Coordination of multiple memory systems

On the basis of lesions of different brain areas, several neural systems appear to be important for processing information regarding different types of learning and memory. This paper examines the development of pharmacological and neurochemical approaches to multiple memory systems from past studies of modulation of memory formation. The findings suggest that peripheral neuroendocrine mechanisms that regulate memory processing may target their actions toward those neural systems most engaged in the processing of learning and memory. In addition, measurements of acetylcholine release in different memory systems reveals extensive interactions between memory systems, some cooperative and some competitive. These results imply that many neural systems, often characterized as relatively independent, may in fact interact extensively, blurring the dependencies of different memory tasks on specific neural systems.     

Acetylcholine modulation of neural systems involved in learning and memory

Extensive evidence supports the view that cholinergic mechanisms modulate learning and memory formation. This paper reviews evidence for cholinergic regulation of multiple memory systems, noting that manipulations of cholinergic functions in many neural systems can enhance or impair memory for tasks generally associated with those neural systems. While parallel memory systems can be identified by combining lesions with carefully crafted tasks, most—if not all—tasks require the combinatorial participation of multiple neural systems. This paper offers the hypothesis that the magnitude of acetylcholine (ACh) release in different neural systems may regulate the relative contributions of these systems to learning. Recent studies of ACh release, obtained with in vivo microdialysis samples during training, together with direct injections of cholinergic drugs into different neural systems, provide evidence that release of ACh is important in engaging these systems during learning, and that the extent to which the systems are engaged is associated with individual differences in learning and memory.     

Parallel processing across neural systems: implications for a multiple memory system hypothesis

A common conceptualization of the organization of memory systems in brain is that different types of memory are mediated by distinct neural systems. Strong support for this view comes from studies that show double (or triple) dissociations between spatial, response, and emotional memories following selective lesions of hippocampus, striatum, and the amygdala. Here, we examine the extent to which hippocampal and striatal neural activity patterns support the multiple memory systems view. A comparison is made between hippocampal and striatal neural correlates with behavior during asymptotic performance of spatial and response maze tasks. Location- (or place), movement, and reward-specific firing patterns were found in both structures regardless of the task demands. Many, but not all, place fields of hippocampal and striatal neurons were similarly affected by changes in the visual and reward context regardless of the cognitive demands. Also, many, but not all, hippocampal and striatal movement-sensitive neurons showed significant changes in their behavioral correlates after a change in visual context, irrespective of cognitive strategy. Similar partial reorganization was observed following manipulations of the reward condition for cells recorded from both structures, again regardless of task. Assuming that representations that persist across context changes reflect learned information, we make the following conclusions. First, the consistent pattern of partial reorganization supports a view that the analysis of spatial, response, and reinforcement information is accomplished via an error-driven, or match-mismatch, algorithm across neural systems. Second, task-relevant processing occurs continuously within hippocampus and striatum regardless of the cognitive demands of the task. Third, given the high degree of parallel processing across allegedly different memory systems, we propose that different neural systems may effectively compete for control of a behavioral expression system. The strength of the influence of any one neural system on behavioral output is likely modulated by factors such as motivation, experience, or hormone status.     

An analysis of independence and interactions of brain substrates that subserve multiple attributes, memory systems, and underlying processes

It is proposed that memory is organized into event-based, knowledge-based, and rule-based memory systems. Furthermore, each system is composed of the same set of multiple attributes and characterized by a set of process oriented operating characteristics that are mapped onto multiple neural regions and interconnected neural circuits. Based on this theoretical model of memory, it is possible to investigate the independence and interaction among brain regions between any two systems for any of the proposed attributes or processes. This applies also to the investigation of independence and interactions between any two attributes within a system and between processes associated with a system for any of the proposed attributes. In this article, research evidence is presented to suggest that there are both dissociations and interactions between the hippocampus and caudate nucleus in mediating spatial and response attributes within the event-based memory system, between the hippocampus and the parietal cortex in subserving the spatial attribute within the event-based and knowledge-based memory systems, and between the hippocampus and the prefrontal cortex in subserving the spatial attribute within the event-based and rule-based memory systems.     

The role of stimulus ambiguity and movement in spatial navigation: a multiple memory systems analysis of location discrimination

This paper reviews recent findings about how rats navigate by learning to discriminate among locations. The assumption underlying the experiments and their interpretation is that the information required to do this is learned by three independent, parallel memory systems. One system processes cognitive information (or "knowledge"), a second system processes reinforced stimulus-response associations and a third processes Pavlovian conditioned responses in the form of stimulus-affect associations. The information stored in each system produces behavior that, in some cases, results in a location discrimination. The present experiments focus on three factors that influence what each system learns and whether the resulting memory produces behavior that results in a location discrimination. One factor is whether the locations to be discriminated can be identified by unique, unambiguous stimuli or whether they are ambiguously associated with the same stimuli. The second factor is whether the stimuli are observed passively or whether the rats move among them, voluntarily or involuntarily. The third factor is whether or not the rats perform specific reinforced responses in the presence of the stimuli. Instances of co-operative behavioral outputs from memory systems that facilitate location discriminations and of competitive outputs that impede discriminations are described.     

Extinction in multiple contexts does not necessarily make extinction less vulnerable to relapse

Three fear-conditioning experiments with rat subjects examined the effects of extinction in multiple contexts on a final relapse (renewal) effect that occurred when the extinguished fear cue was tested in a new context (Experiments 1 and 3) or in the context in which fear conditioning had first occurred (Experiment 2). Rats that received extinction in three contexts demonstrated more fear during extinction than rats that received the same number and temporal distribution of extinction trials in one context; extinction was partially lost with each context switch. Although extinction in multiple contexts thus had an impact on extinction behavior, it did not reduce the size of the final renewal effect. Fear during extinction was occasionally positively correlated with fear during final testing, but the two were never negatively correlated. The results suggest that extinction in multiple contexts does not necessarily weaken fear renewal, and that extinction procedures that generate high levels of responding in extinction do not necessarily make extinction learning less context-specific.     

No sex differences in spatial location memory for abstract designs

Previous research has demonstrated a female advantage, albeit imperfectly, on tests of object location memory where object identity information is readily available. However, spatial and visual elements are often confounded in the experimental tasks used. Here spatial and visual memory performance was compared in 30 men and 30 women by presenting 12 abstract designs in a spatial array for recall and recognition (visual memory) and spatial location ("object" location memory). Object location memory was measured via a sensitive absolute displacement score defined as the distance in mms between the position assigned to the object during recall and the actual position it originally occupied. There were no sex differences in either the visual or spatial location tests. Controlling for age and estimated IQ scores made no impact on the results. These data suggest an absence of a sex difference in purely visual and spatial aspects of object location memory.     

Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system

The aim of the present study was to test if the nigrostriatal pathway is an essential component for a water maze cued task learning and if it works independently of the hippocampal memory system. This hypothesis was tested using an animal model of Parkinson's disease in which male Wistar rats were lesioned in the substantia nigra pars compacta (SNc) by the intranigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), thus causing a partial depletion of striatal dopamine. SNc-lesioned and sham-operated animals were implanted bilaterally with guide cannulae above the dorsal hippocampus in order to be tested after the administration of 0.4 microl 2% lidocaine or saline into this structure. The animals were tested in a spatial or in a cued version of the water maze, memory tasks previously reported to model hippocampal-dependent spatial/relational and striatal-dependent S-R learning, respectively. Hippocampal inactivation, but not SNc lesion, impaired learning and memory in the spatial version of the water maze. An opposite situation was observed with the cued version. No significant interaction was observed between the SNc lesion and hippocampal inactivation conditions affecting scores in the spatial or in the cued version of the water maze. These results suggest that the nigrostriatal pathway is an essential part of the memory system that processes S-R learning and that it works independently of the hippocampal memory system that processes spatial/relational memories.     

Response production during extinction training is not sufficient for extinction of evaluative conditioning

Two high-powered experiments examined the role of evaluative response production in the extinction of evaluative conditioning (EC) by positioning EC in the procedural and conceptual framework of classical conditioning (CC). According to Rescorla's response inhibition hypothesis, more frequent responding during extinction training results in larger extinction during testing. Experiment 1 used three extinction conditions following response acquisition in an EC procedure: evaluative responses were measured only after extinction; after acquisition and after extinction; or were continuously measured after acquisition, during extinction and after extinction. Based on Rescorla's response inhibition hypothesis, we predicted that extinction of EC would be the highest in the third condition. Experiment 2 was aimed at further facilitating extinction of EC by encouraging participants to experience that their evaluation may change over the course of the experiment. To this end, half of the participants completed pre- and post-acquisition ratings prior to practicing continuous response expression in the extinction phase. Contrary to our predictions, no extinction of EC was observed in either of these experiments. We conclude that Rescorla's inhibition response hypothesis may not apply to EC and discuss the theoretical implications of this finding.     

Experiencing nearby locations together in time: the role of spatiotemporal contiguity in children's memory for location

Three studies investigated how experiencing nearby locations together in time influences memory for location. Seven-, 9-, and 11-year-old children and adults learned 20 object locations in a small-scale space. The space was divided into regions by lines or walls. In Study 1, participants learned the locations either region by region or in a random order. Following learning, participants replaced the objects without the aid of the dots marking the locations and the boundaries subdividing the space. They replaced the objects in any order they chose. After experiencing the locations in random orders during learning, only adults underestimated distances between locations belonging to the same group (i.e., region). Conversely, 9- and 11-year-old children and adults who had experienced the locations region by region during learning underestimated these distances. These findings suggest that experiencing nearby locations together in time increases the weight children assign to categorical information in their estimates of location. Results from Studies 2 and 3 in which participants learned the locations region by region and then replaced the objects region by region (Study 2) or in a random order (Study 3) were similar, highlighting the importance of spatiotemporal cues in memory for location. (c) 2002 Elsevier Science (USA).     

A putative role for neurogenesis in neurocomputational terms: Inferences from a hippocampal model

New neurons are generated daily in the hippocampus during adult life. They are integrated into the existing neuronal circuits according to several factors such as age, physical exercise and hormonal status. At present, the role of these new neurons is debated. Computational simulations of hippocampal function allow the effects of neurogenesis to be explored, at least from a computational perspective. The present work implements a model of neurogenesis in the hippocampus with artificial neural networks, based on a standard theoretical model of biologically plausible hippocampal circuits. The performance of the model in retrieval of a variable number of patterns or memories was evaluated (episodic memory evaluation). The model increased, in a phase subsequent to initial learning, the number of granular cells by 30% relative to their initial number. In contrast to a model without neurogenesis, the retrieval of recent memories was very significantly improved, although remotes memories were only slightly affected by neurogenesis. This increase in the quality of retrieval of new memories represents a clear advantage that we attribute to the neurogenesis process. This advantage becomes more significant for higher storage loads. The model presented here suggests an important functional role of neurogenesis on learning and memory.     

Sexual differences in memory in shiny cowbirds

Avian brood parasites depend on other species, the hosts, to raise their offspring. During the breeding season, parasitic cowbirds (Molothrus sp.) search for potential host nests to which they return for laying a few days after first locating them. Parasitic cowbirds have a larger hippocampus/telencephalon volume than non-parasitic species; this volume is larger in the sex involved in nest searching (females) and it is also larger in the breeding than in the non-breeding season. In nature, female shiny cowbirds Molothrus bonariensis search for nests without the male’s assistance. Here we test whether, in association with these neuroanatomical and behavioural differences, shiny cowbirds display sexual differences in a memory task in the laboratory. We used a task consisting of finding food whose location was indicated either by the appearance or the location of a covering disk. Females learnt to retrieve food faster than males when food was associated with appearance cues, but we found no sexual differences when food was associated with a specific location. Our results are consistent with the view that parasitism and its neuroanatomical correlates affect performance in memory tasks, but the effects we found were not in the expected direction, emphasising that the nature of avian hippocampal function and its sexual differences are not yet understood. Received: 30 April 1998 / Accepted after revision: 5 September 1998     

The role of the episodic buffer in working memory for language processing

A body of work has accumulated to show that the cognitive process of binding information from different mnemonic and sensory sources as well as in different linguistic modalities can be fractionated from general executive functions in working memory both functionally and neurally. This process has been defined in terms of the episodic buffer (Baddeley in Trends Cogn Sci 4(11):417–423, 2000). This paper considers behavioural, neuropsychological and neuroimaging data that elucidate the role of the episodic buffer in language processing. We argue that the episodic buffer seems to be truly multimodal in function and that while formation of unitary multidimensional representations in the episodic buffer seems to engage posterior neural networks, maintenance of such representations is supported by frontal networks. Although, the episodic buffer is not necessarily supported by executive processes and seems to be supported by different neural networks, it may operate in tandem with the central executive during effortful language processing. There is also evidence to suggest engagement of the phonological loop during buffer processing. The hippocampus seems to play a role in formation but not maintenance of representations in the episodic buffer of working memory.     

Role of estrogen in balancing contributions from multiple memory systems

In addition to modulating memory per se, estrogen alters the learning strategy used to solve a task, thereby regulating the quality of information processed by the brain. This review discusses estrogen's actions on cognition within a memory systems framework, highlighting our work with a variety of paradigms showing that learning strategy is sensitive to estrogen even when learning rate is not. Specifically, high levels of gonadal steroids, in particular, elevations in estrogen, bias female rats toward using hippocampal-sensitive approaches while low levels of gonadal steroids promote the use of non-hippocampal sensitive strategies. In light of findings from a variety of approaches involving the hippocampus in allocentric and the striatum in egocentric response patterns, it is likely that estrogen alters the relative participation of these, and most undoubtedly other, neural systems during cognition. Changes in neuromodulators such as acetylcholine that regulate other processes such as inhibitory tone and excitability reflect one mechanism by which estrogen may orchestrate learning and memory.     

Object-location memory: A lesion-behavior mapping study in stroke patients

Object-location memory is an important form of spatial memory, comprising different subcomponents that each process specific types of information within memory, i.e. remembering objects, remembering positions and binding these features in memory. In the current study we investigated the neural correlates of binding categorical (relative) or coordinate (exact) position information with objects in memory. Therefore, an object-location memory battery was used, including different task conditions assessing object-location memory, i.e. memory for position information per se, and binding object information with coordinate and categorical position information. Sixty-one stroke patients with focal brain lesions were examined and compared with 77 healthy matched controls. The lesion subtraction method was used to define the area of overlap. Results indicate an important role of the left posterior parietal cortex in the binding of both categorical and coordinate positions with object information. Additionally, the hippocampus seems important for categorical object-location memory. This suggests that categorical and coordinate object-location memory depend on similar cognitive and neural systems.     

Hippocampal region-specific contributions to memory performance in normal elderly

To investigate the relationship between regional hippocampal volume and memory in healthy elderly, 147 community-based volunteers, aged 55–83 years, were evaluated using magnetic resonance imaging, the Groton Maze Learning Test, Visual Reproduction and the Rey Auditory Verbal Learning Test. Hippocampal volumes were determined by interactive volumetry. We found greater age-related reduction in the volume of the hippocampal head relative to the tail. Right hippocampal tail volume correlated with spatial memory on the Groton Maze Learning Test while left hippocampal body volume was associated with delayed verbal memory. These associations were independent of age, sex, education and speed of processing and support the notion of functional differentiation along the long axis of the hippocampus.     

Cross-sensory transfer of reference frames in spatial memory

Two experiments investigated whether visual cues influence spatial reference frame selection for locations learned through touch. Participants experienced visual cues emphasizing specific environmental axes and later learned objects through touch. Visual cues were manipulated and haptic learning conditions were held constant. Imagined perspective taking when recalling touched objects was best from perspectives aligned with visually-defined axes, providing evidence for cross-sensory reference frame transfer. These findings advance spatial memory theory by demonstrating that multimodal spatial information can be integrated within a common spatial representation.     

Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction

There is much interest to understand the mechanisms leading to the establishment, maintenance, and extinction of fear memories. The amygdala has been critically involved in the processing of fear memories and a number of molecular changes have been implicated in this brain region in relation to fear learning. Although neural cell adhesion molecules (NCAMs) have been hypothesized to play a role, information available about their contribution to fear memories is scarce. We investigate here whether polysialylated NCAM (PSA-NCAM) contributes to auditory fear conditioning in the amygdala. First, PSA-NCAM expression was evaluated in different amygdala nuclei after auditory fear conditioning at two different shock intensities. Results showed that PSA-NCAM expression was increased 24 h post-training only in animals subjected to the highest shock intensity (1mA). Second, PSA-NCAM was cleaved in the basolateral amygdaloid complex through micro-infusions of the enzyme endoneuraminidase N, and the consequences of such treatment were investigated on the acquisition, consolidation, remote memory expression, and extinction of conditioned fear memories. Intra-amygdaloid cleavage of PSA-NCAM did not affect acquisition, consolidation or expression of remote fear memories. However, intra-amygdaloid PSA-NCAM cleavage enhanced fear extinction processes. These results suggest that upregulation of PSA-NCAM is a correlate of fear conditioning that is not necessary for the establishment of fear memory in the amygdala, but participates in mechanisms precluding fear extinction. These findings point out PSA-NCAM as a potential target for the treatment of psychopathologies that involve impairment in fear extinction.     

Developmental changes in infants’ visual short-term memory for location

To examine the development of visual short-term memory (VSTM) for location, we presented 6- to 12-month-old infants (N = 199) with two side-by-side stimulus streams. In each stream, arrays of colored circles continually appeared, disappeared, and reappeared. In the changing stream, the location of one or more items changed in each cycle; in the non-changing streams the locations did not change. Eight- and 12.5-month-old infants showed evidence of memory for multiple locations, whereas 6.5-month-old infants showed evidence of memory only for a single location, and only when that location was easily identified by salient landmarks. In the absence of such landmarks, 6.5-month-old infants showed evidence of memory for the overall configuration or shape. This developmental trajectory for spatial VSTM is similar to that previously observed for color VSTM. These results additionally show that infants’ ability to detect changes in location is dependent on their developing sensitivity to spatial reference frames.     

The role of crawling and walking experience in infant spatial memory

This research explored infants' use of place learning and cue learning in a locomotor task across the transition from crawling to walking. Novice and expert crawling and walking infants were observed in a novel locomotor task-finding a hidden goal location in a large space. In Experiment 1, infants were tested with distal landmarks. Infants with fewer than 6 weeks of experience, either crawling or walking, could not find the goal location. All infants with more locomotor experience were more successful. Learning did not transfer across the transition to walking. In Experiment 2, novice and expert crawlers and walkers were tested with a direct landmark. Again, novice crawlers and walkers with fewer than 6 weeks of experience could not find the goal, whereas those with more experience could. Taken together, these findings suggest that infants' spatial learning is inextricably linked to mode of locomotion.