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.     

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.     

A model of episodic memory: Mental time travel along encoded trajectories using grid cells

The definition of episodic memory includes the concept of mental time travel: the ability to re-experience a previously experienced trajectory through continuous dimensions of space and time, and to recall specific events or stimuli along this trajectory. Lesions of the hippocampus and entorhinal cortex impair human episodic memory function and impair rat performance in tasks that could be solved by retrieval of trajectories. Recent physiological data suggests a novel model for encoding and retrieval of trajectories, and for associating specific stimuli with specific positions along the trajectory. During encoding in the model, external input drives the activity of head direction cells. Entorhinal grid cells integrate the head direction input to update an internal representation of location, and drive hippocampal place cells. Trajectories are encoded by Hebbian modification of excitatory synaptic connections between hippocampal place cells and head direction cells driven by external action. Associations are also formed between hippocampal cells and sensory stimuli. During retrieval, a sensory input cue activates hippocampal cells that drive head direction activity via previously modified synapses. Persistent spiking of head direction cells maintains the direction and speed of the action, updating the activity of entorhinal grid cells that thereby further update place cell activity. Additional cells, termed arc length cells, provide coding of trajectory segments based on the one-dimensional arc length from the context of prior actions or states, overcoming ambiguity where the overlap of trajectory segments causes multiple head directions to be associated with one place. These mechanisms allow retrieval of complex, self-crossing trajectories as continuous curves through space and time.     

Immediate early gene activation in hippocampus and dorsal striatum: effects of explicit place and response training

Evidence from lesion, electrophysiological, and neuroimaging studies support the hypothesis that the hippocampus and dorsal striatum process afferent inputs in such a way that each structure regulates expression of different behaviors in learning and memory. The present study sought to determine whether rats explicitly trained to perform one of two different learning strategies, spatial or response, would display disparate immediate early gene activation in hippocampus and striatum. c-Fos and Zif268 immunoreactivity (IR) was measured in both hippocampus and striatum 30 or 90 min following criterial performance on a standard plus-maze task (place learners) or a modified T-maze task (response learners). Place and response learning differentially affected c-Fos-IR in striatum but not hippocampus. Specifically, explicit response learning induced greater c-Fos-IR activation in two subregions of the dorsal striatum. This increased c-Fos-IR was dependent upon the number of trials performed prior to reaching behavioral criterion and accuracy of performance during post-testing probe trials. Quantification of Zif268-IR in both hippocampus and striatum failed to distinguish between place and response learners. The changes in c-Fos-IR occurred 30 min, but not 90 min, post-testing. The synthesis of c-Fos early in testing could reflect the recruitment of key structures in learning. Consequently, animals that were able to learn the response task efficiently displayed greater amounts of c-Fos-IR in dorsal striatum.     

Honeybees (Apis mellifera) holding on to memories: response competition causes retroactive interference effects

Five experiments on honeybees examined how the learning of a second task interferes with what was previously learned. Free flying bees were tested for landmark-based memory in variations on a paradigm of retroactive interference. Bees first learned Task 1, were tested on Task 1 (Test 1), then learned Task 2, and were tested again on Task 1 (Test 2). A 60-min delay (waiting in a box) before Test 2 caused no performance decrements. If the two tasks had conflicting response requirements, (e.g., target right of a green landmark in Task 1 and left of a blue landmark in Task 2), then a strong decrement on Test 2 was found (retroactive interference effect). When response competition was minimised during training or testing, however, the decrement on Test 2 was small or nonexistent. The results implicate response competition as a major contributor to the retroactive interference effect. The honeybee seems to hold on to memories; new memories do not wipe out old ones.     

Manipulations of start and food locations affect navigation on a foraging task

Rats were able to search multiple food cups in a foraging task and successfully return to a fixed, but not a variable, start location. Reducing the number of food cups to be searched resulted in an improvement in performance in the variable start condition. Performance was better when only one or two food cups had to be visited but was still impaired if the food was not found in the first cup searched. Variable start locations impaired performance when only one food cup had to be searched, if that cup was moved over the table. These findings suggest that there is an interaction between memory processes and the navigational processes that allows an animal to return to its start location after a foraging trip. It appears that a fixed location for the food or the start point of a foraging trip is a necessary precondition for accurate performance.     

Judgements of relative direction: The effect of task instructions on spatial recall

One of the most widely used tasks in the spatial memory literature is the judgement of relative direction (JRD) test. The present investigation examined the hypothesis that standard JRD task demands bias spatial recall. In two experiments, participants' recall of small-scale layouts as measured by standard JRD tests (in which the relationship between objects was employed to establish imagined orientations within the learned scene) was compared with recall as measured by novel JRD tasks. The novel tasks emphasized either the internal front/back and left/right axes of individual objects (Experiment 1) or extrinsic spatial cues (Experiment 2). Spatial recall was found to reflect the reference cues emphasized by the JRD task in Experiment 1 and by the novel task in Experiment 2. The finding that directional judgements tended to reflect a frame of reference aligned with the set of cues emphasized by task demands suggests that the nature of the task employed to test knowledge can have an effect on spatial recall.     

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.     

On the Nature of Nonverbal Working Memory Fractionation: A Case of Selective Spatial Short-Term Memory Deficit in a Child

Several lines of research on adult subjects demonstrate a visual/spatial fractionation of nonverbal working memory (WM), while behavioral studies on normal children support the idea of a static/dynamic distinction. In the present paper, we report a child (Z.M.) who failed on nonverbal WM tasks. To verify the nature of his defect, we carried out two experiments: in Experiment 1, Z.M. failed on spatial WM tasks but not on visual WM tasks and was not affected by the static/dynamic format of stimulus presentation; in Experiment 2, this visual/spatial dissociation was extended to the imagery domain. These results are best accounted for within the visual/spatial fractionation of WM and confirmed the role of WM in mental imagery. Clinical and rehabilitative implications of the present findings are also discussed.     

Effects of chronic cocaine administration on spatial learning and hippocampal spine density in two genetically different strains of rats

Lewis and Fischer-344 rats have been proposed as an addiction model because of their differences in addiction behaviour. It has been suggested that drug addiction is related to learning and memory processes and depends on individual genetic background. We have evaluated learning performance using the eight-arm radial maze (RAM) in Lewis and Fischer-344 adult rats undergoing a chronic treatment with cocaine. In order to study whether morphological alterations were involved in the possible changes in learning after chronic cocaine treatment, we counted the spine density in hippocampal CA1 neurons from animals after the RAM protocol. Our results showed that Fischer-344 rats significantly took more time to carry out test acquisition and made a greater number of errors than Lewis animals. Nevertheless, cocaine treatment did not induce changes in learning and memory processes in both strains of rats. These facts indicate that there are genetic differences in spatial learning and memory that are not modified by the chronic treatment with cocaine. Moreover, hippocampal spine density is cocaine-modulated in both strains of rats. In conclusion, cocaine induces similar changes in hippocampal neurons morphology that are not related to genetic differences in spatial learning in the RAM protocol used here.     

Theoretical accounts of spatial learning: A neurobiological view (commentary on Pearce, 2009)

Theories of learning have historically taken, as their starting point, the assumption that learning processes have universal applicability. This position has been argued on grounds of parsimony, but has received two significant challenges: first, from the observation that some kinds of learning, such as spatial learning, seem to obey different rules from others, and second, that some kinds of learning take place in processing modules that are separate from each other. These challenges arose in the behavioural literature but have since received considerable support from neurobiological studies, particularly single neuron studies of spatial learning, confirming that there are indeed separable (albeit highly intercommunicating) processing modules in the brain, which may not always interact (within or between themselves) according to classic associative principles. On the basis of these neurobiological data, reviewed here, it is argued that rather than assuming universality of associative rules, it is more parsimonious to assume sets of locally operating rules, each specialized for a particular domain. By this view, although almost all learning is associative in one way or another, the behavioural-level characterization of the rules governing learning may vary depending on which neural modules are involved in a given behaviour. Neurobiological studies, in tandem with behavioural studies, can help reveal the nature of these modules and the local rules by which they interact.     

Walking reduces the gap between encoding and sensorimotor alignment effects in spatial updating of described environments

Spatial updating allows people to keep track of the self-to-object relations during movement. Previous studies demonstrated that physical movement enhanced spatial updating in remote environments, but failed to find the same effect in described environments. However, these studies mainly considered rotation as a physical movement, without examining other types of movement, such as walking. We investigated how walking affects spatial updating within described environments. Using the judgement of relative directions task, we compared the effects of imagination of rotation, physical rotation, and walking on spatial updating. Spatial updating was evaluated in terms of accuracy and response times in different perspectives, and by calculating two indexes, namely the encoding and sensorimotor alignment effects. As regards response times, we found that in the imagination of rotation and physical rotation conditions the encoding alignment effect was higher than the sensorimotor alignment effect, while in the walking condition this gap disappeared. We interpreted these results in terms of an enhanced link between allocentric and sensorimotor representations, due to the information acquired through walking.     

Seeing Like a Geologist: Bayesian Use of Expert Categories in Location Memory

Memory for spatial location is typically biased, with errors trending toward the center of a surrounding region. According to the category adjustment model (CAM), this bias reflects the optimal, Bayesian combination of fine‐grained and categorical representations of a location. However, there is disagreement about whether categories are malleable. For instance, can categories be redefined based on expert‐level conceptual knowledge? Furthermore, if expert knowledge is used, does it dominate other information sources, or is it used adaptively so as to minimize overall error, as predicted by a Bayesian framework? We address these questions using images of geological interest. The participants were experts in structural geology, organic chemistry, or English literature. Our data indicate that expertise‐based categories influence estimates of location memory—particularly when these categories better constrain errors than alternative (“novice”) categories. Results are discussed with respect to the CAM.     

Working memory impairment in people with Williams syndrome: Effects of delay, task and stimuli

Williams syndrome (WS) is a neurodevelopmental disorder associated with impaired visuospatial representations subserved by the dorsal stream and relatively strong object recognition abilities subserved by the ventral stream. There is conflicting evidence on whether this uneven pattern in WS extends to working memory (WM). The present studies provide a new perspective, testing WM for a single stimulus using a delayed recognition paradigm in individuals with WS and typically developing children matched for mental age (MA matches). In three experiments, participants judged whether a second stimulus ‘matched’ an initial sample, either in location or identity. We first examined memory for faces, houses and locations using a 5 s delay (Experiment 1) and a 2 s delay (Experiment 2). We then tested memory for human faces, houses, cat faces, and shoes with a 2 s delay using a new set of stimuli that were better controlled for expression, hairline and orientation (Experiment 3). With the 5 s delay (Experiment 1), the WS group was impaired overall compared to MA matches. While participants with WS tended to perform more poorly than MA matches with the 2 s delay, they also exhibited an uneven profile compared to MA matches. Face recognition was relatively preserved in WS with friendly faces (Experiment 2) but not when the faces had a neutral expression and were less natural looking (Experiment 3). Experiment 3 indicated that memory for object identity was relatively stronger than memory for location in WS. These findings reveal an overall WM impairment in WS that can be overcome under some conditions. Abnormalities in the parietal lobe/dorsal stream in WS may damage not only the representation of spatial location but may also impact WM for visual stimuli more generally.     

Memory for time of training modulates performance on a place conditioning task in marmosets

In rodents, the expression of a reward-conditioned place preference (CPP) is regulated in a circadian pattern such that the preference is exhibited strongly at the circadian time of prior training but not at other circadian times. Because each animal is trained only at a single circadian phase, the concept of time as a context cue is derived from a rhythmic internal state rather than learned explicitly from the external cues. We now report that the same “time memory” is expressed following context conditioning in the common marmoset (Callithrix jacchus). Animals were trained at a specific time to discriminate between an unpaired context and a context paired with food reward. Marmosets were then tested for preference at circadian times that were either the same or different from the training time. Preference was expressed only when training and testing times matched. The results show that time of day learning can be generalized to this new world primate implying that a similar circadian mechanism might regulate craving for reward in diverse mammals including human beings.     

How the Learning Path and the Very Structure of a Multifloored Environment Influence Human Spatial Memory

Few studies have explored how humans memorize landmarks in complex multifloored buildings. They have observed that participants memorize an environment either by floors or by vertical columns, influenced by the learning path. However, the influence of the building’s actual structure is not yet known. In order to investigate this influence, we conducted an experiment using an object-in-place protocol in a cylindrical building to contrast with previous experiments which used rectilinear environments. Two groups of 15 participants were taken on a tour with a first person perspective through a virtual cylindrical three-floored building. They followed either a route discovering floors one at a time, or a route discovering columns (by simulated lifts across floors). They then underwent a series of trials, in which they viewed a camera movement reproducing either a segment of the learning path (familiar trials), or performing a shortcut relative to the learning trajectory (novel trials). We observed that regardless of the learning path, participants better memorized the building by floors, and only participants who had discovered the building by columns also memorized it by columns. This expands on previous results obtained in a rectilinear building, where the learning path favoured the memory of its horizontal and vertical layout. Taken together, these results suggest that both learning mode and an environment’s structure influence the spatial memory of complex multifloored buildings.     

Use of landmark features and geometry by children and adults during a two-dimensional search task

Three- to six-year-old children (n = 28) and adults (n = 46) participated in a two-dimensional search task that included geometry and feature conditions. During each of 24 trials, participants watched as a cartoon character hid behind one of three landmarks arranged in a triangle on a computer screen. The landmarks and character then disappeared and reappeared in the same or a new position on the screen. During feature condition trials participants could use unique features of the landmarks to locate the hidden character, while during geometry trials participants could only use the geometry of the triangle. In both conditions, adults’ performance was near ceiling while children’s performance was significantly worse. Children’s performance was worse in the geometry condition than in the feature condition but search accuracy improved with age for both types of information. Findings are considered in the context of the broader literature on spatial cognition and development.     

The effects of binge MDMA on acquisition and reversal learning in a radial-arm maze task

The current study used the partially-baited radial-arm maze paradigm to study the effects of a single-treatment high-dose exposure ('binge') to MDMA (± 3,4-methylenedioxymethaphemtamine or 'Ecstasy') on memory task acquisition. Sprague-Dawley rats were administered a binge dose (4 × 10 mg/kg) of MDMA and their ability to subsequently acquire the radial-arm maze task was compared against saline controls. The MDMA-treated rats were significantly slower to learn the task and made more reference memory errors than the controls. Working memory function was found to be relatively unimpaired. Following a reversal of task rules the MDMA-treated rats were again significantly slower to acquire the appropriate rule despite having eventually achieved a similar level of overall performance as control rats. However evidence of drug tolerance was found when all rats were challenged with an acute low dose of MDMA (1 × 4.0 mg/kg) because the binge MDMA rats were relatively less impaired. Therefore, although binge treated MDMA rats were able to achieve very accurate performance equivalent to the controls they took significantly longer to do this and were less able to adapt their behavior to a change in task rules. In addition the binge treated MDMA rats displayed tolerance to acute MDMA exposure. These findings are consistent with the possibility that human Ecstasy users may show deficits in acquiring information and may experience deficits in cognitive flexibility as well as developing tolerance to the drug with repeated exposure.     

编码任务对来源记忆的影响:一项事件相关电位研究

本研究采用ERPs技术,探讨编码任务对来源记忆的影响及其神经机制。在学习阶段,被试进行两种编码操作：匹配判断任务和大小判断任务;在测验阶段,让被试进行来源判断任务。行为结果发现：在编码阶段,匹配判断任务比大小判断任务需要更长的时间;在测验阶段,匹配判断任务在“项目旧/背景旧”和“部分旧”条件的正确率显著高于大小判断任务,匹配判断任务在“项目旧/背景旧”条件的反应时显著短于大小判断任务。测验阶段ERPs结果发现：两种编码任务的新旧效应在200~700ms均有较广泛的头皮分布,而在700~1100ms呈前额皮层最大化分布;匹配判断任务的新旧效应比大小判断任务更大,表现在600~700ms的FPz电极以及700~800ms的Pz、P4电极。由此可见,在来源记忆中,编码任务影响来源记忆,主要表现在后部顶区位置;晚期前额皮层新旧效应不受任务难度因素的影响。