Eyeblink conditioning and systems consolidation: an ironic yet powerful pairing

Systems consolidation involves a prolonged process of memory reorganization that appears to be distinctly related to declarative memory. Declarative memory can be sharply contrasted with simple delay eyeblink classical conditioning, a prototypical example of nondeclarative memory. Yet inserting a trace interval between the conditioned and unconditioned stimuli endows eyeblink (trace) conditioning with many features of declarative memory. Work in humans has established that trace conditioning requires declarative memory. Recently trace eyeblink conditioning in animals has become one of the most powerful methods to study systems consolidation. Thus, it is ironic that a substantially nondeclarative form of memory has been so instructive concerning the organization of declarative memory.     

A ten-year longitudinal examination of repetition priming, incidental recall, free recall, and recognition in young and elderly

The effects of age and time on nondeclarative and declarative memory in young and elderly were examined in a 10-year longitudinal study using tests of word-stem priming, incidental recall, free recall, and recognition. The elderly were significantly impaired on all tests, but no reliable longitudinal decrement by the elderly was detected for priming, incidental recall,or recognition. The elderly demonstrated a significant longitudinal decline in declarative memory as assessed by a test of free recall. While nondeclarative memory declines with age, the longitudinal findings are consistent with the view that declarative memory is more susceptible to the effects of aging.     

Artificial grammar learning in Alzheimer’s disease

Patients with early Alzheimer’s disease (AD) exhibit impaired declarative memory although some forms of nondeclarative memory are intact. Performance on perceptual nondeclarative memory tasks is often preserved in AD, whereas conceptual nondeclarative memory is often impaired. A conceptual nondeclarative learning task that has been studied in amnesic patients is the artificial grammar learning (AGL) task. Healthy participants and patients with impaired declarative memory both acquire information about an underlying rule structure in this task and exhibit the ability to identify rule-conforming items, despite the subjective experience of guessing at the response. In this study, 12 patients diagnosed with early AD were tested on the AGL task and a matched recognition task. The patients were able to reliably distinguish rule-conforming items from others, indicating successful AGL. Performance of the AD patients was impaired, relative to controls, on a similar recognition task, although they were found to use information about the grammaticality of study items in an attempt to improve their recognition performance. The AD patients showed a dissociation similar to that seen in anterograde amnesia: impaired recognition memory in conjunction with successful AGL. This finding suggests that the brain areas that support AGL are not compromised early in the course of AD. In addition, the nondeclarative memory of the AD patients acquired during AGL appeared to influence their performance on a declarative memory task, suggesting an interaction between this nondeclarative memory task and declarative memory.     

Intact conceptual priming in the absence of declarative memory

Priming is an unconscious (nondeclarative) form of memory whereby identification or production of an item is improved by an earlier encounter. It has been proposed that declarative memory and priming might be related-for example, that conceptual priming results in more fluent processing, thereby providing a basis for familiarity judgments. In two experiments, we assessed conceptual priming and recognition memory across a 5-min interval in 5 memory-impaired patients. All patients exhibited fully intact priming in tests of both free association (study tent; at test, provide an association to canvas) and category verification (study lemon; at test, decide: Is lemon a type of fruit?). Yet the 2 most severely amnesic patients performed at chance on matched tests of recognition memory. These findings count against the notion that conceptual priming provides feelings of familiarity that can support accurate recognition judgments. We suggest that priming is inaccessible to conscious awareness and does not influence declarative memory.     

The anatomy of amnesia: neurohistological analysis of three new cases

The most useful information about the anatomy of human memory comes from cases where there has been extensive neuropsychological testing followed by detailed post-mortem neurohistological analysis. To our knowledge, only eight such cases have been reported (four with medial temporal lobe damage and four with diencephalic damage). Here we present neuropsychological and post-mortem neurohistological findings for one patient (NC) with bilateral damage to the medial temporal lobe and two patients (MG, PN) with diencephalic damage due to bilateral thalamic infarction and Korsakoff's syndrome, respectively. All three patients exhibited a similar phenotype of amnesia with markedly impaired declarative memory (anterograde and retrograde) but normal performance on tests of nondeclarative memory (e.g., priming and adaptation-level effects) as well as on tests of other cognitive functions. Patient NC had damage to the hippocampus (dentate gyrus and the CA1 and CA3 fields) and layer III of the entorhinal cortex, but with relative sparing of the CA2 field and the subiculum. Patient MG had damage to the internal medullary lamina and mediodorsal thalamic nuclei. Patient PN had damage to the mammillary nuclei, mammillothalamic tracts, and the anterior thalamic nuclei. These findings illuminate several issues regarding the relation between diencephalic and medial temporal lobe amnesia, the status of recognition memory in amnesia, and the neuroanatomy of memory.     

An examination of the effects of 5-Methoxy-n, n-di(ISO)propyltryptamine hydrochloride (Foxy) on cognitive development in rats

The hallucinogenic "designer drug" known as Foxy or Methoxy Foxy and formally know as 5-Methoxy-N,N-di(iso)propyltryptamine hydrochloride (5-MeO-DIPT) is rapidly gaining popularity among recreational users. However, little is known about the consequences of its use on neuropsychological development or behavior. During one of two adolescent periods, the rats were given repeated injections of either saline or 5 mg/kg of 5-MeO-DIPT. Once the animals reached 80 days of age, they were trained and tested on a number of tasks designed to assess the effects of 5-MeO-DIPT, if any, on memory tasks with spatial components that presumably involve declarative memory systems and on a nonspatial task that is considered sensitive to disruptions in nondeclarative memory. With one exception, both the 5-MeO-DIPT- and saline-treated rats were able to master the spatial navigation tests at comparable rates. However, the performance of the drug-treated rats was markedly inferior to that of the control animals on a response-learning task, suggesting a lack of flexibility in adapting their responses to changing task demands. This could indicate reductions in serotonin activity in the forebrain similar to the effects of studied drugs such as methylenedioxymethamphetamine (MDMA), suggesting 5-MeO-DIPT may act as a toxin compromising serotoninergic systems in the brain.     

Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans.

This article considers the role of the hippocampus in memory function. A central thesis is that work with rats, monkeys, and humans--which has sometimes seemed to proceed independently in 3 separate literatures--is now largely in agreement about the function of the hippocampus and related structures. A biological perspective is presented, which proposes multiple memory systems with different functions and distinct anatomical organizations. The hippocampus (together with anatomically related structures) is essential for a specific kind of memory, here termed declarative memory (similar terms include explicit and relational). Declarative memory is contrasted with a heterogeneous collection of nondeclarative (implicit) memory abilities that do not require the hippocampus (skills and habits, simple conditioning, and the phenomenon of priming). The hippocampus is needed temporarily to bind together distributed sites in neocortex that together represent a whole memory.     

Long-term follow-up of a childhood amnesic syndrome

In attempting to explain observed dissociations between impaired and preserved memory functioning in amnesia, various dichotomous memory systems (e.g., procedural versus declarative, episodic versus semantic, working versus reference memory) have often been employed. In such cases, the assumption has been that memory subserved by one system is preserved, while that of the other system is impaired. Cohen and Squire have suggested that in amnesia, declarative memory is impaired, although procedural memory is preserved. Long-term follow-up of a densely amnesic patient refutes this view by demonstrating significant anterograde learning of school subjects including reading, vocabulary, spelling, and arithmetic, all of which include some component of declarative memory. It appears that the procedural/declarative dichotomy is not adequate to explain preserved memory in amnesia.     

Declarativeand nondeclarativememory in opposition:When priorevents influence amnesicpatients morethan normal subjects

Amnesic patients and normal subjects read the names of nonfamous persons. Then, after being told that all the names were nonfamous, subjects judged the fame of names on a mixed list of new famous names, old nonfamous names, and new nonfamous names. Finally, they took a recognition memory test involving old and new nonfamous names. In this way, declarative (explicit) memory and nondeclarative (implicit) memory were placed in opposition. That is, recollection that a name had been recently presented (and was therefore nonfamous) opposed the focilitatory effect by which prior presentation ordinarily increases the tendency to judge that name as famous. Normal subjects exhibited good recognition memory and no fame-judgment effect—that is, no difference in fame judgments for new and old nonfamous names. By contrast, for the amnesic patients recognition memory was poor, but astrong fame-judgment effect occurred—that is, amnesic patients judged old nonfamousnames as famous. The results provide additional evidence that the fame-judgment effect is supported fully by nondeclarative (implicit) memory and is independent of the limbic/diencephalicbrain structures damaged in amnesia.     

Childhood amnesia and distinctions between forms of memory: A comment on Wood, Brown, and Felton

Recently, Wood and his colleagues (1989) presented a case of childhood amnesia as evidence against the distinction between declarative and procedural memory that has sometimes been applied to human amnesia. Their argument was based on the observation that their patient showed some progress in school over the years, i.e., acquired some declarative knowledge, despite severely impaired day-to-day memory ability. We briefly review their case, together with a carefully studied second case of childhood amnesia not mentioned by Wood et al. Their argument is wrong in several ways. First, the utility of the declarative/procedural distinction for amnesia, or the utility of any other distinction between memory systems, depends on whether or not one kind of memory is impaired selectively, not on the severity of the impairment. In particular there is no requirement that one kind of memory be totally absent. Second, they have not provided the data necessary to support their argument; namely, data showing that the amount of declarative knowledge accumulated during years in school was better than would have been expected given the capacity for moment-to-moment or day-to-day memory. Indeed, the patient's moment-to-moment memory ability is better than represented, and the patient's progress in school was abnormally slow. Third, it is not clear that academic achievement scores provide a direct measure of declarative memory abilities (skill learning and recovery of function may also have contributed). We conclude that the evidence from childhood amnesia is fully consistent with the proposal that amnesia reflects a selective impairment in the formation of long-term declarative memory.     

Classical conditioning,awareness, and brain systems

Memory is composed of several different abilities that are supported by different brain systems. The distinction between declarative (conscious) and nondeclarative (non-conscious) memory has proved useful in understanding the nature of eyeblink classical conditioning – the best understood example of classical conditioning in vertebrates. In delay conditioning, the standard procedure, conditioning depends on the cerebellum and brainstem and is intact in amnesia. Trace conditioning, a variant of the standard procedure, depends additionally on the hippocampus and neocortex and is impaired in amnesia. Recent studies have sharpened the contrast between delay and trace conditioning by exploring the importance of awareness. We discuss these new findings in relation to the brain systems supporting eyeblink conditioning and suggest why awareness is important for trace conditioning but not for delay conditioning.     

Anterograde Episodic Memory in Korsakoff Syndrome

A profound anterograde memory deficit for information, regardless of the nature of the material, is the hallmark of Korsakoff syndrome, an amnesic condition resulting from severe thiamine (vitamin B1) deficiency. Since the late nineteenth century when the Russian physician, S. S. Korsakoff, initially described this syndrome associated with "polyneuropathy," the observed global amnesia has been a primary focus of neuroscience and neuropsychology. In this review we highlight the historical studies that examined anterograde episodic memory processes in KS, present a timeline and evidence supporting the myriad theories proffered to account for this memory dysfunction, and summarize what is known about the neuroanatomical correlates and neural systems presumed affected in KS. Rigorous study of KS amnesia and associated memory disorders of other etiologies provide evidence for distinct mnemonic component processes and neural networks imperative for normal declarative and nondeclarative memory abilities and for mnemonic processes spared in KS, from whence emerged the appreciation that memory is not a unitary function. Debate continues regarding the qualitative and quantitative differences between KS and other amnesias and what brain regions and neural pathways are necessary and sufficient to produce KS amnesia.     

The Declarative/Procedural Model of Lexicon and Grammar

Our use of language depends upon two capacities: a mental lexicon of memorized words and a mental grammar of rules that underlie the sequential and hierarchical composition of lexical forms into predictably structured larger words, phrases, and sentences. The declarative/procedural model posits that the lexicon/grammar distinction in language is tied to the distinction between two well-studied brain memory systems. On this view, the memorization and use of at least simple words (those with noncompositional, that is, arbitrary form-meaning pairings) depends upon an associative memory of distributed representations that is subserved by temporal-lobe circuits previously implicated in the learning and use of fact and event knowledge. This declarative memory system appears to be specialized for learning arbitrarily related information (i.e., for associative binding). In contrast, the acquisition and use of grammatical rules that underlie symbol manipulation is subserved by frontal/basal-ganglia circuits previously implicated in the implicit (nonconscious) learning and expression of motor and cognitive skills and habits (e.g., from simple motor acts to skilled game playing). This procedural system may be specialized for computing sequences. This novel view of lexicon and grammar offers an alternative to the two main competing theoretical frameworks. It shares the perspective of traditional dual-mechanism theories in positing that the mental lexicon and a symbol-manipulating mental grammar are subserved by distinct computational components that may be linked to distinct brain structures. However, it diverges from these theories where they assume components dedicated to each of the two language capacities (that is, domain-specific) and in their common assumption that lexical memory is a rote list of items. Conversely, while it shares with single-mechanism theories the perspective that the two capacities are subserved by domain-independent computational mechanisms, it diverges from them where they link both capacities to a single associative memory system with broad anatomic distribution. The declarative/procedural model, but neither traditional dual- nor single-mechanism models, predicts double dissociations between lexicon and grammar, with associations among associative memory properties, memorized words and facts, and temporal-lobe structures, and among symbol-manipulation properties, grammatical rule products, motor skills, and frontal/basal-ganglia structures. In order to contrast lexicon and grammar while holding other factors constant, we have focused our investigations of the declarative/procedural model on morphologically complex word forms. Morphological transformations that are (largely) unproductive (e.g., in go—went, solemn—solemnity) are hypothesized to depend upon declarative memory. These have been contrasted with morphological transformations that are fully productive (e.g., in walk—walked, happy—happiness), whose computation is posited to be solely dependent upon grammatical rules subserved by the procedural system. Here evidence is presented from studies that use a range of psycholinguistic and neurolinguistic approaches with children and adults. It is argued that converging evidence from these studies supports the declarative/procedural model of lexicon and grammar.     

Influence of prior events on cognitive judgments in amnesia.

Amnesic patients and control Ss read the names of famous and nonfamous persons. Subsequently, both groups were more likely to designate a name as famous if it had been encountered previously. The facilitatory effect of prior presentation was similar for amnesic patients and control Ss and similar for famous and nonfamous names. For amnesic patients, the effect occurred despite severely impaired recognition memory for the names. In a 2nd experiment, recombining the first and last names that had been presented together did not diminish the facilitatory effect of prior presentation, which indicates that the effect does not depend on forming an association between first and last names. The results show that nondeclarative (implicit) memory can support the acquisition of information that is specific (e.g., names of persons) and that has no preexisting representation (e.g., nonfamous names).     

A longitudinal study of the performance of the elderly and young on the Tower of Hanoi puzzle and Rey recall

Normal performance on the Tower of Hanoi puzzle by amnesic patients has been taken as support for viewing this problem solving task as having a nondeclarative memory component. Individuals in each decade of life between the 20s and 80s were asked to solve this puzzle four times in four sessions with intersession intervals from 1 to 7 days (Davis & Keller, 1998). Participants in their 70s and 80s were significantly impaired compared to participants in their 20s and 30s. The elderly were also significantly impaired on five immediate trials of a 15 words verbal recall test. Participants were readministered these tests an average of 6.6 years later for the elderly (n = 12) and 7.7 years later for the young (n = 11). For the Tower of Hanoi, the performance of the elderly, but not the young individuals, was significantly poorer than their original performance. For the verbal recall test, no significant change over time was detected for the young or elderly participants. These findings support the view that some nondeclarative and/or problem solving tasks demonstrate as great or greater decline with age than some declarative tasks.     

What differentiates declarative and procedural memories: reply to Cohen, Poldrack, and Eichenbaum (1997)

CPE claim that procedural and declarative representations differ on two important dimensions: flexibility and compositionality. I have proposed that the apparent flexibility of a memory depends entirely on the transfer conditions. Any retest is, in some sense, a test of flexibility, because something has changed since the original encoding episodic. I have argued that if one changes something that does not provide support to memory performance, the memory will appear flexible, and resistant to changes in the environment. If one changes the very thing that the representation codes, the memory will appear inflexible and easily disrupted by changes in the environment. This principle is equally true for procedural and declarative memory. CPE contend that procedural representations lack compositionality. An ideal test of this claim would examine the representation of a task that is widely agreed to be procedural (e.g. that has been demonstrated to be learned normally by amnesic patients, and in the absence of awareness by neurologically intact subjects). Such experiments appear not to have been conducted, and the fact is that many tasks that are widely agreed to be procedural probably are not compositional. They appear to be, as CPE contend, biases in a processing system; it is hard to imagine how repetition priming could be compositional. Nevertheless, this is not true of all procedural memories. There is a good deal of evidence that motor behaviour is organised hierarchically and has compositionality. There is every reason to think that most if not all motor behaviour is procedural; motor behaviour might be driven by goals that are declarative, but the low-level operations that actually manipulate effectors are closed to consciousness, do not depend on the medial temporal lobe or diencephalon, and would therefore be classified as procedural. CPE framed their theory of differences between procedural and declarative memory systems as an account of the deficit in amnesic patients. They therefore predict that the learning of amnesic patients should not show flexibility or compositionality. There is already at least one study showing learning in amnesic patients that is as flexible as that of control participants (Knowlton & Squire, 1996). There are not, to my knowledge, data on whether the motor skill learning of amnesic patients shows compositionality, but one might expect that it would, given that it does in neurologically intact participants, and given that motor skill learning appears unimpaired in amnesic patients. Thus, the conception of declarative and procedural memory provided by CPE may not provide a complete account of amnesic performance. The anatomic distinction between procedural and declarative memory systems appears quite strong, and there is therefore reason to believe that there are accompanying computational differences. There does not, however, appear to be sufficient evidence to support those differences proposed by CPE.     

Declarative strategies persist under increased cognitive load

When humans simultaneously execute multiple tasks, performance on individual tasks suffers. Complementing existing theories, this article poses a novel question to investigate interactions between memory systems supporting multi-tasking performance: When a primary and dual task both recruit declarative learning and memory systems, does simultaneous performance of both tasks impair primary task performance because learning in the declarative system is reduced, or because control of the primary task is passed to slower procedural systems? To address this question, participants were trained on either a perceptual categorization task believed to rely on procedural learning or one of three different categorization tasks believed to rely on declarative learning. Task performance was examined with and without a simultaneous dual task thought to recruit working memory and executive attention. To test whether the categories were learned procedurally or declaratively, the response keys were switched after a learning criterion had been reached. Large impairments in performance after switching the response keys are taken to indicate procedural learning, and small impairments are taken to indicate declarative learning. Our results suggest that the declarative memory categorization tasks (regardless of task difficulty) were learned by declarative systems, regardless of whether they were learned under dual-task conditions.     

Extensions of the survival advantage in memory: examining the role of ancestral context and implied social isolation

Recent work (e.g., Nairne & Pandeirada, 2010) has shown that words are remembered better when they have been processed for their survival value in a grasslands context than when processed in other contexts. It has been suggested that this is because human memory systems were shaped by evolution specifically to help humans survive. Thus far, the survival processing advantage has mainly been shown with grasslands contexts, which are thought to be particularly relevant to human evolution. The present study demonstrated the survival processing advantage with other contexts (e.g., lost in a jungle), including with contexts that should not, in and of themselves, be relevant to human evolution (e.g., lost in outer space). We further examined whether implied social isolation plays a critical role in the survival advantage to memory by comparing scenarios in which the person is alone versus with other people present (e.g., lost at sea alone or with others), and whether the perceived source of danger is social isolation or other human attackers. A survival advantage was shown in both the isolation and the group settings, and whether the primary source of danger was isolation or other human attackers did not matter. These findings suggest that the survival advantage in memory is not dependent on evolutionarily relevant physical contexts (e.g., grasslands) or particular sources of perceived danger (social isolation vs. perceived attackers), showing the advantage to be robust and applicable to a variety of scenarios.     

Memory in autistic spectrum disorder

Behavioral evidence concerning memory in forms of high-functioning autism (HFA) and in moderately low-functioning autism (M-LFA) is reviewed and compared. Findings on M-LFA are sparse. However, it is provisionally concluded that memory profiles in HFA and M-LFA (relative to ability-matched controls) are similar but that declarative memory impairments are more extensive in M-LFA than in HFA. Specifically, both groups have diminished memory for emotion- or person-related stimuli. Regarding memory for nonsocial stimuli, both groups probably have mental-age-appropriate nondeclarative memory, and within declarative memory, both groups have mental-age-appropriate immediate free recall of within-span or supraspan lists of unrelated items, as well as cued recall and paired associate learning. By contrast, recognition is largely unimpaired in HFA but moderately impaired in M-LFA, and free recall of meaningful or structured stimuli is moderately impaired in HFA but more severely impaired in M-LFA. Theoretical explanations of data on declarative memory in HFA identify problems in the integrative processing, or the consolidation and storage, of complex stimuli or a specific problem of recollection. Proposed neural substrates include the following: disconnectivity of primary sensory and association areas; dysfunctions of medial prefrontal cortex, hippocampus, or posterior parietal lobe; or combinations of these associated with neural disconnectivity. Hypothetically, perirhinal dysfunction might explain the more extensive declarative memory impairments in M-LFA. Foreseeable consequences of uneven memory abilities in HFA and M-LFA are outlined, including possible effects on language and learning in M-LFA. Finally, priorities for future research are identified, highlighting the urgent need for research on memory in lower functioning individuals.