Apo E influences declarative and procedural learning in age-associated memory impairment.

Age-associated memory impairment (AAMI) is a clinical entity which was originally described to define memory problems linked to normal aging. Apolipoprotein E and ACE genes have both been associated with cognitive impairment in aging and dementia. The purpose of this study was to investigate memory and executive functions in AAMI according to the genetic background. We found that subjects carrying the Apo E epsilon4 allele exhibit lower memory performance on tests of both declarative and procedural memory. We did not find differences on frontal lobe tests. These findings give further support to the hypothesis concerning a genetic susceptibility for cognitive impairment in aging.     

Aspects of grammar sensitive to procedural memory deficits in children with specific language impairment

Procedural deficit hypothesis claims that language deficit in children with specific language impairment is affiliated to sequence learning problems. However, studies did not explore on aspects of grammar vulnerable to sequence learning deficits. The present study makes predictions for aspects of grammar that could be sensitive to procedural deficits based on core ideas of procedural deficit hypothesis. The hypothesis for the present study was that the grammatical operations that require greater sequencing abilities (such as inflectional operations) would be more affected in children with language impairment. Further, the influence of sequencing difficulties would be even greater in agglutinating inflectional languages. An adapted serial reaction time task for sequence learning measurements along with grammatical tasks on derivation, inflection, and sentence complexity were examined on typically developing and language impaired children. Results were in favor of procedural deficit hypothesis and its close relation to non-adjacent grammatical operations. The findings were discussed using procedural deficits, declarative compensatory mechanism, and statistical learning deficits.     

Specific language impairment is not specific to language: the procedural deficit hypothesis

Specific Language Impairment (SLI) has been explained by two broad classes of hypotheses, which posit either a deficit specific to grammar, or a non-linguistic processing impairment. Here we advance an alternative perspective. According to the Procedural Deficit Hypothesis (PDH), SLI can be largely explained by the abnormal development of brain structures that constitute the procedural memory system. This system, which is composed of a network of inter-connected structures rooted in frontal/basal-ganglia circuits, subserves the learning and execution of motor and cognitive skills. Crucially, recent evidence also implicates this system in important aspects of grammar. The PDH posits that a significant proportion of individuals with SLI suffer from abnormalities of this brain network, leading to impairments of the linguistic and non-linguistic functions that depend on it. In contrast, functions such as lexical and declarative memory, which depend on other brain structures, are expected to remain largely spared. Evidence from an in-depth retrospective examination of the literature is presented. It is argued that the data support the predictions of the PDH, and particularly implicate Broca's area within frontal cortex, and the caudate nucleus within the basal ganglia. Finally, broader implications are discussed, and predictions for future research are presented. It is argued that the PDH forms the basis of a novel and potentially productive perspective on SLI.     

Dopamine-antagonistic, anticholinergic, and GABAergic effects on declarative and procedural memory functions

Declarative and procedural memory functions are related to dissociable neuroanatomic substrates. In the present study differential effects of pharmacologically induced changes in dopaminergic, GABAergic, and cholinergic activity in the brain on declarative (object and face recognition, immediate and delayed word recall) and procedural memory processes (compensatory tracking) were investigated. In a double-blind design, either 3 mg of haloperidol, 11 mg of midazolam, 1 mg of scopolamine, or placebo were administered to 80 healthy volunteers randomly assigned to one of the four drug conditions. Although all three drugs produced a detrimental effect on immediate and delayed word recall, recall performance was substantially more impaired by the benzodiazepine midazolam than by either haloperidol or scopolamine. While recognition of faces was affected by neither of the drugs, performance on object recognition was significantly decreased by midazolam as compared to placebo. Procedural learning was markedly impaired by all drugs but, again, the observed effect was most pronounced with midazolam. Additional analyses of measures of subjective activation, cortical arousal, and psychomotor performance argued against the assumption that the observed memory-impairing effects were secondary to drug-induced sedation. The overall pattern of results revealed that memory processes are much more susceptible to changes in GABAergic than in dopaminergic or cholinergic neurotransmitter activity. Furthermore, the present findings point to the conclusion that the modulating effects of dopaminergic, GABAergic, and cholinergic neurotransmitter systems on declarative and procedural memory functions are less specific than suggested by neuropsychological studies in patients.     

Sleep states and memory processes in humans: procedural versus declarative memory systems

The present paper focuses on human studies attempting to relate sleep states to memory processes. These studies typically present learning material to participants and then examine their ability to recall this material after intervening post-training sleep or sleep deprivation. Most experiments utilize either sleep recording or sleep deprivation following task acquisition to reach their conclusions, although cueing and position emission tomography (PET) scan studies have also been done. Results strongly suggest that REM sleep is involved with the efficient memory processing of cognitive procedural material but not declarative material. Although there are some data to suggest that stage 3/4 or NREM sleep is necessary for declarative memory consolidation, NREM may in fact simply be occurring at the same time as another factor that is actually involved in the memory processing. Preliminary results suggest that the length of the NREM–REM sleep cycle may be important for declarative memory. Preliminary data also suggest that stage 2 sleep may be involved with the memory for motor procedural but not cognitive procedural tasks. Sleep researchers would do well to capitalize on the latest advancements in memory research by choosing tasks that represent special memory systems and examining their relationships to sleep states.     

Visuospatial working memory in specific language impairment: A meta-analysis

We conducted a meta-analysis of the data from studies comparing visuospatial working memory (WM) in children with specific language impairment (SLI) and typically developing (TD) children. The effect sizes of 21 studies (including 32 visuospatial storage tasks and 9 visuospatial central executive (CE) tasks) were identified via computerized database searches and the reference sections of the identified studies. Meta-analyses and moderator analyses were conducted to examine the magnitude of the differences in visuospatial storage and CE, and their relation to the inclusion criteria used for SLI and the age of the children. The results showed significant effect sizes for visuospatial storage (d = 0.49) and visuospatial CE (d = 0.63), indicating deficits in both components of visuospatial WM in children with SLI. The moderator analyses showed that greater impairment in visuospatial storage was associated with more pervasive language impairment, whereas age was not significant associated with visuospatial WM. The finding of deficits in visuospatial WM suggests domain-general impairments in children with SLI. It raises questions about the language-specificity of a diagnosis of SLI. Careful attention should thus be paid to both verbal and visuospatial WM in clinical practice, and especially in those children with pervasive language impairments.     

Relationship between dissociative symptomatology and declarative and procedural memory in adolescent psychiatric patients

The purpose of this study was to examine the relationship between dissociative symptomatology and declarative and procedural memory. Subjects were 41 consecutively admitted adolescent psychiatric patients, 13 to 19 years old. Each subject completed the Adolescent Dissociative Experiences Scale (A-DES). Declarative memory was assessed by the California Verbal Learning Test and procedural memory by the Tower of Toronto puzzle. All subjects were controlled for IQ and severity of psychiatric illness. Data analysis was done by multiple regression. Multiple regression analysis revealed a model in which 71% variance of the A-DES scores was explained by psychiatric illness and specific memory variables. This study confirms a strong interrelationship between clinical dissociation and severity of psychiatric illness. Moreover, clinical dissociation seems to be associated with specific memory dysfunctions, indicating that dissociation exerts an impact on basic information processing.     

Effects of daytime naps on procedural and declarative memory in patients with schizophrenia

Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory. Straight memory deficits and sleep disturbances are well-known in patients with schizophrenia. This study tested the hypothesis that patients with schizophrenia have a deficit in procedural and declarative memory consolidation after a short midday nap when compared to healthy controls and patients with remitted to moderate major depression.Following a normal night’s sleep, 22 healthy subjects, 20 patients with major depression and 21 patients with schizophrenia were studied in a napping and wake condition in a random-order cross-over design, early in the afternoon. To test declarative memory, the Rey-Osterrieth Complex Figure Test respectively the Taylor Complex Figure Test and, for procedural learning, a mirror tracing task were performed.The present study is the first to demonstrate significant differences between individuals with schizophrenia, depression and healthy matched controls with regard to measures of sleep and memory performance after a short period of daytime sleep (napping). In particular we found that a daytime nap of only about 40 min led to improvement of declarative memory performance in all investigated groups, whereas no beneficial effect was seen on procedural performance in the group of medicated patients with schizophrenia in contrast to healthy controls and patients with remitted to moderate major depression.     

Dissociable learning-dependent changes in REM and non-REM sleep in declarative and procedural memory systems

Sleep spindles and rapid eye movements have been found to increase following an intense period of learning on a combination of procedural memory tasks. It is not clear whether these changes are task specific, or the result of learning in general. The current study investigated changes in spindles, rapid eye movements, K-complexes and EEG spectral power following learning in good sleepers randomly assigned to one of four learning conditions: Pursuit Rotor (n=9), Mirror Tracing (n=9), Paired Associates (n=9), and non-learning controls (n=9). Following Pursuit Rotor learning, there was an increase in the duration of Stage 2 sleep, spindle density (number of spindles/min), average spindle duration, and an increase in low frequency sigma power (12-14Hz) at occipital regions during SWS and at frontal regions during Stage 2 sleep in the second half of the night. These findings are consistent with previous findings that Pursuit Rotor learning is consolidated during Stage 2 sleep, and provide additional data to suggest that spindles across all non-REM stages may be a mechanism for brain plasticity. Following Paired Associates learning, theta power increased significantly at central regions during REM sleep. This study provides the first evidence that REM sleep theta activity is involved in declarative memory consolidation. Together, these findings support the hypothesis that brain plasticity during sleep does not involve a unitary process; that is, different types of learning have unique sleep-related memory consolidation mechanisms that act in dissociable brain regions at different times throughout the night.     

Perceptual organization and visual immediate memory in children with specific language impairment.

Children with specific language impairment (LI) have deficits on some nonverbal tasks, but it is not clear if these are related to specific visuospatial deficits or to more general deficits in processing strategies. Children with LI were given two visuospatial tasks that we have shown to be sensitive to strategy use as well as specific processing deficits. In Study 1, children with LI (N=29, ages 6 to 12 years) performed significantly worse than typically developing children (N=26) on the Hierarchical Forms Memory task. In Study 2, children with LI (N=15; ages 9 to 12 years) performed significantly worse than typically developing children (N=40) on the Rey-Osterrieth Complex Figure task. Children with LI were less accurate and tended to use a fairly piecemeal (immature) strategy when copying the figure and were less likely to draw the core rectangle in a more integrated fashion during the immediate memory condition. These results suggest children with LI have subtle deficits on visuospatial tasks that may be more indicative of limitations associated with processing load and planning than of specific visuospatial processing deficits.     

Syntactic comprehension and working memory in children with specific language impairment,autism or Down syndrome

This study examined syntactic assignment for predicates and reflexives as well as working memory effects in the sentence comprehension of children with Specific Language Impairment (SLI), Down syndrome (DS), high functioning Autism (HFA) and Typical Language Development (TLD). Fifty-seven children (35 boys and 22 girls) performed a computerised picture-selection sentence comprehension task. Predicate attachment and reflexive antecedent assignment (with working memory manipulations) were investigated. The results showed that SLI, HFA and DS children exhibited poorer overall performance than TLD children. Children with SLI exhibited similar performance to the DS and HFA children only when working memory demands were higher. We conclude that children with SLI, HFA and DS differ from children with TLD in their comprehension of predicate and reflexive structures where the knowledge of syntactic assignment is required. Working memory manipulation had different effects on syntactic comprehension depending on language disorder. Intelligence was not an explanatory factor for the differences observed in performance.     

Neurobiology of specific language impairment

This review summarizes what is known about the neurobiology of specific language impairment. Despite its name, specific language impairment is frequently not specific. It is common to find associated impairments in motor skills, cognitive function, attention, and reading in children who meet criteria for specific language impairment. There is evidence that limitation in phonologic working memory may be a core deficit in specific language impairment. Both genetic and environmental factors have been shown to be important etiologic factors in specific language impairment. Structural neuroimaging studies suggest that atypical patterns of asymmetry of language cortex, white-matter abnormalities, and cortical dysplasia may be associated with specific language impairment. Abnormalities in the later stages of auditory processing have been demonstrated using auditory event-related potentials. Functional neuroimaging may cast further light on the neurobiology of specific language impairment and serve as a means of developing and evaluating therapy. A better understanding of the neurobiology of specific language impairment is critical for the rational development of therapeutic strategies to treat this common disorder.     

Sequences assessed by declarative and procedural tests of memory in amnesic patients with hippocampal damage

Previous research indicates that amnesic subjects tested on sequential learning or serial reaction time tasks can learn a repeated procedural sequence but are unable to explicitly recall the correct sequence when asked to generate the sequence. Rats with hippocampal lesions are also able to learn and remember procedural or implicit sequences but were impaired for declarative sequences. We used analogous procedures used in rats to assess the role of the hippocampus in the acquisition of declarative and procedural sequences in amnesic and control participants. Amnesic participants with damage restricted to the hippocampus and control participants were administered analogous tasks of declarative and procedural sequential learning using a computer version of the radial arm maze. The amnesic participants had slower response times during the acquisition of procedural sequences, but were not impaired compared to controls when switched to a random sequence, suggesting that both groups learned the sequence. Alternatively, the amnesic but not control participants were significantly impaired in the declarative sequence task. Our findings provide support for evolutionary continuity in cognitive function of the hippocampus in rats and humans and the dissociation between the declarative and procedural sequential learning. The performance differences on the two sequence learning tasks are likely due to the use of different strategies associated with learning sequences based on procedural versus declarative knowledge.     

Characterising compensation. (Commentary on Ullman and Pierpont, "Specific language impairment is not specific to language: the procedural deficit hypothesis")

This article considers Ullman and Pierpont's Procedural Deficit theory of Specific Language Impairment (SLI). The theory represents an innovative attempt to fill the gap between brain and cognition in SLI, and has the potential to explain the non-linguistic as well as linguistic deficits seen in this disorder. The theory is reviewed with regard to: (1) the claims it makes on the domain-specificity of language structures; (2) the falsifiability conditions of the theory; (3) the level of detail at which compensatory processes are specified; and (4) from a computational perspective, whether the inferences that the theory draws from uneven behavioural impairments to underlying structural deficits are necessary ones.     

Short-term memory and vocabulary development in children with Down syndrome and children with specific language impairment

A longitudinal comparison was made between development of verbal and visuo-spatial short-term memory and vocabulary in children with Down syndrome (DS), children with specific language impairment (SLI), and typically developing children as a control group. Participants were 12 children with DS (6 males, 6 females; mean chronological age 9y 9mo [SD 2.8 mo], range 8y 6mo to 11y 4mo); nine children with SLI (4 males, 5 females; mean chronological age 3y 9mo [SD 4.8mo], range 3y 3mo to 4y 5mo); and 12 typically developing children (5 males, 7 females; mean chronological age 4y 4mo [SD 3.9mo], range 3y 3mo to 4y 3mo). Participants were matched on mental age (mean mental age 4y 3mo). All participants completed verbal short-term memory, visuo-spatial short-term memory, and expressive and receptive vocabulary tasks on three occasions over 1 year. Similarities were seen in the clinical groups for verbal short-term memory. There was some evidence of difficulty in visuo-spatial short-term memory in the children with SLI relative to the other groups, but all three groups showed overlap in visuo-spatial short-term memory performance. At the final time-point vocabulary performance in the clinical groups was similar; the typically developing children showed higher vocabulary abilities than both clinical groups.     

Parenting Stress Index and specific language impairment

The aim of the present study was to get a differentiated view of stress experience of mothers of children with a specific language impairment with a standardised questionnaire. Our sample consisted of 63 mothers of language impaired children between 3.0 and 6.5 years consecutively recruited at the University-ENT clinic of Vienna. Parenting stress was assessed by the "Parenting Stress Index" of Abidin (1995) and the results were compared to mothers of a control group matched by sex and age of the children. The results showed significant mean differences between mothers of the clinical and the control group. In nearly all subscales mothers of language impaired children have higher stress scores than mothers of the control group. 68% of mothers of the clinical group are exposed to above-average stress levels whereas only 1.5% of mothers of children with normal language development show above-average parenting stress. For a successful intervention on children with a specific language impairment it seems to be very important to identify parental stressors and to treat and support parents too.     

Working memory representation in atypical language dominance

One of the most important factors controlling material specific processing in the human brain is language dominance, i.e. hemispheric specialization in semantic processes. Although previous studies have shown that lateralized long-term memory processes in the medial temporal lobes are modified in subjects with atypical (right) language dominance, the effect of language dominance on the neural basis of working memory (WM) has remained unknown. Here, we used functional MRI (fMRI) to study the impact of language dominance on the neural representation of WM. We conducted an n-back task in three different load conditions and with both verbal and nonverbal (spatial) material in matched groups of left and right language dominant subjects. This approach allowed us to investigate regions showing significant interactions between language dominance and material. Overall, right dominant subjects showed an increased inter-individual variability of WM-related activations. Verbal WM involved more pronounced activation of the left fusiform cortex in left dominant subjects and of the right inferior parietal lobule in the right dominant group. Spatial WM, on the other hand, induced activation of right hemispheric regions in left dominant subjects, but no specific activations in right dominant subjects. Taken together, these findings indicate that the neural basis of verbal WM processes depends on language dominance and is more mutable in right dominant subjects. The increased variability in right dominant subjects strongly suggests that a standard network of material-dependent WM processes exists in left dominant subjects, and that right dominant subjects use variable alternative networks.     

The impact of visual complexity on visual short-term memory in children with specific language impairment

Many studies have assessed visual short-term memory (VSTM) abilities in children with specific language impairment (SLI), with contrasting results: some studies observed preserved VSTM capacities, while others reported impaired VSTM. The present study explores the hypothesis that the complexity of the visual information to be encoded and stored might underlie these discrepancies. Four VSTM conditions were administered to a group of 15 children with SLI, as well as to two groups of typically developing children, matched for chronological age and for VSTM capacity for visually simple stimuli, respectively. The stimuli to be remembered varied in their visual similarity and in the number of their visual features. Across the four VSTM conditions, children with SLI showed significantly reduced performance relative to an age-matched control group, and they were more strongly affected by visual similarity and number of features when compared to a control group matched for VSTM capacity for visually simple stimuli. The present results support the hypothesis that stimulus complexity is a determining factor of the poor VSTM performances in children with SLI.     

Sources of declarative memory impairment in bipolar disorder: mnemonic processes and clinical features

BACKGROUND: There is mounting evidence that declarative memory processes are impaired in patients with bipolar disorder. However, predictors of the observed impairment are not well understood. This study seeks to: (i) better characterize the nature of declarative memory impairment in bipolar disorder, and (ii) determine the relationship between clinical variables and memory function in bipolar disorder. METHODS: 49 adult patients with bipolar disorder in varying mood states and 38 demographically matched healthy participants completed a comprehensive neurocognitive battery assessing general cognitive functioning, processing speed, and declarative memory. The California verbal learning test was used to characterize learning and memory functions. RESULTS: Although patients with bipolar disorder utilized a similar semantic clustering strategy to healthy controls, they recalled and recognized significantly fewer words than controls, suggesting impaired encoding of verbal information. In contrast, lack of rapid forgetting suggests relative absence of a storage deficit in bipolar patients. While severity of mood symptomatology and illness duration were not associated with task performance, gender and family history significantly affected memory function. CONCLUSIONS: Results suggest that declarative memory impairments in bipolar patients: (1) are consistent with deficits in learning, but do not appear to be related to different organizational strategies during learning, and (2) do not appear to be secondary to clinical state, but rather may be associated with the underlying pathophysiology of the illness.     

Working memory impairment and recovery in iron deficient children

OBJECTIVE: Iron is an important oligoelement participating in multiple metabolic processes, including the synthesis of catecholamines, and its deficiency (ID) throughout development is particularly insidious on brain maturation and the emergence of cognitive functions during school age. A working memory (WM) study in 8-10-year-old ID children is presented. It is hypothesized that an impairment in WM exists in ID school-age children and a substantial restoration of this mental ability should occur after iron supplementation. METHODS: Event-related potentials (ERPs) were recorded during the completion of a Sternberg-type task in control, ID and ID-iron supplemented children. RESULTS: ID children showed less correct answers and diminished ERP amplitude in frontal, central, parietal and temporal regions compared to control children. After iron supplementation and normalizing bodily iron stores, behavioral and ERP differences disappeared between ID and control children. CONCLUSIONS: Considering that WM is fundamentally related to attention ability, the results presented here confirm and reinforce previous observations: ID severely diminishes attention [Otero GA, Pliego-Rivero FB, Contreras G, Ricardo J, Fernandez T. Iron supplementation brings up a lacking P300 in iron deficient children. Clin Neurophysiol 2004;115:2259-66] and WM while iron supplementation substantially restores the cognitive capabilities tested. SIGNIFICANCE: This is one of very few reports using ERP showing a diminished WM capability in ID school-age children.