or MRI evidence of hippocampal sclerosis, or both. Bilateral abnormalities were present in 29% of cases with hippocampal sclerosis.
Proton magnetic resonance spectra include signals from N-acetylaspartate, creatine + phosphocreatine, and choline-containing compounds. Abnormalities in these signals can be used in the assessment of patients with intractable epilepsy. In particular, they provide a means of identifying metabolic abnormalities within the temporal lobes, detecting bilateral and diffuse pathology, and aiding lateralization of the seizure focus. The pathology demonstrated on MRS can also be related to cognitive dysfunction.
Studies of the non-human temporal lobe, particularly the hippocampus, confirm its significant role in learning and memory, particularly allocentric spatial mapping of the environment. The role of the human temporal lobes in topographical orientation was investigated by examining the formation of representations of a large-scale real-world environment after unilateral left and right temporal lobe surgery. Patients and normal control subjects viewed videotape presentations of overlapping routes through a novel urban area. Topographical orientation was then assessed across a range of parameters. Right temporal lobe lesions alone gave rise to deficits in making proximity judgements. However, on all other topographical orientation tasks both right and left temporal lobe lesion groups were impaired relative to the normal control group, but the two patient groups did not differ significantly from each other. These findings suggest that such is the nature of remembering and way-finding in the environment that the integrity of both human temporal lobes is required.
Studied the role of the hippocampal formation (HCF) in human spatial memory (SM). In Exp 1, 20 left and 20 right unilateral temporal lobe resection (TLR) patients together with age- and IQ-matched controls were tested in the Executive-Golf task. Significant impairment was seen on the right TLR group only. In Exp 2, the same Ss in Exp 1 were tested on the Rotating SM Task. Only the right TLR group had a significantly increased number of between search errors. In Exp 3, a further group of patients with unilateral lesions specific to the HCF were tested on the SM test. This group was compared with normal controls and further groups of left and right TLR patients. Only the right HCF and TLR group were impaired, the deficit being the same magnitude in both groups and found on both the context dependent and learning components of the task. A comment on these experiments and a corresponding reply are appended. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Patients with unilateral temporal lobe damage resulting from intractable temporal lobe epilepsy (TLE, n = 30) or from temporal lobe resection (temporal lobectomy, TLR, n = 47) were investigated on the Nine-box Maze. The task, analogous to the radial arm maze, was designed to compare spatial mapping and working memory theories of the functions of the hippocampus. The task provides measures of spatial, object, working and reference memory, incorporated into a within subjects design. The spatial component was designed to encourage the formation of allocentric rather than egocentric spatial representations. Spatial memory deficits were found (across working and reference memory components) in both TLE and TLR patients with right temporal lobe damage, with intact spatial memory in patients with corresponding left temporal lobe damage. Performance on the matched non-spatial (object) working memory component was equal to healthy controls for all groups. However all patient groups showed a deficit on object reference memory. These findings are discussed in relation to the underlying temporal lobe pathology and particularly atrophy of the hippocampal formation. Overall, the results support the cognitive mapping theory of hippocampal function, with the demonstration of a selective (and probably allocentric) spatial memory deficit in patients with right hippocampal damage.
One hundred patients with intractable temporal lobe epilepsy and 22 control subjects were scanned on a 1.5-T Siemens SP63 Magnetom scanner. A combination of hippocampal T2 mapping, hippocampal volume measurement corrected for intracranial volume, and inspection of hippocampal morphology on a hippocampal volume distribution graph compared with a control graph revealed previously undetected forms of bilateral hippocampal sclerosis and four false-positive diagnoses of hippocampal sclerosis made on visual inspection of the scans. A physiological asymmetry in the position of the hippocampi in 41% of control subjects and focal hippocampal atrophies in patients made measurement of the whole length of the hippocampus mandatory. The extent of hippocampal damage in patients with hippocampal sclerosis correlated with the number of secondary generalized seizures during a patient's lifetime. In contrast to patients with unilateral hippocampal sclerosis, patients with severe bilateral hippocampal sclerosis had no history of febrile convulsions. Twenty-six patients with intractable temporal lobe epilepsy had normal hippocampal magnetic resonance imaging measures and as a group were significantly older at the onset of habitual epilepsy than were patients with hippocampal sclerosis. In conclusion, a combination of quantitative magnetic resonance imaging techniques revealed a spectrum of hippocampal sclerosis and optimally defined boundaries of hippocampal normality. The spectrum of hippocampal sclerosis is related to the etiology, the number of secondary generalized seizures, and the age at onset of habitual epilepsy.
Damage to the human parietal cortex leads to disturbances of spatial perception and of motor behaviour. Within the parietal lobe, lesions of the superior and of the inferior lobule induce quite different, characteristic deficits. Patients with inferior (predominantly right) parietal lobe lesions fail to explore the contralesional part of space by eye or limb movements (spatial neglect). In contrast, superior parietal lobe lesions lead to specific impairments of goal-directed movements (optic ataxia). The observations reported in this paper support the view of dissociated functions represented in the inferior and the superior lobule of the human parietal cortex. They suggest that a spatial reference frame for exploratory behaviour is disturbed in patients with neglect. Data from these patients' visual search argue that their failure to explore the contralesional side is due to a disturbed input transformation leading to a deviation of egocentric space representation to the ipsilesional side. Data further show that this deviation follows a rotation around the earth-vertical body axis to the ipsilesional side rather than a translation towards that side. The results are in clear contrast to explanations that assume a lateral gradient ranging from a minimum of exploration in the extreme contralesional to a maximum in the extreme ipsilesional hemispace. Moreover, the failure to orient towards and to explore the contralesional part of space appears to be distinct from those deficits observed once an object of interest has been located and releases reaching. Although patients with neglect exhibit a severe bias of exploratory movements, their hand trajectories to targets in peripersonal space may follow a straight path. This result suggests that (i) exploratory and (ii) goal-directed behaviour in space do not share the same neural control mechanisms. Neural representation of space in the inferior parietal lobule seems to serve as a matrix for spatial exploration and for orienting in space but not for visuomotor processes involved in reaching for objects. Disturbances of such processes rather appear to be prominent in patients with more superior parietal lobe lesions and optic ataxia.
Medial temporal brain regions such as the hippocampal formation and parahippocampal cortex have been generally implicated in navigation and visual memory. However, the specific function of each of these regions is not yet clear. Here we present evidence that a particular area within human parahippocampal cortex is involved in a critical component of navigation: perceiving the local visual environment. This region, which we name the 'parahippocampal place area' (PPA), responds selectively and automatically in functional magnetic resonance imaging (fMRI) to passively viewed scenes, but only weakly to single objects and not at all to faces. The critical factor for this activation appears to be the presence in the stimulus of information about the layout of local space. The response in the PPA to scenes with spatial layout but no discrete objects (empty rooms) is as strong as the response to complex meaningful scenes containing multiple objects (the same rooms furnished) and over twice as strong as the response to arrays of multiple objects without three-dimensional spatial context (the furniture from these rooms on a blank background). This response is reduced if the surfaces in the scene are rearranged so that they no longer define a coherent space. We propose that the PPA represents places by encoding the geometry of the local environment.
Deficits in performance of both spatial and visual tasks are common following tissue loss in the right temporal lobe. Since spatial and visual attributes are frequently confounded in experimental tasks, we have studied patients following unilateral temporal lobectomy, in an attempt to determine which aspect mediates the observed deficits. Spatial and visual memory performance was compared in normal controls (n = 16), left temporal (LTL; n = 19) and right temporal (RTL; n = 19) lobectomy patients, by presentation of eight abstract designs in a spatial array for subsequent recall and recognition of the designs (visual memory) and recall of their spatial position (spatial memory). By varying the retention intervals for each group, all three groups were matched on both recall and recognition of the designs at sub-ceiling levels. In contrast, recall of the position of the designs (spatial memory), tested at equivalent delays to those of the visual memory tests, revealed a deficit in the RTL patients compared to both controls and LTL patients (p < 0.05). Magnetic resonance imaging (MRI) was used to quantify the extent of resection of the hippocampus and parahippocampal regions in the two patient groups and showed a significant correlation between hippocampal and parahippocampal removal and spatial memory in the RTL group only. These data support the notion of a disproportionately large involvement of the right hippocampus and adjacent regions in spatial memory.
A 70-year-old woman presented with pure topographical disorientation following haemorrhage in the right medial parietal lobe. She could not navigate in the real world despite good ability to draw maps, describe routes, and identify objects and buildings. Her performance on mental rotation, visual memory, and spatial learning tests also was normal. In contrast, she failed totally in a locomotor map test and in a task in which she was requested to judge viewpoints of buildings. Her highly selective topographical disorientation was probably caused by the inability to identify a viewpoint of a particular building. The lesion may have disconnected the association between the spatial information processed in the lateral parietal lobe and the visual memory mediated by the limbic system, which seems to be important for viewpoint dependent analysis.
Spatial memory tasks, performance of which is known to be sensitive to hippocampal lesions in the rat, or to medial temporal lesions in the human, were administered in order to investigate the effects of selective damage to medial temporal lobe structures of the human brain. The patients had undergone thermo-coagulation with a single electrode along the amygdalo-hippocampal axis in an attempt to alleviate their epilepsy. With this surgical technique, lesions to single medial temporal lobe structures can be carried out. The locations of the lesions were assessed by means of digital high-resolution magnetic resonance imaging and software allowing a 3-D reconstruction of the brain. A break in the collateral sulcus, dividing it into the anterior collateral sulcus and the posterior collateral sulcus is reported. This division may correspond to the end of the entorhinal/perirhinal cortex and the start of the parahippocampal cortex. The results confirmed the role of the right hippocampus in visuo-spatial memory tasks (object location, Rey-Osterrieth Figure with and without delay) and the left for verbal memory tasks (Rey Auditory Verbal Learning Task with delay). However, patients with lesions either to the right or to the left hippocampus were unimpaired on several memory tasks, including a spatial one, with a 30 min delay, designed to be analogous to the Morris water maze. Patients with lesions to the right parahippocampal cortex were impaired on this task with a 30 min delay, suggesting that the parahippocampal cortex itself may play an important role in spatial memory.
We report an 82-year-old woman who developed pure topographical disorientation after a cerebral infarction involving the isthmus of the right posterior cingulate gyrus. She lost her way in new environments such as the hospital, but not in old ones such as her own house. She correctly identified familiar or unfamiliar landscapes and buildings by photographs. Her failure to memorize a new route likely resulted from a loss of directional memory over a wide area. We suggest that the right posterior cingulate gyrus contributes to memorizing a new route.
The hippocampus is part of a system of structures in the medial temporal lobe that are essential for memory. One influential view of hippocampal function emphasizes its role in the acquisition and retrieval of spatial knowledge. By this view, the hippocampus constructs and stores spatial maps and is therefore essential for learning and remembering places, including those learned about long ago. We tested a profoundly amnesic patient (E.P.), who has virtually complete bilateral damage to the hippocampus and extensive damage to adjacent structures in the medial temporal lobe. We asked him to recall the spatial layout of the region where he grew up, from which he moved away more than 50 years ago. E.P. performed as well as or better than age-matched control subjects who grew up in the same region and also moved away. In contrast, E.P. has no knowledge of his current neighbourhood, to which he moved after he became amnesic. Our results show that the medial temporal lobe is not the permanent repository of spatial maps, and support the view that the hippocampus and other structures in the medial temporal lobe are essential for the formation of long-term declarative memories, both spatial and non-spatial, but not for the retrieval of very remote memories, either spatial or non-spatial.