The effects of lesions to the anterior thalamic nuclei on object-place associations in rats

Rats with lesions of the anterior nuclei of the thalamus were trained postoperatively on two spatial conditional associative learning tasks. In the first task, the rats were required to choose one or the other of two objects depending on the location in which they were found. In the second task, the animals learned to turn left or right depending on which one of two visual cues was presented. A third experiment examined the effects of damage to the anterior thalamic nuclei on the eight-arm radial maze, a spatial working memory task. Damage of the anterior thalamic nuclei impaired performance on the radial maze task and the conditional task requiring associations between objects and their location. By contrast, rats with anterior thalamic lesions were able to acquire, at a rate comparable with that of operated control animals, the conditional task requiring associations between objects and body turns. These findings suggest that lesions to the anterior thalamic nuclei result in a general impairment in learning about allocentric spatial information without disrupting the learning of egocentric spatial information.     

Perirhinal cortex involvement in allocentric spatial learning in the rat: Evidence from doubly marked tasks

It has recently been suggested that the different cortices of the medial temporal lobe support a mixture of object and spatial processing functions, challenging the anterior model that emphasized a strict functional differentiation between regions. However, for some structures, the perirhinal cortex (Prh) for example, a number of studies using lesion methods have shown a profound deficit exclusively in tasks involving object learning but not allocentric spatial learning. It may be that the learning paradigms used in previous studies have not been sensitive enough to detect a possible allocentric deficit in Prh‐lesioned animals. To examine whether Prh lesions critically affect allocentric spatial learning, experimental and control rats were trained in two doubly marked navigation tasks. In experiment 1, the use of either one of two different memory systems, allocentric versus egocentric, made it possible to locate the goal arm in a four‐arm radial maze. In experiment 2, rats had to choose between an allocentric versus a S‐R/habit strategy, both of which predicted the location of the goal arm. Results showed that both experimental and control animals learned both navigation tasks well, reaching the same level of performance at the end of training. However, a probe test performed 1 day after the learning ended revealed that Prh‐damaged animals learned both tasks predominantly using a non‐allocentric strategy. Specifically, in lesioned subjects the percentage of egocentric correct responses (experiment 1) and the percentage of habit‐based correct responses (experiment 2) was significantly higher than in the control rats. On the other hand, in both experiments, control rats in the probe test presented a significantly higher number of allocentric correct responses than the lesioned subjects. These results clearly suggest that Prh is normally needed for using allocentric strategies in order to solve a navigation problem. © 2017 Wiley Periodicals, Inc.     

Posterior parahippocampal gyrus lesions in the human impair egocentric learning in a virtual environment

Functional imaging studies have shown that the posterior parahippocampal gyrus (PHG) is involved in allocentric (world-centered) object and scene recognition. However, the putative role of the posterior PHG in egocentric (body-centered) spatial memory has received only limited systematic investigation. Thirty-one subjects with pharmacoresistant medial temporal lobe epilepsy (TLE) and temporal lobe removal were compared with 19 matched healthy control subjects on a virtual reality task affording the navigation in a virtual maze (egocentric memory). Lesions of the hippocampus and PHG of TLE subjects were determined by three-dimensional magnetic resonance imaging volumetric assessment. The results indicate that TLE subjects with right-sided posterior PHG lesions were impaired on virtual maze acquisition when compared with controls and TLE subjects with anterior PHG lesions. Larger posterior PHG lesions were significantly related to stronger impairments in virtual maze performance. Our results point to a role of the right-sided posterior PHG for the representation and storage of egocentric information. Moreover, access to both allocentric and egocentric streams of spatial information may enable the posterior PHG to construct a global and comprehensive representation of spatial environments.     

Allocentric memory impaired and egocentric memory intact as assessed by virtual reality in recent-onset schizophrenia

Present evidence suggests that schizophrenia is associated with explicit memory deficits, whereas implicit memory seems to be largely preserved. Virtual reality studies on declarative allocentric memory in schizophrenia are rare, and studies on implicit egocentric memory in schizophrenia are lacking. However, virtual realities have a major advantage for the assessment of spatial navigation and memory formation, as computer-simulated first-person environments can simulate navigation in a large-scale space. Twenty-five subjects with recent-onset schizophrenia were compared with 25 healthy matched control subjects on two virtual reality tasks affording the navigation and learning of a virtual park (allocentric memory) and a virtual maze (egocentric memory). Compared with control subjects, schizophrenia subjects were significantly impaired in learning the virtual park. However, schizophrenia subjects were as able as control subjects to learn the virtual maze. Stronger disorganized symptoms of schizophrenia subjects were significantly related to more errors on the virtual maze. It is concluded that egocentric spatial learning adds to the many other implicit cognitive skills being largely preserved in schizophrenia. Possibly, the more global neural network supporting egocentric spatial learning is less affected than the declarative hippocampal memory system in early stages of schizophrenia and may offer opportunities for compensation in the presence of focal deficits.     

Different effects of unilateral and bilateral hippocampal lesions in rats on the performance of radial maze and odor-paired associate tasks

The hippocampus plays an important role in the declarative or explicit memory in humans and is necessary for allocentric spatial learning and olfactory memory in animals. In primates and rodents, the bilateral hemispheres of the brain (especially the forebrain) symmetrically and asymmetrically contribute to diverse cognitive manipulations. In this study, we investigated the role of the hippocampus in spatial memory and in odor-paired associate memory by unilaterally or bilaterally lesioning this region in rats. The bilateral removal, but not the unilateral removal, of the hippocampus impaired both the acquisition of spatial working memory in the radial maze task and the retrieval of maze performance tested 1 month after the acquisition trials. In contrast, neither bilateral nor unilateral removal impaired the odor-paired associate learning. These findings suggest that the hippocampus is critical to the spatial memory, and that a unilateral hippocampus is sufficient for executing a spatial task. The present results also indicate that the hippocampus plays a minor role in odor-dominated associate learning and that some kinds of memories in rats may be processed independently by the left or right hippocampus.     

Effects of the monoamine oxidase A inhibitor moclobemide on hippocampal plasticity in GR-impaired transgenic mice

A reduction in glucocorticoid receptor (GR) function leads to hippocampus-dependent allocentric spatial learning deficits, altered novelty exploration and disrupted hippocampal long-term potentiation (LTP) in transgenic mice expressing a GR antisense construct. After continuous long-term treatment of these mice with moclobemide (a reversible inhibitor of monoamine oxidase A), spatial navigation performance but not accuracy improved during initial acquisition. These changes were associated with a shift of the threshold for the induction of hippocampal LTP at low stimulation frequencies. Moreover, novel object exploration increased in both control and transgenic animals following long-term treatment with moclobemide. These findings open the possibility that antidepressants might improve hippocampal function under conditions of impaired stress hormone regulation, and that these drugs might in part act through this mechanism to attenuate cognitive deficiency in disorders such as depression.     

Egocentric memory impaired and allocentric memory intact as assessed by virtual reality in subjects with unilateral parietal cortex lesions

Present evidence suggests that medial temporal cortices subserve allocentric representation and memory, whereas egocentric representation and memory mainly depends on inferior and superior parietal cortices. Virtual reality environments have a major advantage for the assessment of spatial navigation and memory formation, as computer-simulated first-person environments can simulate navigation in a large-scale space. However, virtual reality studies on allocentric memory in subjects with cortical lesions are rare, and studies on egocentric memory are lacking. Twenty-four subjects with unilateral parietal cortex lesions due to infarction or intracerebral haemorrhage (14 left-sided, 10 right-sided) were compared with 36 healthy matched control subjects on two virtual reality tasks affording to learn a virtual park (allocentric memory) and a virtual maze (egocentric memory). Subjects further received a comprehensive clinical and neuropsychological investigation, and MRI lesion assessment using T₁, T₂ and FLAIR sequences as well as 3D MRI volumetry at the time of the assessment. Results indicate that left- and right-sided lesioned subjects did not differ on task performance. Compared with control subjects, subjects with parietal cortex lesions were strongly impaired learning the virtual maze. On the other hand, performance of subjects with parietal cortex lesions on the virtual park was entirely normal. Volumes of the right-sided precuneus of lesioned subjects were significantly related to performance on the virtual maze, indicating better performance of subjects with larger volumes. It is concluded that parietal cortices support egocentric navigation and imagination during spatial learning in large-scale environments.     

Trends in comorbid sickle cell disease among stroke patients

BackgroundVisuospatial skills including spatial navigation are known to be impaired in Huntington's disease. Spatial navigation comprises two navigational frameworks, allocentric and egocentric. Several studies have associated the allocentric navigation with the hippocampus and the egocentric navigation with the striatum. The striatum is predominantly impaired from the early stages of Huntington's disease.ObjectiveTo find whether spatial navigation impairment is present in the early stages of Huntington's disease and to test the hypothesis that the egocentric navigation is predominantly affected compared to the allocentric navigation.MethodsIn nineteen patients with Huntington's disease the egocentric and the allocentric navigation skills were tested using the Blue Velvet Arena, a human analog of Morris Water Maze, and compared to nineteen age and gender-matched healthy controls. Cognitive functions, with emphasis on the executive functions, were also assessed.ResultsThe spatial navigation skills deteriorated with the increasing motor impairment in Huntington's disease. These changes only became apparent in patients with moderate functional impairment. No difference between the egocentric and the allocentric skills was seen.DiscussionSpatial navigation deficit is not an early marker of the cognitive dysfunction in Huntington's disease. We speculate that the striatal circuitry that is known to degenerate early in the course of Huntington's disease is not directly associated with the spatial navigation.     

Egocentric and allocentric memory as assessed by virtual reality in individuals with amnestic mild cognitive impairment

Present evidence suggests that medial temporal cortices subserve allocentric representation and memory, whereas egocentric representation and memory also depends on parietal association cortices and the striatum. Virtual reality environments have a major advantage for the assessment of spatial navigation and memory formation, as computer-simulated first-person environments can simulate navigation in a large-scale space. Twenty-nine patients with amnestic MCI (aMCI) were compared with 29 healthy matched controls on two virtual reality tasks affording to learn a virtual park (allocentric memory) and a virtual maze (egocentric memory). Participants further received a neuropsychological investigation and MRI volumetry at the time of the assessment. Results indicate that aMCI patients had significantly reduced size of the hippocampus bilaterally and the right-sided precuneus and inferior parietal cortex. aMCI patients were severely impaired learning the virtual park and the virtual maze. Smaller volumes of the right-sided precuneus were related to worse performance on the virtual maze. Participants with striatal lacunar lesions committed more errors than participants without such lesions on the virtual maze but not on the virtual park. aMCI patients later converting to dementia (n = 15) had significantly smaller hippocampal size when compared with non-converters (n = 14). However, both groups did not differ on virtual reality task performance. Our study clearly demonstrates the feasibility of virtual reality technology to study spatial memory deficits of persons with aMCI. Future studies should try to design spatial virtual reality tasks being specific enough to predict conversion from MCI to dementia and conversion from normal to MCI.     

Cholinergic receptor blockade in prefrontal cortex and lesions of the nucleus basalis: implications for allocentric and egocentric spatial memory in rats

In this study we have examined the involvement of the prefrontal cortex (PFC) along with the Nucleus basalis magnocellularis (NBM) in two types of spatial navigation tasks. We evaluated the effects of excitotoxic (ibotenate-induced) lesions of the NBM in an allocentric and an egocentric task in the Morris water maze, using sham operations for a comparison. In both cases we also assessed the effects of local cholinergic receptor blockade in the PFC by infusing the muscarinic receptor antagonist scopolamine (4 or 20 microg). Anatomically, the results obtained showed that this lesion produced a profound loss of acetylcholinesterase (AChE) positive cells in the NBM, and a loss of AChE positive fibres in most of the neocortex, but hardly in the medial PFC. Behaviourally, such lesions led to a severe impairment in the allocentric task. Intraprefrontal infusions of scopolamine led to a short-lasting impairment in task performance when the high dose was used. In the second experiment, using the same surgical manipulations, we examined the performance in the egocentric task. Like in the allocentric task animals with NBM lesions were also impaired, but with continued training they acquired a level of performance similar to the sham-operated ones. This time, infusions of scopolamine in the medial PFC led to a severe disruption of performance in both groups of animals. We conclude that acetylcholine in the medial PFC is important for egocentric but not allocentric spatial memory, whereas the NBM is involved in the learning of both tasks, be it to a different degree.     

Neural encoding of objects relevant for navigation and resting state correlations with navigational ability

Objects along a route can help us to successfully navigate through our surroundings. Previous neuroimaging research has shown that the parahippocampal gyrus (PHG) distinguishes between objects that were previously encountered at navigationally relevant locations (decision points) and irrelevant locations (nondecision points) during simple object recognition. This study aimed at unraveling how this neural marking of objects relevant for navigation is established during learning and postlearning rest. Twenty-four participants were scanned using fMRI while they were viewing a route through a virtual environment. Eye movements were measured, and brain responses were time-locked to viewing each object. The PHG showed increased responses to decision point objects compared with nondecision point objects during route learning. We compared functional connectivity between the PHG and the rest of the brain in a resting state scan postlearning with such a scan prelearning. Results show that functional connectivity between the PHG and the hippocampus is positively related to participants' self-reported navigational ability. On the other hand, connectivity with the caudate nucleus correlated negatively with navigational ability. These results are in line with a distinction between egocentric and allocentric spatial representations in the caudate nucleus and the hippocampus, respectively. Our results thus suggest a relation between navigational ability and a neural preference for a specific type of spatial representation. Together, these results show that the PHG is immediately involved in the encoding of navigationally relevant object information. Furthermore, they provide insight into the neural correlates of individual differences in spatial ability.     

A virtual reality-based FMRI study of reward-based spatial learning

Although temporo-parietal cortices mediate spatial navigation in animals and humans, the neural correlates of reward-based spatial learning are less well known. Twenty-five healthy adults performed a virtual reality fMRI task that required learning to use extra-maze cues to navigate an 8-arm radial maze and find hidden rewards. Searching the maze in the spatial learning condition compared to the control conditions was associated with activation of temporo-parietal regions, albeit not including the hippocampus. The receipt of rewards was associated with activation of the hippocampus in a control condition when using the extra-maze cues for navigation was rendered impossible by randomizing the spatial location of cues. Our novel experimental design allowed us to assess the differential contributions of the hippocampus and other temporo-parietal areas to searching and reward processing during reward-based spatial learning. This translational research will permit parallel studies in animals and humans to establish the functional similarity of learning systems across species; cellular and molecular studies in animals may then inform the effects of manipulations on these systems in humans, and fMRI studies in humans may inform the interpretation and relevance of findings in animals.     

Effects of hippocampal lesions on patterned motor learning in the rat

Motor skill learning in rats has been linked to cerebellar function as well as to cortical and striatal influences. The present study evaluated the contribution of the hippocampus to motor learning. Adult male rats received electrolytic lesions designed to selectively destroy the hippocampus; a sham-lesioned group of animals served as a control. The animals with hippocampal lesions acquired a patterned motor learning task as well as sham controls. In contrast, rats with hippocampal lesions were impaired in spatial, but not cued, learning in the Morris water maze. In addition, lesioned rats showed profound impairment in the novel object recognition memory task, when a 1-h delay was used between training and testing. Taken together, these results suggest that the hippocampus is not necessary during acquisition of the motor learning task.     

Ibotenate Lesions of Hippocampus and/or Subiculum: Dissociating Components of Allocentric Spatial Learning

This study examined the effects of ibotenic acid-induced lesions of the hippocampus, subiculum and hippocampus +/- subiculum upon the capacity of rats to learn and perform a series of allocentric spatial learning tasks in an open-field water maze. The lesions were made by infusing small volumes of the neurotoxin at a total of 26 (hippocampus) or 20 (subiculum) sites intended to achieve complete target cell loss but minimal extratarget damage. The regional extent and axon-sparing nature of these lesions was evaluated using both cresyl violet and Fink - Heimer stained sections. The behavioural findings indicated that both the hippocampus and subiculum lesions caused impairment to the initial postoperative acquisition of place navigation but did not prevent eventual learning to levels of performance almost as effective as those of controls. However, overtraining of the hippocampus + subiculum lesioned rats did not result in significant place learning. Qualitative observations of the paths taken to find a hidden escape platform indicated that different strategies were deployed by hippocampal and subiculum lesioned groups. Subsequent training on a delayed matching to place task revealed a deficit in all lesioned groups across a range of sample choice intervals, but the subiculum lesioned group was less impaired than the group with the hippocampal lesion. Finally, unoperated control rats given both the initial training and overtraining were later given either a hippocampal lesion or sham surgery. The hippocampal lesioned rats were impaired during a subsequent retention/relearning phase. Together, these findings suggest that total hippocampal cell loss may cause a dual deficit: a slower rate of place learning and a separate navigational impairment. The prospect of unravelling dissociable components of allocentric spatial learning is discussed.     

Both the dorsal hippocampus and the dorsolateral striatum are needed for rat navigation in the Morris water maze

The multiple memory systems theory proposes that the hippocampus and the dorsolateral striatum are the core structures of the spatial/relational and stimulus-response (S-R) memory systems, respectively. This theory is supported by double dissociation studies showing that the spatial and cue (S-R) versions of the Morris water maze are impaired by lesions in the dorsal hippocampus and dorsal striatum, respectively. In the present study we further investigated whether adult male Wistar rats bearing double and bilateral electrolytic lesions in the dorsal hippocampus and dorsolateral striatum were as impaired as rats bearing single lesions in just one of these structures in learning both versions of the water maze. Such a prediction, based on the multiple memory systems theory, was not confirmed. Compared to the controls, the animals with double lesions exhibited no improvement at all in the spatial version and learned the cued version very slowly. These results suggest that, instead of independent systems competing for holding control over navigational behaviour, the hippocampus and dorsal striatum both play critical roles in navigation based on spatial or cue-based strategies.     

6-Hydroxydopamine-Induced Dopamine Reductions in the Nucleus Accumbens,but not the Medial Prefrontal Cortex,Impair Cincinnati Water Maze Egocentric and Morris Water Maze Allocentric Navigation in Male Sprague–Dawley Rats

The nucleus accumbens (Nacc) and medial prefrontal cortex (mPFC) receive dopaminergic innervation from the ventral tegmental area and are involved in learning. Male rats with 6-hydroxydopamine (6-OHDA)-induced dopaminergic and noradrenergic reductions in the Nacc or mPFC were tested for allocentric and egocentric learning to determine their role in these forms of neuroplasticity. mPFC dopaminergic and noradrenergic reductions did not result in changes to either type of learning or memory. Nacc dopaminergic and noradrenergic reductions resulted in allocentric learning and memory deficits in the Morris water maze (MWM) on acquisition, reversal, and probe trials. MWM cued performance was also affected, but straight-channel swim times and swim speed during hidden platform trials in the MWM were not affected. Nacc dopaminergic and noradrenergic reductions also impaired egocentric learning in the Cincinnati water maze (CWM). Nacc-lesioned animals tested in the CWM in an alternate path through the maze were not significantly affected. 6-OHDA injections in the Nacc resulted in 63 % dopamine and 62 % norepinephrine reductions in the Nacc and 23 % reductions in adjacent dorsal striatum. 6-OHDA injections in the mPFC resulted in 88 % reductions in dopamine and 59 % reductions in norepinephrine. Hence, Nacc dopamine and/or norepinephrine play a role in egocentric and allocentric learning and memory, while mPFC dopamine and norepinephrine do not.     

The effects of overtraining in the Morris water maze on allocentric and egocentric learning strategies in rats

Animals can use both allocentric and egocentric strategies to learn a spatial task. Our results suggest that allocentric cues are more dominant than idiothetic cues in guiding navigation. Animals do not necessarily learn an egocentric strategy automatically, instead they probably hold just one solution to any particular task at a time until forced to learn an alternative strategy. Further, with overtraining animals do not always switch from allocentric to an egocentric learning strategy perhaps challenging suggestions of a stored hierarchy of strategies.     

Striatal lesions interfere with acquisition of a complex maze task in rats

The 14-unit T-maze has proven to be a valuable tool for investigating age-associated memory impairment (AAMI). While another task widely used to evaluate AAMI, the water maze, is primarily used to evaluate allocentric hippocampal-dependent spatial memory, the 14-unit T-maze can assess egocentric procedural memory. Although several brain structures, e.g. hippocampus, parietal cortex, have been implicated in acquisition and retention performance in the 14-unit T-maze, there has been no evaluation of the involvement of the striatum, a brain region implicated in procedural learning and memory. The current study revealed that excitotoxic lesions of the medial or lateral striatum significantly impaired acquisition, as measured by errors and latency, on this task without disruption of motor function. These results indicate that the 14-unit T-maze most likely is requires a large egocentric procedural learning component, and previously observed AAMI may involve age-related dysfunction of the striatum.     

The Effects of Lesions to the Mammillary Region and the Hippocampus on Conditional Associative Learning by Rats

Rats with extensive lesions to the mammillary body region, the hippocampus, or rats which had received a control operation were trained postoperatively on two visuo-spatial conditional associative learning tasks in which they had to learn to associate spatial cues with particular visual/auditory stimuli. The animals were subsequently trained on a spatial working memory task, the eight-arm radial maze. Rats with lesions to the mammillary body region were able to acquire the conditional associative learning tasks at a rate comparable to that of operated control animals, whereas those with hippocampal lesions were not. By contrast, rats with a lesion of the mammillary body region or the hippocampus were significantly impaired in comparison with the operated control animals in the radial maze. The findings suggest that lesions to the mammillary body region impair spatial working memory without affecting the capacity to associate particular exteroceptive cues with spatial locations.     

A comparison of egocentric and allocentric spatial memory in a patient with selective hippocampal damage

The spatial memory of a single patient (YR) was investigated. This patient, who had relatively selective bilateral hippocampal damage, showed the pattern of impaired recall but preserved item recognition on standardised memory tests that has been suggested by Aggleton and Shaw [Aggleton JP, Shaw C. Amnesia and recognition memory: a reanalysis of psychometric data. Neuropsychologia 1996;34:51-62] to be a consequence of Papez circuit lesions. YR was tested on three recall tests and one recognition test for visuospatial information. The initial recall test assessed visuospatial memory over very short unfilled delays and YR was not significantly impaired. This test was then modified to test recall of allocentric and egocentric spatial information separately after filled delays of between 5 and 60 s. YR was found to be more impaired at recalling allocentric than egocentric information after a 60 s interval with a tendency for the impairment to increase up to this delay. Recognition of allocentric spatial information was also assessed after delays of 5 and 60 s. YR was impaired after the 60 s delay. The results suggest that the human hippocampus has a greater involvement in allocentric than egocentric spatial memory, and that this most likely concerns the consolidation of allocentric information into long-term memory rather than the initial encoding of allocentric spatial information. The findings also suggest that YR's item recognition/free recall deficit pattern reflects a problem retrieving or storing certain kinds of associative information.