Episodic Memory in Schizophrenia

Episodic memory impairments in individuals with schizophrenia have been well documented in the literature. However, despite the abundance of findings, constituent cognitive, neural, behavioral, and genetic components of the deficits continue to elude full characterization. This review provides a characterization of these deficits by organizing findings within three frameworks of interest: 1) neuroanatomical; 2) genetic; and 3) behavioral. Within each approach, evidence from imaging studies as well as behavioral studies is examined. The hope is that by synthesizing the cognitive science paradigms, molecular genetic neurophysiological findings, and computational algorithms applied to medial temporal lobe subregions, we will be able to expand our understanding of the types of compromises in episodic memory systems of individuals with schizophrenia.     

DNA

The authors predict that in a few years, many areas of psychology will be awash in specific genes responsible for the widespread influence of genetics on behavior. As the focus shifts from finding genes (genomics) to understanding how genes affect behavior (behavioral genomics), it is important for the future of psychology as a science that pathways between genes and behavior be examined not only at the molecular biological level of cells or the neuroscience level of the brain but also at the psychological level of analysis. After a brief overview of quantitative genetic research, the authors describe how genes that influence complex traits like behavioral dimensions and disorders in human and nonhuman animals are being found. Finally, the authors discuss behavioral genomics and predict that DNA will revolutionize psychological research and treatment early in the 21st century.     

Behavior Genetics: What's New? What's Next?

What's new in behavior genetics? With widespread acceptance that nearly all behavioral variation reflects some genetic influence, current studies are investigating developmental changes in the nature and magnitude of genetic and environmental effects, the extent to which different behaviors are influenced by common genes, and different forms of gene-environment correlation and interaction. New designs, focused on assessment of unrelated children in the same households or neighborhood environments, and use of measured environmental variables within genetically informative designs, are yielding more incisive evidence of common environmental effects on behavior. What will be next? Behavior genetic techniques and analyses will be used to inform efforts to find genes altering susceptibility for disorder and dispositional genes affecting behavioral variation. The developing integration of behavioral and molecular genetics will identify genes influencing specific behavioral variation and enhance understanding of how they do so. Psychologists will play a pivotal role in communicating that understanding to the public and in facilitating consideration of the inevitable ethical issues then to be confronted.     

Intelligence: genetics, genes, and genomics

More is known about the genetics of intelligence than about any other trait, behavioral or biological, which is selectively reviewed in this article. Two of the most interesting genetic findings are that heritability of intelligence increases throughout the life span and that the same genes affect diverse cognitive abilities. The most exciting direction for genetic research on intelligence is to harness the power of the Human Genome Project to identify some of the specific genes responsible for the heritability of intelligence. The next research direction will be functional genomics--for example, understanding the brain pathways between genes and intelligence. Deoxyribonucleic acid (DNA) will integrate life sciences research on intelligence; bottom-up molecular biological research will meet top-down psychological research in the brain.     

Mental retardation genes in drosophila: New approaches to understanding and treating developmental brain disorders

Drosophila melanogaster is emerging as a valuable genetic model system for the study of mental retardation (MR). MR genes are remarkably similar between humans and fruit flies. Cognitive behavioral assays can detect reductions in learning and memory in flies with mutations in MR genes. Neuroanatomical methods, including some at single-neuron resolution, are helping to reveal the cellular bases of faulty brain development caused by MR gene mutations. Drosophila fragile X mental retardation 1 (dfmr1) is the fly counterpart of the human gene whose malfunction causes fragile X syndrome. Research on the fly gene is leading the field in molecular mechanisms of the gene product's biological function and in pharmacological rescue of brain and behavioral phenotypes. Future work holds the promise of using genetic pathway analysis and primary neuronal culture methods in Drosophila as tools for drug discovery for a wide range of MR and related disorders.     

Validation of a rodent model of episodic memory

Episodic memory consists of representations of specific episodes that happened in the past. Modeling episodic memory in animals requires careful examination of alternative explanations of performance. Putative evidence of episodic-like memory may be based on encoding failure or expectations derived from well-learned semantic rules. In Experiment 1, rats were tested in a radial maze with study and test phases separated by a retention interval. The replenishment of chocolate (at its study-phase location) depended on two factors: time of day (morning vs. afternoon) and the presence or absence of chocolate pellets at the start of the test phase. Because replenishment could not be decoded until the test phase, rats were required to encode the study episode. Success in this task rules out encoding failure. In Experiment 2, two identical mazes in different rooms were used. Chocolate replenishment was trained in one room, and then they were asked to report about a recent event in a different room, where they had no expectation that the memory assessment would occur. Rats successfully answered the unexpected question, ruling out use of expectations derived from well-learned semantic rules. Our behavioral methods for modeling episodic memory may have broad application for assessments of genetic, neuroanatomical, neurochemical, and neurophysiological bases of both episodic memory and memory disorders such as those that occur in Alzheimer’s disease.     

Behavioral and genetic characterization of habituation using Caenorhabditis elegans

This review surveys the literature that investigates the behavioral characterization and cellular and molecular mechanisms of habituation using the model organism Caenorhabditis elegans. In 1990, C. elegans was first observed to show habituation to a non-localized mechanical tap. The parameters that govern this behavioral plasticity in C. elegans were subsequently characterized, which lead to the important hypothesis that habituation is mediated by multiple mechanisms. Many tools are available to C. elegans researchers that allow for relatively easy genetic manipulation. This has lead to a number of recent genetic studies that have begun to identify key genes and molecules that play a role in the mechanisms of habituation. Some of these genes include a vesicular glutamate transporter, a glutamate receptor subunit, a dopamine receptor and downstream intracellular signaling molecules, such as G proteins and kinases. Some of these genes only affect certain parameters of habituation, but not others supporting the hypothesis that multiple mechanisms mediate habituation. The field of research has also led to the dissection of different phases of memory (short-term vs. long-term memory for habituation), which are triggered by different training paradigms. The differences in mechanism between these various forms of memory are also beginning to be revealed.     

Cognitive neuroscience of episodic memory encoding

This paper presents a cognitive neuroscientific perspective on how human episodic memories are formed. Convergent evidence from multiple brain imaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) suggests a role for frontal cortex in episodic memory encoding. Activity levels within frontal cortex can predict episodic memory encoding across a wide range of behavioral manipulations known to influence memory performance, such as those present during levels of processing and divided attention manipulations. Activity levels within specific frontal and medial temporal regions can even predict, on an item by item basis, whether an episodic memory is likely to form. Furthermore, separate frontal regions appear to participate in supplying code-specific information, including distinct regions which process semantic attributes of verbal information as well as right-lateralized regions which process nonverbal information. We hypothesize that activity within these multiple frontal regions provides a functional influence (input) to medical temporal regions that bind the information together into a lasting episodic memory trace.     

Where perception meets memory: A review of repetition priming in visual search tasks

What we have recently seen and attended to strongly influences how we subsequently allocate visual attention. A clear example is how repeated presentation of an object’s features or location in visual search tasks facilitates subsequent detection or identification of that item, a phenomenon known as priming. Here, we review a large body of results from priming studies that suggest that a short-term implicit memory system guides our attention to recently viewed items. The nature of this memory system and the processing level at which visual priming occurs are still debated. Priming might be due to activity modulations of low-level areas coding simple stimulus characteristics or to higher level episodic memory representations of whole objects or visual scenes. Indeed, recent evidence indicates that only minor changes to the stimuli used in priming studies may alter the processing level at which priming occurs. We also review recent behavioral, neuropsychological, and neurophysiological evidence that indicates that the priming patterns are reflected in activity modulations at multiple sites along the visual pathways. We furthermore suggest that studies of priming in visual search may potentially shed important light on the nature of cortical visual representations. Our conclusion is that priming occurs at many different levels of the perceptual hierarchy, reflecting activity modulations ranging from lower to higher levels, depending on the stimulus, task, and context—in fact, the neural loci that are involved in the analysis of the stimuli for which priming effects are seen.     

Behavioral specifications of reward-associated long-term memory enhancement in humans

Recent functional imaging studies link reward-related activation of the midbrain substantia nigra-ventral tegmental area (SN/VTA), the site of origin of ascending dopaminergic projections, with improved long-term episodic memory. Here, we investigated in two behavioral experiments how (1) the contingency between item properties and reward, (2) the magnitude of reward, (3) the uncertainty of outcomes, and (4) the contextual availability of reward affect long-term memory. We show that episodic memory is enhanced only when rewards are specifically predicted by the semantic identity of the stimuli and changes nonlinearly with increasing reward magnitude. These effects are specific to reward and do not occur in relation to outcome uncertainty alone. These behavioral specifications are relevant for the functional interpretation of how reward-related activation of the SN/VTA, and more generally dopaminergic neuromodulation, contribute to long-term memory.     

对人类不良记忆的修饰：来自记忆再巩固的证据

已经巩固的长时记忆被再次提取后, 进入一个记忆的不稳定期, 在此过程中, 记忆可被更新、强化、削弱甚至抹除, 这个过程称为再巩固。人类不良记忆再巩固研究揭示记忆激活后口服普萘洛尔(propranolol)或进行消退训练可削弱或抹除不良情绪记忆, 此过程中涉及杏仁核、海马、前额叶皮层等脑区的参与及其构成的神经环路的调控。当前临床上利用再巩固原理可通过药物治疗、行为干预或无创脑部刺激的方法改变不良记忆。然而, 由于其形成过程复杂并受多种因素影响, 未来研究应尽可能模拟临床中人类不良记忆形成的复杂环境, 深入探讨再巩固“边界问题”, 推动实验室研究向临床应用的转化。     

NMDA signaling in CA1 mediates selectively the spatial component of episodic memory

Recent studies focusing on the memory for temporal order have reported that CA1 plays a critical role in the memory for the sequences of events, in addition to its well-described role in spatial navigation. In contrast, CA3 was found to principally contribute to the memory for the association of items with spatial or contextual information in tasks focusing on spatial memory. Other studies have shown that NMDA signaling in the hippocampus is critical to memory performance in studies that have investigated spatial and temporal order memory independently. However, the role of NMDA signaling separately in CA1 and CA3 in memory that combines both spatial and temporal processing demands (episodic memory) has not been examined. Here we investigated the effect of the deletion of the NR1 subunit of the NMDA receptor in CA1 or CA3 on the spatial and the temporal aspects of episodic memory, using a behavioral task that allows for these two aspects of memory to be evaluated distinctly within the same task. Under these conditions, NMDA signaling in CA1 specifically contributes to the spatial aspect of memory function and is not required to support the memory for temporal order of events.     

Bridging the gap between brain and behavior: cognitive and neural mechanisms of episodic memory

The notion that non-human animals are capable of episodic memory is highly controversial. Here, we review recent behavioral work from our laboratory showing that the fundamental features of episodic memory can be observed in rats and that, as in humans, this capacity relies on the hippocampus. We also discuss electrophysiological evidence, from our laboratory and that of others, pointing to associative and sequential coding in hippocampal cells as potential neural mechanisms underlying episodic memory.     

The Effects of Healthy Aging,Amnestic Mild Cognitive Impairment,and Alzheimer’s Disease on Recollection and Familiarity: A Meta-Analytic Review

It is well established that healthy aging, amnestic Mild Cognitive Impairment (aMCI), and Alzheimer’s Disease (AD) are associated with substantial declines in episodic memory. However, there is still debate as to how two forms of episodic memory – recollection and familiarity – are affected by healthy and pathological aging. To address this issue we conducted a meta-analytic review of the effect sizes reported in studies using remember/know (RK), receiver operating characteristic (ROC) and process dissociation (PD) methods to examine recollection and familiarity in healthy aging (25 published reports), aMCI (9 published reports), and AD (5 published reports). The results from the meta-analysis revealed that healthy aging is associated with moderate-to-large recollection impairments. Familiarity was not impaired in studies using ROC or PD methods but was impaired in studies that used the RK procedure. aMCI was associated with large decreases in recollection whereas familiarity only tended to show a decrease in studies with a patient sample comprised of both single-domain and multiple-domain aMCI patients. Lastly, AD was associated with large decreases in both recollection and familiarity. The results are consistent with neuroimaging evidence suggesting that the hippocampus is critical for recollection whereas familiarity is dependent on the integrity of the surrounding perirhinal cortex. Moreover, the results highlight the relevance of method selection when examining aging, and suggest that familiarity deficits might be a useful behavioral marker for identifying individuals that will develop dementia.     

Are Episodic Buffer Processes Intact in ADHD? Experimental Evidence and Linkage with Hyperactive Behavior

Working memory deficits are present in a substantial proportion of children with ADHD, and converging evidence links these deficits with ADHD-related behavioral and functional impairments. At the same time, working memory is not a unitary construct, and evidence is lacking regarding the role of several components of this system in ADHD. Preclinical behavioral studies are needed to fractionate the multicomponent working memory system, determine which specific subcomponent(s) are impaired in ADHD, and more importantly link these subcomponent(s) with specific ADHD-related behavioral symptoms/functional impairments. The current study reflects one piece of that puzzle, and focuses on the episodic buffer component of working memory. Across multiple testing days, a well-characterized sample of 86 children ages 8–13 (M=10.52, SD=1.54; 34 girls; 64% Caucasian/Non-Hispanic) with ADHD (n=49) and without ADHD (n=37) completed three counterbalanced working memory tests that were identical in all aspects except the key subcomponent process (phonological, visuospatial, episodic buffer). Gross motor movement during these and control tasks were measured using 4 high-precision actigraphs. There was no evidence of group differences in gender, age, SES, or IQ. Bayesian mixed-model ANOVAs indicated that the ADHD group performed significantly worse on all three working memory tests (d=1.17–1.44) and was significantly more hyperactive than controls (d=0.66–1.05) during the visuospatial and episodic buffer tests. In contrast, the ADHD and Non-ADHD groups were equivalent with regard to effects of episodic buffer demands on performance and hyperactive behavior. The most parsimonious conclusion is that the episodic buffer is likely intact in ADHD, and unrelated to ADHD hyperactivity symptoms.     

The relationship between autobiographical memory,cognition, and emotion in older adults: a review

Over the past 30 years, the concept of “autobiographical memory” has been highlighted in numerous behavioral and neuroanatomical studies. Importantly, episodic autobiographical memory, an aspect of autobiographical memory, has been shown to decrease with age but can be improved by training. Autobiographical memory is deeply associated with the default mode network (especially posterior cingulate cortex and medial prefrontal cortex), which is particularly interesting in the context of better understanding the relationship between autobiographical memory, cognition, and emotion in older adults. This article provides an overview of the behavioral and neuroanatomical characteristics of autobiographical memory, as well as its relationship with the default mode network, cognition, emotion, and aging. This article also provides an overall review of autobiographical memory training.     

Behavioral and molecular genetic contributions to a dimensional classification of personality disorder

This article examines the possible contribution of behavioral and molecular genetic research to the development of a dimensional classification of personality disorder. It is argued that the results of molecular studies are too preliminary to have immediate nosological significance. However, behavioral genetic methods could play a useful role in constructing a classification that reflects the genetic architecture of personality disorder. It is also argued that the best approach to constructing a valid classification would be to integrate behavioral genetic methods with the construct validation framework used in test construction. An integrative approach is proposed that seeks to combine constructs from alternative dimensional models. It is suggested that strong evidence of a four-dimensional structure to personality disorder provides a way to organize a preliminary model. An initial set of primary traits to define these secondary domains would then be compiled from existing models and refined using a combination of traditional psychometric analyses and behavioral genetic methods. It is concluded that an etiologically based classification is feasible for the DSM-V.     

The neuroanatomy and neuroendocrinology of fragile X syndrome

Fragile X syndrome (FXS), caused by a single gene mutation on the X chromosome, offers a unique opportunity for investigation of gene-brain-behavior relationships. Recent advances in molecular genetics, human brain imaging, and behavioral studies have started to unravel the complex pathways leading to the cognitive, psychiatric, and physical features that are unique to this syndrome. In this article, we summarize studies focused on the neuroanatomy and neuroendocrinology of FXS. A review of structural imaging studies of individuals with the full mutation shows that several brain regions are enlarged, including the hippocampus, amygdala, caudate nucleus, and thalamus, even after controlling for overall brain volume. These regions mediate several cognitive and behavioral functions known to be aberrant in FXS such as memory and learning, information and sensory processing, and social and emotional behavior. Two regions, the cerebellar vermis, important for a variety of cognitive tasks and regulation of motor behavior, and the superior temporal gyrus, involved in processing complex auditory stimuli, are reported to be reduced in size relative to controls. Functional imaging, typically limited to females, has emphasized that individuals with FXS do not adequately recruit brain regions that are normally utilized by unaffected individuals to carry out various cognitive tasks, such as arithmetic processing or visual memory tasks. Finally, we review a number of neuroendocrine studies implicating hypothalamic dysfunction in FXS, including abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis. These studies may help to explain the abnormal stress responses, sleep abnormalities, and physical growth patterns commonly seen in affected individuals. In the future, innovative longitudinal studies to investigate development of neurobiologic and behavioral features over time, and ultimately empirical testing of pharmacological, behavioral, and even molecular genetic interventions using MRI are likely to yield significant positive changes in the lives of persons with FXS, as well as increase our understanding of the development of psychiatric and learning problems in the general population.     

IMPLICIT AND EXPLICIT MEMORY FOR HAPTICALLY EXPERIENCED TWO-DIMENSIONAL PATTERNS

Abstract— Recent research with visual objects has delineated important representational differences between memory measures that tap identification (implicit tests) and measures that require episodic recognition (explicit tests). We investigated whether these differences reflect a fundamental architecture for the representation of object information in memory. In the present experiment, we contrasted identification and episodic recognition for haptically presented two-dimensional patterns. Haptic identification was not affected by elaborative processing at study, whereas haptic episodic recognition was enhanced by elaborative processing. This finding suggests important similarities in the organization of object information in the visual and haptic modalities.     

Episodic recollection in animals: “If it walks like a duck and quacks like a duck…”

In humans, episodic memory is most commonly defined as the subjective experience of recollection, presenting a major challenge to the identification of episodic memory in animals. Here we take the position that episodic memory also has several other distinctive qualities that can be assessed objectively in animals, as well as humans, and the examination of these properties provides insights into underlying mechanisms of episodic memory. We focus on recent evidence accumulated in this laboratory indicating that recognition in rats involves a threshold retrieval process, similar to that observed in human episodic recall. Also, rats can remember the temporal order of unique events, characteristic of the replay of vivid episodic memories in humans. Furthermore, rats combine elements of “when” and “where” events occur, as well as the flow of events within a memory, to distinguish memories that share overlapping features, also characteristic of human episodic memory. Finally, all of these capacities are dependent on the hippocampus, which also plays a critical role in human episodic memory. This combination of findings strongly suggests that animals have the same fundamental information processing functions that underlie episodic recall in humans.