The biochemistry of memory: The 26year journey of a 'new and specific hypothesis'

This Special Issue of Neurobiology of Learning and Memory dedicated to Dr. Richard Thompson to celebrate his 80th birthday and his numerous contributions to the field of learning and memory gave us the opportunity to revisit the hypothesis we proposed more than 25years ago regarding the biochemistry of learning and memory. This review summarizes our early 1980s hypothesis and then describes how it was tested and modified over the years following its introduction. We then discuss the current status of the hypothesis and provide some examples of how it has led to unexpected insights into the memory problems that accompany a broad range of neuropsychiatric disorders.     

Rapid learning in attention shifts: A review

Many lines of evidence show that the human visual system does not simply passively register whatever appears in the visual field. The visual system seems to preferentially “choose” stimuli according to what is most relevant for the task at hand, a process called attentional selection. Given the large amount of information in any given visual scene, and well-documented capacity limitations for the representation of visual stimuli, such a strategy seems only reasonable. Consistent with this, human observers are surprisingly insensitive to large changes in their visual environment when they attend to something else in the visual scene. Here I argue that attentional selection of pertinent information is heavily influenced by the stimuli most recently viewed that were important for behaviour. I will describe recent evidence for the existence of a powerful memory system, not under any form of voluntary control, which aids observers in orienting quickly and effectively to behaviourally relevant stimuli in the visual environment, in particular the stimuli that have been important in the immediate past. I will also discuss research into the potential neural mechanisms involved in these learning effects. Finally, I will discuss how these putative memory mechanisms may help in maintaining the apparent stability and continuity of the ever-changing visual environment, which is such a crucial component of our everyday visual experience.     

Category learning and multiple memory systems

Categorization is a vitally important skill that people use every day. Early theories of category learning assumed a single learning system, but recent evidence suggests that human category learning may depend on many of the major memory systems that have been hypothesized by memory researchers. As different memory systems flourish under different conditions, an understanding of how categorization uses available memory systems will improve our understanding of a basic human skill, lead to better insights into the cognitive changes that result from a variety of neurological disorders, and suggest improvements in training procedures for complex categorization tasks.     

Autobiographical Memory, Self, and Stress-Related Psychiatric Disorders: Which Implications in Cancer Patients?

Autobiographical memory refers to information and memories of personal life events, accumulated since childhood, which enable the construction of a feeling of identity and continuity. Autobiographical memory retrieval is a dynamic and reconstructive process, as mental representations change with the passage of time. This flexible aspect of memory is linked to one’s changing self and aspirations over time, that evolve according to our personal status and environment. Hence, any breakdown in the continuity of life involves a distortion of memory. Such distortions can be observed in stress-related psychiatric disorders, such as major depression or post-traumatic stress disorder, where autobiographical memory retrieval is characterized by overgenerality (i.e., the tendency to recall generic memories rather than specific events in response to cue words). Such memory disorders can be observed at different degrees in cancer patients. We will report studies focusing on the above-mentioned psychiatric disorders and cancer, and will attempt to establish a relation with autobiographical memory disturbances. The better understanding of such memory deficits could permit new pathophysiological hypotheses to emerge. Recommendations for future research that will enhance understanding of the factors that contribute to autobiographical memory in cancer are suggested.     

Perspectives and problems in motor learning

Movement provides the only means we have to interact with both the world and other people. Such interactions can be hard-wired or learned through experience with the environment. Learning allows us to adapt to a changing physical environment as well as to novel conventions developed by society. Here we review motor learning from a computational perspective, exploring the need for motor learning, what is learned and how it is represented, and the mechanisms of learning. We relate these computational issues to empirical studies on motor learning in humans.     

What memory is for

Let's start from scratch in thinking about what memory is for, and consequently, how it works. Suppose that memory and conceptualization work in the service of perception and action. In this case, conceptualization is the encoding of patterns of possible physical interaction with a three-dimensional world. These patterns are constrained by the structure of the environment, the structure of our bodies, and memory. Thus, how we perceive and conceive of the environment is determined by the types of bodies we have. Such a memory would not have associations. Instead, how concepts become related (and what it means to be related) is determined by how separate patterns of actions can be combined given the constraints of our bodies. I call this combination "mesh." To avoid hallucination, conceptualization would normally be driven by the environment, and patterns of action from memory would play a supporting, but automatic, role. A significant human skill is learning to suppress the overriding contribution of the environment to conceptualization, thereby allowing memory to guide conceptualization. The effort used in suppressing input from the environment pays off by allowing prediction, recollective memory, and language comprehension. I review theoretical work in cognitive science and empirical work in memory and language comprehension that suggest that it may be possible to investigate connections between topics as disparate as infantile amnesia and mental-model theory.     

催产素对学习和记忆的调节效应：来自动物与人类的研究证据

作为一种神经肽, 催产素对于个体社会认知和情绪加工有着非常重要的调节作用, 其中就包括对在人们工作和生活中扮演着关键角色的学习和记忆活动的影响。采用不同模态技术的动物和人类研究一致表明了外源性催产素对于学习和记忆具有重要的调节作用, 这一作用可能是外源性催产素通过与多巴胺奖赏通路、边缘系统等学习和记忆关键脑网络中广泛分布的催产素受体相结合, 进而调整其功能状态实现的; 但与此同时, 催产素对学习和记忆的促进或抑制作用会因实验范式、刺激材料、给药时间、位置和剂量等因素的不同而存在差异。未来需要协同动物和人类研究的各自优势, 采用规范化的实验任务设置和给药程序克服当前该领域的研究局限, 并积极发掘催产素在干预相关精神疾病患者学习和记忆加工缺陷中的应用潜力。     

Fischer 344 and wistar rats differ in anxiety and habituation but not in water maze performance

The fact that various neuropharmacological substances have anxiolytic as well as amnesic effects suggests that neuronal mechanisms of anxiety and learning/memory closely interact. Hence, we hypothesized that differences in anxiety-related behavior could be accompanied with differences in cognition or habituation. Two rat strains with different levels of anxiety, more anxious Fischer 344 rats by Charles River (FC) and less anxious Wistar rats by Winkelmann (WW), were tested in the Morris water maze task and an open field test for habituation learning. Additionally, we investigated the effect of different light intensities on the performance in the Morris water maze and the elevated plus maze. The results of the water maze task indicate that differences in anxiety-related behavior do not go along with differences in this performance of learning/memory. Moreover, the test was not affected by different light intensities. In contrast, illumination did affect performance in the elevated plus maze test, wherein dim light provoked an anxiolytic effect in both rat strains. The findings that neither different baseline levels of anxiety nor fear modulating light conditions were accompanied by changes in the performance of rats in the Morris water maze led us to the suggestion that there is no connection between anxiety and learning/memory in this task. Contrarily, anxiety might be associated with habituation learning in the open field test, shown by the superior habituation of the anxious FC rats in comparison to the less anxious WW rats. In sum, these results indicate that anxiety and learning/memory seem to be independently regulated behaviors, whereas habituation might be more closely correlated with anxiety. Nevertheless, a general statement about the relation between emotionality and learning/memory mechanisms would be premature and the link between behaviors remains to be clarified.     

Bio-inspired cognitive architecture of episodic memory

Memory and learning are essential functions in human beings as they allow us to acquire and store in the brain representations of thoughts, experiences, and behaviors, which are required for problem-solving in our daily life and mainly for survival. Episodic memory is a type of memory that provides the ability to re-experience events in one’s life, and it is associated with their conscious recollection. Since episodic memory can represent our experiences about the environment, similar to a mental journey, it is desired in systems that attempt to create human-like behavior. Currently, the main problem is that state of the art proposals do not consider neuroscientific evidence like memory dynamics for forgetting or bottom-up inputs, and most of them do not consider episodic memory as a different memory but as part of general declarative memory. We consider these omissions to limit the generation of human-like behavior. In this work, we propose a bio-inspired cognitive architecture of episodic memory. Neuroscientific evidence provides us with the brain structures associated with this type of memory, the connections, and the operations these areas perform. We hypothesize that virtual entities endowed with our episodic memory cognitive architecture will plan and make decisions in a more human-like fashion. To test the capabilities of the proposal, we endowed a virtual creature with a distributed and concurrent implementation of our architecture, and it was given two tasks. The first task validated the functions of the memory independently, and in the second task, the creature used episodic memory to solve a planning problem. From the results of these experiments, we validate our proposal and show that it is possible to create a system that behaves as the human brain does.     

There is no such thing as environmental ethics

Engineers and scientists, whose professional responsibilities often influence the natural environment, have sought to develop an environmental ethic that will be in tune with their attitudes toward the non-human environment, and that will assist them in decision making regarding questions of environmental quality. In this paper the classical traditions in normative ethics are explored in an attempt to formulate such an environmental ethic. I conclude, however, that because the discipline of ethics is directed at person-person interactions, ethics as a scholarly discipline does not help us understand how we ought to treat non-human nature. We therefore cannot look to ethics as a source for understanding our attitudes and for providing guidance to our actions with regard to the environment. To do so is to ask too much of ethics. If we are to find an acceptable environmental morality, it must come from a new paradigm. One approach might be to understand our attitudes on the basis of spirituality, modeled after animistic religions.     

A critique of the neuroecology of learning and memory

Recent years have seen the emergence of neuroecology, the study of the neural mechanisms of behaviour guided by functional and evolutionary principles. This research has been of enormous value for our understanding of the evolution of brain- and species-specific behaviour. However, we question the validity of the neuroecological approach when applied to the analysis of learning and memory, given its arbitrary assumption that different ‘problems’ engage different memory mechanisms. Differences in memory-based performance in ‘natural’ tasks do not prove differences in memory capacity; similarly, differences in the use of memory in the natural environment do not provide a sound basis for expecting differences in anatomical structures that subserve learning and memory. This critique is illustrated with examples taken from the study of the neurobiology of food storing and song learning in birds.     

Taste perceptual circuit for the generation of autonomous responses in virtual creatures

BraLearning is one of the most complex cognitive processes that living beings have. This process is distributed within the brain and each independent cognitive function contributes to a small or large extent to it. Particularly, affective learning is a process that allows us to identify stimuli in the environment and discriminate them based on our tastes or preferences. Within this work we will address a type of affective evaluation generated by the perceptual circuit of taste that allows us to determine flavors from the environment and how this information becomes part of the perceptual affective evaluation. We will start this work by identifying other computational works that address affective processes oriented to taste or that involve some other affective evaluation. Subsequently, we analyze of neuroscientific information that allows us to build an informal model of the perceptual circuit of taste. Finally, we propose a cognitive architecture for the generation of autonomous responses oriented to taste in virtual creatures and we will demonstrate its functionality through an implementation of this model in some case studies through distributed modules and discuss the results obtained.     

In search of the neurobiological underpinnings of the differential outcomes effect

Correlating unique rewards with to-be-remembered events (the Differential Outcomes Procedure [DOP]) enhances learning and memory performance in a range of species. Recently, we have demonstrated that the DOP can be used to reduce or eliminate the learning and memory impairments associated with animal models of amnesia and dementia. This powerful phenomenon, the Differential Outcomes Effect (DOE), has led to the question: How does such a simple manipulation exert such dramatic influence on learning and memory performance? A revised two-process account of the DOE states that using the DOP results in the activation of reward expectancies through Pavlovian mechanisms. The use of unique reward expectancies alters the nature of cognitive processing used to solve discrimination tasks. The change in cognitive processing is represented by utilization of a different memory system than that commonly used to acquire and remenber information when a Nondifferential Outcomes Procedure (NOP) is used. Using neurochemical manipulations, it has been demonstrated that different, potentially independent, brain systems modulate memory performance when subjects are trained with a NOP versus a DOP. This memory-based DOP/NOP distinction resembles other dissociative memory theories in which two psychological processes are purportedly served by distinct neurobiological mechanisms. In addition, such results have important ramifications for the treatment of memory disorders because they demonstrate that stimulus and behavioral manipulations, like drugs, can influence neurotransmitter functioning.     

注意和记忆对孤独症儿童词汇发展滞后的影响

孤独症语言障碍的表现之一是词汇发展滞后, 可能与其注意和记忆损伤有关。当前研究结果表明, 孤独症儿童在学习词汇时难以利用社会注意提供的有效信息, 且其注意易受到无关刺激干扰, 这可能导致其形成的物体-词汇的联结不稳定, 影响其进一步将这种联结整合到心理词典并保存在记忆中。未来研究应探究联合注意影响孤独症儿童词汇学习的发展轨迹和机制, 儿童的词汇知识对其词汇记忆的影响, 并关注自然场景中孤独症儿童的词汇学习过程和个体差异。     

In Search of the Neurobiological Underpinnings of the Differential Outcomes Effect

Correlating unique rewards with to-be-remembered events (the Differential Outcomes Procedure [DOP]) enhances learning and memory performance in a range of species. Recently, we have demonstrated that the DOP can be used to reduce or eliminate the learning and memory impairments associated with animal models of amnesia and dementia. This powerful phenomenon, the Differential Outcomes Effect (DOE), has led to the question: How does such a simple manipulation exert such dramatic influence on learning and memory performance? A revised two-process account of the DOE states that using the DOP results in the activation of reward expectancies through Pavlovian mechanisms. The use of unique reward expectancies alters the nature of cognitive processing used to solve discrimination tasks. The change in cognitive processing is represented by utilization of a different memory system than that commonly used to acquire and remember information when a Nondifferential Outcomes Procedure (NOP) is used. Using neurochemical manipulations, it has been demonstrated that different, potentially independent, brain systems modulate memory performance when subjects are trained with a NOP versus a DOP. This memory-based DOP/NOP distinction resembles other dissociative memory theories in which two psychological processes are purportedly served by distinct neurobiological mechanisms. In addition, such results have important ramifications for the treatment of memory disorders because they demonstrate that stimulus and behavioral manipulations, like drugs, can influence neurotransmitter functioning.     

When increasing distraction helps learning: Distractor number and content interact in their effects on memory

Previous work has demonstrated that increasing the number of distractors in a search array can reduce interference from distractor content during target processing. However, it is unclear how this reduced interference influences learning of target information. Here, we investigated how varying the amount and content of distraction present in a learning environment affects visual search and subsequent memory for target items. In two experiments, we demonstrate that the number and content of competing distractors interact in their influence on target selection and memory. Specifically, while increasing the number of distractors present in a search array made target detection more effortful, it did not impair learning and memory for target content. Instead, when the distractors contained category information that conflicted with the target, increasing the number of distractors from one to three actually benefitted learning and memory. These data suggest that increasing numbers of distractors may reduce interference from conflicting conceptual information during encoding.