Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement.     

Selective attention is a primary determinant of the relationship between working memory and general learning ability in outbred mice

A single factor (i.e., general intelligence) can account for much of an individuals' performance across a wide variety of cognitive tests. However, despite this factor's robustness, the underlying process is still a matter of debate. To address this question, we developed a novel battery of learning tasks to assess the general learning abilities (GLAs) of mice. Using this battery, we previously reported a strong relationship between GLA and a task designed to tax working memory capacity (i.e., resistance to competing demands). Here we further explored this relationship by investigating which aspects of working memory (storage or processing) best predict GLAs in mice. We found that a component of working memory, selective attention, correlated with GLA comparably to working memory capacity. However, this relationship was not found for two other components of working memory, short-term memory capacity and duration. These results provide further evidence that variations in aspects of working memory and executive functions covary with general cognitive abilities.     

Exploration in outbred mice covaries with general learning abilities irrespective of stress reactivity, emotionality, and physical attributes

Across multiple learning tasks (that place different sensory, motor, and information processing demands on the animals), we have found that the performance of mice is commonly regulated by a single factor ("general learning") that accounts for 30-40% of the variance across individuals and tasks. Furthermore, individuals' general learning abilities were highly correlated with their propensity to engage in exploration in an open field, a behavior that is potentially stress-inducing. This relationship between exploration in the open field and general learning abilities suggests the possibility that variations in stress sensitivity/responsivity or related emotional responses might directly influence individuals' general learning abilities. Here, the relationship of sensory/motor skills and stress sensitivity/emotionality to animals' general learning abilities were assessed. Outbred (CD-1) mice were tested in a battery of six learning tasks as well as 21 tests of exploratory behavior, sensory/motor function and fitness, emotionality, and stress reactivity. The performances of individual mice were correlated across six learning tasks, and the performance measures of all learning tasks loaded heavily on a single factor (principal component analysis), accounting for 32% of the variability between animals and tasks. Open field exploration and seven additional exploratory behaviors (including those exhibited in an elevated plus maze) also loaded heavily on this same factor, although general activity, sensory/motor responses, physical characteristics, and direct measures of fear did not. In a separate experiment, serum corticosterone levels of mice were elevated in response to a mild environmental stressor (confinement on an elevated platform). Stress-induced corticosterone levels were correlated with behavioral fear responses, but were unsystematically related to individuals' propensity for exploration. In total, these results suggest that although general learning abilities are strongly related to individuals' propensity for exploration, this relationship is not attributable to variations in sensory/motor function or the individuals' physiological or behavioral sensitivity to conditions that promote stress or fear.     

Effects of working memory training in young and old adults

Many cognitive abilities, including working memory and reasoning ability, decline with progressing age. In this study, we investigated whether four weeks of intensive working memory training would enhance working memory and reasoning performance in an age-comparative setting. Groups of 34 young (19–36 years) and 27 older (62–77 years) adults practiced tasks representing the three functional categories in the facet model of working memory capacity: storage and processing, relational integration, and supervision. The data were compared to those of a young and an old active control group who practiced tasks with low working memory demands. A cognitive test battery measuring near and far transfer was administered before and after training. Both age groups showed increased working memory performance in the trained tasks and in one structurally similar, but nontrained, task. Young adults also improved in a task measuring word-position binding in working memory. However, we found no far transfer to reasoning in either age group. The results provide evidence that working memory performance can be improved throughout the life span. However, in contrast to a previous study in which each facet of working memory capacity was trained separately, the present study showed that training multiple functional categories simultaneously induces less transfer.     

Up-regulation of exploratory tendencies does not enhance general learning abilities in juvenile or young-adult outbred mice

"General cognitive ability" describes a trait that transcends specific learning domains and impacts a wide range of cognitive skills. Individual animals (including humans) exhibit wide variations in their expression of this trait. We have previously determined that the propensity for exploration is highly correlated with the general cognitive abilities of individual outbred mice. Here, we asked if inducing an increase in exploratory behaviors would causally promote an increase in animals' general learning abilities. In three experiments, juvenile and young-adult male CD-1 outbred mice were exposed to 12 novel environments starting at post-natal days 39 (juvenile) and 61 (young adult), after which they underwent a series of cognitive and exploratory tests as adults (beginning at post-natal day 79). Exposure to novel environments promoted increases in exploration (across multiple measures) on two different tasks, including an elevated plus maze. However, a subsequent test of general learning abilities (aggregate performance across five distinct learning tasks) determined that exposure to novel environments as juveniles or young-adults had no effect on general learning abilities in adulthood. Therefore, while exposure to novel environments promotes long-lasting increases in mice's exploratory tendencies, these increases in exploration do not appear to causally impact general learning abilities.     

Overexpression of hAPPswe impairs rewarded alternation and contextual fear conditioning in a transgenic mouse model of Alzheimer's disease

One of the hallmarks of the pathology in Alzheimer's disease is the deposition of amyloid plaques throughout the brain, especially within the hippocampus and amygdala. Transgenic mice that overexpress the Swedish mutation of human amyloid precursor protein (hAPPswe; Tg2576) show age-dependent memory deficits in hippocampus-dependent learning tasks. However, the performance of aged Tg2576 mice in amygdala-dependent learning tasks has not been thoroughly assessed. We trained young (2–4 mo) and old (16–18 mo) Tg2576 and wild-type mice in a T-maze alternation task (hippocampus-dependent) and a Pavlovian fear-conditioning task (amygdala- and hippocampus-dependent). As previously reported, old Tg2576 mice showed impaired acquisition of rewarded alternation; none of these mice reached the criterion of at least five out of six correct responses over three consecutive days. In contrast, old Tg2576 mice showed normal levels of conditional freezing to an auditory conditional stimulus (CS) and acquired a contextual discrimination normally. However, when the salience of the fear-conditioning context was decreased, old (12–14 mo) Tg2576 mice were impaired at acquiring fear to the conditioning context, but not to the tone CS. Histological examination of a subset of the mice verified the existence of amyloid plaques in the cortex, hippocampus, and amygdala of old, but not young, Tg2576 mice. Hence, learning and memory deficits in old Tg2576 mice are limited to hippocampus-dependent tasks, despite widespread amyloid deposition in cortex, hippocampus, and amygdala.     

The effect of bilingualism on lexical learning and memory across two language modalities: some evidence for a domain-specific,but not general,advantage

ABSTRACT

The present study was conducted to replicate bilingual advantages in short-term memory for language-like material and word learning in young adults and extend this research to the sign domain, ultimately with the goal of investigating the domain specificity of bilingual advantages in cognition. Data from 112 monolingual hearing non-signers and 78 bilingual hearing non-signers were analysed for this study. Participants completed a battery of tasks assessing sign and word learning, short-term memory, working memory capacity, intelligence, and a language and demographic questionnaire. Overall, the results of this study suggested a bilingual advantage in memory for speech-like material – no other advantage (or disadvantage) was found. Results are discussed within the context of recent large-scale experimental and meta-analytic studies that have failed to find bilingual advantages in domain-general abilities such as attention control and working memory capacity in young adults.     

Role of Verbal Working Memory in Complex Skill Acquisition

Although research has shown that general cognitive ability is related to performance during the initial stage of skill acquisition, empirical evidence is needed to increase understanding of the primary abilities responsible for the relation. We propose that verbal working memory is related to initial skill acquisition performance based on cognitive activities people enact when learning complex skills. After completing a general cognitive ability measure and a test of verbal working memory, 120 undergraduate students performed a complex computer simulation. The working memory test accounted for a meaningful amount of performance variance after statistically controlling for the general cognitive ability measure. These data suggest that tasks depending heavily on the activation of multiple knowledge structures may be understood in terms of individual differences in working memory.     

The Genetic and Environmental Relationship Between General and Specific Cognitive Abilities in Twins Age 80 and Older

In the first twin study of the old-old, individuals 80 years old and older, we examined the relationship between general and specific cognitive abilities from a genetic perspective. That is, we examined the extent to which genetic and environmental factors influence major group factors of cognitive abilities, independent of general cognitive ability. As part of the OctoTwin project in Sweden, general and specific cognitive abilities were assessed in 52 monozygotic and 65 same-sex dizygotic twin pairs 80 years old and older using a battery of seven tests that assess verbal, spatial, speed-of-processing, and memory performance. Results suggest that genetic effects associated with general cognitive ability ( g ) account for the correlation between g and verbal, spatial, and speed-of-processing abilities. No genetic influences were found for these specific cognitive abilities separate from g . In contrast, memory ability appears to be more distinct genetically from g than are other cognitive abilities. Comparison with younger samples suggests that cognitive abilities relating to speed of processing may be genetically dedifferentiated in the old-old.     

Working Memory and Cognitive Skills in Individuals with Down Syndrome

This work is aimed at analyzing working memory (WM) components and their relationships with other cognitive processes in individuals with Down syndrome (DS). Particular attention is given to examine whether a verbal WM deficit is due to difficulties in verbal abilities often showed by individuals with DS, or whether it is a deficit per se. A group of 20 individuals with DS was compared to a group of 20 typically developing (TD) children matched on vocabulary comprehension and to a group of 20 TD children matched on general verbal intelligence. The groups received a battery of 3 verbal and 3 visuospatial WM tasks requiring different degrees of control, and tests assessing verbal abilities (WPPSI verbal scale, PPVT), nonverbal skills (WPPSI performance scale), and logical thinking (LO). The results revealed that individuals with DS have deficits in both central executive (control) and verbal components of the WM system, and the latter one is independent of the general verbal abilities deficit. The data suggest that the development of central executive proceeds at a slower rate in individuals with DS and differently from TD children with comparable verbal abilities. The performance of individuals with DS on high-control WM tasks requires additional general resources that are strictly linked to intelligence.     

The social foundation of executive function

In this study, we propose that infant social cognition may ‘bootstrap' the successive development of domain‐general cognition in line with the cultural intelligence hypothesis. Using a longitudinal design, 6‐month‐old infants (N = 118) were assessed on two basic social cognitive tasks targeting the abilities to share attention with others and understanding other peoples' actions. At 10 months, we measured the quality of the child's social learning environment, indexed by parent's abilities to provide scaffolding behaviors during a problem‐solving task. Eight months later, the children were followed up with a cognitive test‐battery, including tasks of inhibitory control and working memory. Our results showed that better infant social action understanding interacted with better parental scaffolding skills in predicting simple inhibitory control in toddlerhood. This suggests that infants' who are better at understanding other's actions are also better equipped to make the most of existing social learning opportunities, which in turn may benefit future non‐social cognitive outcomes.     

Variations in working memory capacity predict individual differences in general learning abilities among genetically diverse mice

Up to 50% of an individuals' performance across a wide variety of distinct cognitive tests can be accounted for by a single factor (i.e., "general intelligence"). Despite its ubiquity, the processes or mechanisms regulating this factor are a matter of considerable debate. Although it has been hypothesized that working memory may impact cognitive performance across various domains, tests have been inconclusive due to the difficulty in isolating working memory from its overlapping operations, such as verbal ability. We address this problem using genetically diverse mice, which exhibit a trait analogous to general intelligence. The general cognitive abilities of CD-1 mice were found to covary with individuals' working memory capacity, but not with variations in long-term retention. These results provide evidence that independent of verbal abilities, variations in working memory are associated with general cognitive abilities, and further, suggest a conservation across species of mechanisms and/or processes that regulate cognitive abilities.     

语言能力的老化机制：语言特异性与非特异性因素的共同作用

语言能力的衰退是由于一般认知能力衰退引起的, 还是由于语言加工系统的衰退引起的, 抑或是两者的共同作用?研究中测量了青年组和老年组的一般认知能力(加工速度、工作记忆和抑制能力), 以及在词汇、句子和语篇三个水平上的语言理解能力和语言产生能力。结果发现, 一般认知能力、语言理解和语言产生能力都存在年老化现象。分层回归分析表明, 一般认知能力对语言能力的贡献, 以及语言理解能力和产生能力之间的相互贡献在青年组和老年组中是不同的, 且存在词汇、句子和语篇水平上的差异。在词汇水平上, 青年人的成绩能够被一般认知能力和另一种语言能力所显著预测, 而老年人的成绩却不受一般认知因素影响; 在句子水平上, 青年人的成绩仍能被一般认知能力或另一种语言能力所解释, 但这两类变量都无法预测老年人的任务成绩; 在语篇水平上, 青年人理解任务的成绩显著地受到产生能力影响, 而老年人的理解和产生任务成绩则分别可以被一般认知能力和语言理解能力所解释。对组间差异的回归分析表明, 一般认知能力和另一种语言能力对组间差异都有显著贡献, 且前者的贡献大于后者。上述研究结果表明, 语言能力的老化是语言特异性因素和非特异性因素共同作用的结果。     

Cognitive decline and human (Homo sapiens) aging: an investigation using a comparative neuropsychological approach

Using a comparative neuropsychological approach, the authors compared performance of younger and healthy older adults ages 65 and over on tasks originally developed to measure cognition in animals. A battery of 6 tasks was used to evaluate object discrimination, egocentric spatial abilities, visual and spatial working memory, and response shifting. Older adults performed more poorly than younger adults on tasks that evaluate egocentric spatial abilities, response shifting, and to a lesser extent object recognition. The two groups did not differ for tasks that evaluate spatial working memory and object discrimination. The impairments the authors observed in tasks that evaluate response shifting and object recognition are consistent with those found in canines and primates as well as those found in Alzheimer's disease. The results are consistent with the notion that cognitive processes supported by the amygdala and the orbitofrontal cortex are among the first to decline with increasing age in both humans and animals.     

Nature of the working memory deficit in fragile-X syndrome

Working memory performance in a group of young Fragile X males with FMR-1 full mutation was compared to a learning disabled comparison group comprising Down's syndrome males and two control groups of mainstream schoolchildren. Performance was assessed on a battery of tasks tapping the three components of working memory-phonological loop, visual-spatial sketch pad, and the central executive. The results indicated that the Fragile X group displayed a general impairment on working memory tasks that cannot be attributed to a single working memory component per se. Instead, the results suggest that Fragile X males have a working memory deficit that may be attributed to how much attentional resource a specific task requires and their overall available executive capacity, irrespective of the working memory subsystem.     

Cognitive Mediators of Age-Related Differences in Language Comprehension and Verbal Memory Performance

The present study tried to specify how much processing speed, working memory capacity, and inhibition capability contribute to the effects of aging on language performance. An individual-differences approach was used to examine the component processes that predict performance in language comprehension and verbal long-term memory tasks. A total of 151 participants aged 31-80 completed language processing tasks and a battery of tasks designed to assess processing speed, working memory, and resistance to interference. Latent-construct structural equation modeling was used to examine the relationships of these factors and age to different types of language tasks. The best fit model showed first that all the significant relationships between age and language performance are mediated through reductions in speed, resistance to interference, and working memory; this confirms the validity of the general factor approach of age-related differences in cognitive performance. The best fit model, however, also showed that the contribution of speed and resistance to interference is indirect and mediated by working memory, which appears to play a crucial role in explaining age-related differences in language performance.     

Age-related impairments of new memories reflect failures of learning,not retention

Learning impairments and the instability of memory are defining characteristics of cognitive aging. However, it is unclear if deficits in the expression of new memories reflect an accelerated decay of the target memory or a consequence of inefficient learning. Here, aged mice (19–21-mo old) exhibited acquisition deficits (relative to 3–5-mo old mice) on three learning tasks, although these deficits were overcome with additional training. When tested after a 30-d retention interval, the performance of aged animals was impaired if initial learning had been incomplete. However, if trained to equivalent levels of competence, aged animals exhibited no retention deficits relative to their young counterparts. These results suggest that age-related “memory” impairments can be overcome through a more effective learning regimen.Aging is associated with broad deficits in the acquisition of new knowledge (Matzel et al. 2008; see, for review, Gallagher and Rapp 1997; Rosenzweig and Barnes 2003), as well as impairments in the retrieval of both old and newly acquired information. While it is clear that old memories (i.e., ones obtained prior to age-related cognitive declines) do in fact become less stable with age (Gallagher 1997), it is less clear whether newly attained memories are inherently less stable in aged animals, or whether age-related memory deficits reflect a secondary consequence of inefficient learning.The majority of published data regarding cognitive aging describes impairments of animals'' learning abilities (Gage and Dunnett 1984; Markowska et al. 1994; Meliska et al. 1997; Nalbantoglu et al. 1997; Vogel et al. 2002; Matzel et al. 2008), although a smaller percentage of these studies also report animals'' performances after long retention intervals. Of those studies that report retention deficits, in most of those studies the initial learning upon which the long-term memory was based was impaired relative to young animals (e.g., Barnes and McNaughton 1985; Kinney et al. 2001a,b; Gould and Feiro 2005). Interestingly, in those few studies in which initial learning was equated across young and old animals, including studies of spatial water maze performance and appetitive instrumental responding, no retention deficits were observed, even after retention intervals as long as 21 d (Soffie and Lejeune 1991; Martinez-Serrano et al. 1996; Port et al. 1996).Although suggestive, the above experiments were not systematically designed to assess the stability of memory in aged animals as a function of the level of initial learning. In the present study, young (3–5 mo) and old (19–21 mo) male Balb/C mice were trained in three learning tasks (a spatial water maze, an egocentric Lashley III maze, and a three-choice odor discrimination). When trained to pre-asymptotic levels, aged animals exhibited both learning and retention deficits (assessed 30 d after initial training). However, when aged animals were trained to levels of competence comparable to their young counterparts, both young and old animals exhibited statistically indistinguishable levels of retention.Sixty Balb/C mice arrived in our laboratory at 2.5 mo (n = 30) or 18.5 mo (n = 30) of age. Each age category was divided into two groups of 15, one of which would receive subasymptotic training on each of the three learning tasks, and one of which would receive extended training on those tasks. Two aged mice became ill during the course of testing and were excluded from all analyses. Young mice ranged from 19.8 to 29.1 g, and aged mice from 26.2 to 37.3 g. Maintenance, food deprivation, and training conditions were as previously described (Matzel et al. 2006, 2003). Behavioral testing of young and aged mice was concluded at ∼5 and 21 mo of age, respectively.All animals were tested in three independent learning tasks. Briefly, the spatial water maze encourages mice to integrate spatial information to efficiently escape from a pool of water. In odor discrimination, animals must use a target odor (from a group of three odors) to guide their search for food. In the Lashley III maze, animals learn an egocentric sequence of turns to obtain a food reinforcer. Training on each task required 2–10 d (depending on the task and the level of training), and animals received four days of rest between tasks. A retention test was administered 30 d after the last training trial of each task.A Lashley III maze was constructed from black Plexiglas. A 3-cm-diameter white disk was located in the center of the goal box, and a 45 mg Bio-Serv food pellet (dustless rodent grain) was placed at the center of the disk and served as the reinforcer. Food-deprived animals received a day of acclimation to the maze, followed by either one or two days of training (four trials/day). On the day prior to the acclimation, animals received three Bio-Serv pellets in their home cage (thus mitigating any neophobia to the food on subsequent exposures). On the acclimation day, each mouse was confined in each of the first three alleys of the maze for 4 min, and in the final alley (containing the goal box) for 6 min. On this acclimation day, three Bio-Serv pellets were placed in the goal box. On the subsequent training day(s), each animal was placed in the start box and allowed to freely navigate the maze, during which time the number of errors to reach the goal box were recorded. (An error was constituted by a turn in the wrong direction or a retracing of a previously completed path.) Upon consuming the food pellet, the animal was returned to its home cage for a 25-min intertrial interval (ITI). All animals completed four trials during the first training day. Half of those animals then received an additional four training trials on the following day. Twenty-nine days after the last training trial, all animals received three Bio-Serv pellets in their home cages, and on the subsequent day were again tested in the maze.For the water maze, a round pool (140 cm diameter, 56 cm deep) was filled to within 20 cm of the top with water that was clouded with a water soluble black paint. A hidden 14-cm-diameter black platform was located in a fixed position 1 cm below the surface of the water. The pool was enclosed by a ceiling high black curtain on which five different light patterns (which served as spatial cues) were fixed at various positions. These light cues provided the only illumination of the maze, which was 60 Lux at the water''s surface.On the day prior to training, each animal was confined for 360 sec to the platform by a clear Plexiglas cylinder that fits around the platform. For either one or two training days (six trials Day 1, five trials Day 2), the animals were started from one of three positions, such that no consecutive trials started from the same position. After locating the platform or swimming for 90 sec, the animals were left or placed on the platform for 10 sec, after which they were placed in a holding box (for 12 min) before the start of the next trial. After the sixth or 11th training trial, animals were returned to their home cages for 3 h, and were then administered a 30-sec “probe” test in which the escape platform was removed from the maze and the time spent searching in the target quadrant was recorded. One hour later each animal received an additional training trial (intended to re-establish the search strategy employed by the animal prior to the probe test). Animals were then returned to their home cages, where a 30-d retention interval began.In odor discrimination, mice navigate through a field using unique odors to guide them. The animals learn to choose the food cup that contains the target smell when given three choices. The food cup locations are rearranged on each trial, but the accessible food is always marked by the same target odor (in this case mint). The chamber consisted of a black Plexiglas 60-cm-square field with 30-cm-high walls, which was located in a dimly lit room with high ventilation. A food cup was located in three corners. The target cup had accessible food (30 mg of chocolate puffed rice), while the remaining cups contained food that could not be accessed. A cotton tipped swab (2-cm long) was loaded with 25 μL of lemon-, mint- (the target odor), or almond-flavored extract and extended vertically from the back corner of each cup.Each animal had one day of acclimation and one day of training (consisting of four training trials). (In this task, both young and old animals reached asymptotic levels of performance [near errorless] within four training trials.) On Day 1 (adaptation), each mouse was placed in the box for 20 min with no food cups present. On the subsequent training day, a food cup was placed in three corners of the field, but only the cup associated with the mint odor contained accessible food. Each animal received four trials in which they were placed in the corner of the training chamber that did not contain a food cup. A trial continued until the animal obtained the food from the target location, at which time the animal was returned to its home cage to begin a 20 min ITI. At the end of each trial the food cups were rearranged, but mint always remained as the target odor. For each trial, the number of errors (contact with or sniffing within 2 cm of an incorrect food cup) was recorded. After the fourth training trial, the animal was returned to its home cage for a 30-d retention interval. On the 29th retention day, all animals received three pieces of chocolate flavored rice in their home cages, and on the subsequent day were again tested as in original training.     

Visuospatial working memory in Turner's syndrome

Turner's syndrome is a genetic disorder, specific to women, in which one of the X chromosomes is partially or completely deleted. This syndrome is associated with physical features such as short stature or failure in primary and secondary sexual development, together with a specific pattern of cognitive functions. It has been suggested that women affected by Turner's syndrome perform poorly in tasks measuring visuospatial abilities and have a verbal IQ significantly higher than performance IQ. Although this result has received strong empirical support, the nature of the visuospatial deficit is still unclear. Recent studies on visuospatial processes have highlighted that the underlying cognitive structure is more complex than previously suggested and several dissociations have been reported (e.g., visual vs spatial, sequential vs simultaneous, or passive vs active processes). In the present study we analyze in detail the characteristics of the visuospatial deficit associated with Turner's syndrome by presenting four young women with a comprehensive battery of tasks designed to tap all aspects of visuospatial working memory. Results confirm that Turner's syndrome is associated with a general visuospatial working memory deficit, but the pattern of performance of different cases can be different, with a greater emphasis on active visuospatial processes. and on either sequential or simultaneous spatial processes.     

Domain-specific and domain-general constraints on word and sequence learning

The relative influences of language-related and memory-related constraints on the learning of novel words and sequences were examined by comparing individual differences in performance of children with and without specific deficits in either language or working memory. Children recalled lists of words in a Hebbian learning protocol in which occasional lists repeated, yielding improved recall over the course of the task on the repeated lists. The task involved presentation of pictures of common nouns followed immediately by equivalent presentations of the spoken names. The same participants also completed a paired-associate learning task involving word–picture and nonword–picture pairs. Hebbian learning was observed for all groups. Domain-general working memory constrained immediate recall, whereas language abilities impacted recall in the auditory modality only. In addition, working memory constrained paired-associate learning generally, whereas language abilities disproportionately impacted novel word learning. Overall, all of the learning tasks were highly correlated with domain-general working memory. The learning of nonwords was additionally related to general intelligence, phonological short-term memory, language abilities, and implicit learning. The results suggest that distinct associations between language- and memory-related mechanisms support learning of familiar and unfamiliar phonological forms and sequences.