Stress modulates the use of spatial versus stimulus-response learning strategies in humans

Animal studies provided evidence that stress modulates multiple memory systems, favoring caudate nucleus-based "habit" memory over hippocampus-based "cognitive" memory. However, effects of stress on learning strategy and memory consolidation were not differentiated. We specifically address the effects of psychosocial stress on the applied learning strategy in humans. We designed a spatial learning task that allowed differentiating spatial from stimulus-response learning strategies during acquisition. In 13 subsequent trials, participants (88 male and female students) had to locate a "win" card out of four placed at a fixed location in a 3D model of a room. Relocating one cue in the last trial allowed inferring the applied learning strategy. Half of them participated first in the "Trier Social Stress Test." Salivary cortisol and heart rate measurements were taken. Stressed participants used a stimulus-response strategy significantly more often than controls. Subsequent verbal report revealed that spatial learners had a more complete awareness of response options than stimulus-response learners. Importantly, learning performance was not affected by stress. Taken together, stress prior to learning facilitated simple stimulus-response learning strategies in humans-at the expense of a more cognitive learning strategy. Depending on the context, we consider this as an adaptive response.     

Assessing the interplay between fear and learning in mice exposed to a live rat in a spatial memory task (MWM)

In this study we tested the hypothesis that fear might facilitate learning when experienced contextually to the task. To this purpose, learning and memory performance of CD-1 mice in a Morris Water Maze (MWM) was assessed in the presence of a live predator (rat). Results indicate that a live predator induced specific predatory-avoidance responses, such as diving behavior and thigmotaxis. The rat-exposed group showed the most adaptive strategy, balancing anti-predator behavior and escape responses, while the rat pre-exposed group showed impairment in the initial phases of the acquisition. The probe trial revealed distinct swimming patterns but equal memory abilities in the different groups. Overall, this procedure represents a novel and easy test to assess the effects of stressful stimuli, contextually to spatial learning and memory performance, in mice.     

Stress or no stress: mineralocorticoid receptors in the forebrain regulate behavioral adaptation

Corticosteroid effects on cognitive abilities during behavioral adaptation to stress are mediated by two types of receptors. While the glucocorticoid receptor (GR) is mainly involved in the consolidation of memory, the mineralocorticoid receptor (MR) mediates appraisal and initial responses to novelty. Recent findings in humans and mice suggest that under stress, the MR might be involved in the use of different learning strategies. Here, we used male mice lacking the MR in the forebrain (MR(CaMKCre)), which were subjected to 5-10 min acute restraint stress, followed 30 min later by training trials on the circular hole board. Mice had to locate an exit hole using extra- and intra-maze cues. We assessed performance and the use of spatial and stimulus-response strategies. Non-stressed MR(CaMKCre) mice showed delayed learning as compared to control littermates. Prior stress impaired performance in controls, but did not further deteriorate learning in MR(CaMKCre) mice. When stressed, 20-30% of both MR(CaMKCre) and control mice switched from a spatial to a stimulus-response strategy, which rescued performance in MR(CaMKCre) mice. Furthermore, MR(CaMKCre) mice showed increased GR mRNA expression in all CA areas of the hippocampus and an altered basal and stress-induced corticosterone secretion, which supports their role in the modulation of neuroendocrine activity. In conclusion, our data provide evidence for the critical role of MR in the fast formation of spatial memory. In the absence of forebrain MR spatial learning performance was under basal circumstances impaired, while after stress further deterioration of performance was rescued by switching behavior increasingly to a stimulus-response strategy.     

Conditional Associative Learning of Spatial and Object Information in Children with Attention Deficit/Hyperactivity Disorder

The present study assessed frontostriatal mediated memory functions in children with ADHD (N = 12) and healthy control participants (N = 12) using two tests of conditional associative learning (i.e., object and spatial) that shared similar stimulus-response association structures but that differed in terms of the demands placed upon strategic processes. Children with ADHD displayed normal performance on the object learning task but were impaired on the spatial learning task that placed greater demands on internally derived strategic processes. Secondary analyses further indicated that this strategic processing impairment cannot be attributed specifically to perseverative or working memory errors but rather appears to be related to a more general inability to maintain a high degree of consistency in responding across trials. Although the results of this study must be interpreted in light of the small sample sizes, they suggest that ADHD does not produce a basic deficit in acquiring stimulus-response associations previously shown to be associated with basal ganglia dysfunction. Rather, these findings suggest that the impaired conditional associative learning performance of children with ADHD is attributable to deficits in strategic processes previously been found to be dependent upon the integrity of the prefrontal cortex.     

Conditional associative learning of spatial and object information in children with attention deficit/hyperactivity disorder.

The present study assessed frontostriatal mediated memory functions in children with ADHD (N=12) and healthy control participants (N=12) using two tests of conditional associative learning (i.e., object and spatial) that shared similar stimulus-response association structures but that differed in terms of the demands placed upon strategic processes. Children with ADHD displayed normal performance on the object learning task but were impaired on the spatial learning task that placed greater demands on internally derived strategic processes. Secondary analyses further indicated that this strategic processing impairment cannot be attributed specifically to perseverative or working memory errors but rather appears to be related to a more general inability to maintain a high degree of consistency in responding across trials. Although the results of this study must be interpreted in light of the small sample sizes, they suggest that ADHD does not produce a basic deficit in acquiring stimulus-response associations previously shown to be associated with basal ganglia dysfunction. Rather, these findings suggest that the impaired conditional associative learning performance of children with ADHD is attributable to deficits in strategic processes previously been found to be dependent upon the integrity of the prefrontal cortex.     

Priming and stimulus-response learning in perceptual classification tasks

Participants often respond more quickly and more accurately to a repeated stimulus compared to a non-repeated one, a phenomenon known as repetition priming. In semantic classification tasks priming appears to be largely attributable to the learning of stimulus-decision and stimulus-response associations, which allow participants to bypass many of the processes engaged during initial stimulus analysis. The current study tested whether stimulus-response learning plays a similarly dominant role in priming that occurs in perceptual classification tasks. Unfamiliar objects were used as stimuli to reduce the influence of semantic processes on priming and the task switched for all test trials to eliminate stimulus-decision learning. The results showed across-task priming as measured by reaction time facilitation and improved accuracy when the response remained the same during the encoding and test phases. When the response switched, similar levels of reaction time facilitation were observed, but priming as measured by accuracy was significantly reduced and no longer significant. These findings indicate that stimulus-response learning contributes to priming in perceptual classification tasks, but does not play a dominant role. Significant stimulus-level learning that is independent of the task and response also occurs and likely indexes facilitated perceptual processing of the objects.     

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

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

Lesions of the dorsolateral or dorsomedial striatum impair performance of a previously acquired simple discrimination task

Previous evidence has suggested a specific role for the dorsal striatum, especially the dorsolateral region of the dorsal striatum, in stimulus-response learning. In a previous study, we found an impairment in animals with dorsolateral striatal lesions on a simple discrimination task (CS+/CS-), thought to require the involvement of both stimulus-reward and stimulus-response learning. It is possible that the generally poor performance of dorsolateral lesioned animals on this experiment precluded adequate exposure to stimulus-reward pairings necessary for solving this task, and, thus, had little to do with stimulus-response learning. To test this hypothesis, the performance of animals with dorsolateral and dorsomedial striatal lesions was assessed on a previously acquired simple discrimination task. To independently assess the effects of each lesion on the performance of stimulus-reward learning, dorsolateral and dorsomedial lesioned animals were assessed on a previously acquired conditioned place preference task (CPP). In agreement with our earlier experiment, and the stimulus-response interpretation of dorsolateral striatal function, animals with dorsolateral striatal lesions were found to be impaired during post-lesion performance of the simple discrimination task, but not CPP learning. Additionally, dorsomedial lesioned animals were found to be impaired in performance of the simple discrimination task, but not on the CPP task. Possible explanations for the differences between the role of the dorsomedial striatum in acquisition and expression of the simple discrimination task are proposed.     

An individual differences analysis of ability and strategy influences: age-related differences in associative learning

The relationships among abilities, strategies, and performance on an associative learning task were investigated for young (aged 17 to 34) and older adults (aged 60 to 82). Participants received extensive practice on a noun-pair task in which they could use a visual-scanning strategy or a memory-retrieval strategy. Older adults were more likely to use the scanning strategy. Age differences were reduced when comparisons were made only for participants using a retrieval strategy. Associative memory was predictive of learning on the task, and semantic memory access speed was predictive of practiced performance. Practiced performance on a memory-search task that also required associative learning was predictive of practiced noun-pair performance. Models of ability-performance relationships for skill acquisition are discussed.     

The context counts: Congruent learning and testing environments prevent memory retrieval impairment following stress

Stress before retention testing impairs memory, whereas memory performance is enhanced when the learning context is reinstated at retrieval. In the present study, we examined whether the negative impact of stress before memory retrieval can be attenuated when memory is tested in the same environmental context as that in which learning took place. Subjects learned a 2-D object location task in a room scented with vanilla. Twenty-four hours later, they were exposed to stress or a control condition before memory for the object location task was assessed in a cued-recall test, either in the learning context or in a different context (unfamiliar room without the odor). Stress impaired memory when assessed in the unfamiliar context, but not when assessed in the learning context. These results suggest that the detrimental effects of stress on memory retrieval can be abolished when a distinct learning context is reinstated at test.     

Learning strategy is influenced by trait anxiety and early rearing conditions in prepubertal male, but not prepubertal female rats

Rodents solve dual-solution tasks that require navigation to a goal by adopting either a hippocampus-dependent place strategy or a striatum-dependent stimulus-response strategy. A variety of factors, including biological sex and emotional status, influence the choice of learning strategy. In these experiments, we investigated the relationship between learning strategy and anxiety level in male and female rats prior to the onset of puberty, before the activational effects of gonadal hormones influence these processes. In the first experiment, prepubertal male rats categorized as high in trait anxiety at 26days of age exhibited a bias toward stimulus-response strategy at 28days of age, whereas age-matched females exhibited no preference in strategy regardless of anxiety level. In the second experiment, male and female rats were separated from their dams for either 15 or 180min per day during the first 2weeks of life and tested on a battery of anxiety and cognitive tasks between 25 and 29days of age. Prolonged maternal separations for 180min were associated with impaired spatial memory on a Y-maze task in both prepubertal males and females. Furthermore, prolonged maternal separations were linked to elevated anxiety and a bias for stimulus-response strategy in prepubertal males but not females. Alternatively, brief separations from dams for 15min were associated with intact spatial memory, lower levels of anxiety, and no preference for either learning strategy in both sexes. These results provide evidence of sex-specific effects of trait anxiety and early maternal separation on the choice of learning strategy used by prepubertal rodents.     

Visuospatial working memory in school-aged children exposed in utero to cocaine.

OBJECTIVE: Among the neurocognitive impairments reported as associated with prenatal cocaine exposure, slower response time, and less efficient learning in school-aged children are common to findings from several laboratories. This study presents performance data on a spatial working memory task in 75 prenatally cocaine exposed (CE) and 55 nondrug-exposed (NDE) 8- to 10-year-old children. METHODS: Children were administered a novel neuropsychological measure of immediate- and short-term memory for visuospatial information, the Groton Maze Learning Test (GMLT), a computer-based hidden maze learning test that consists of a "timed chase test" (a simple measure of visuomotor speed), eight learning trials followed by a delayed recall trial after an 8-minute delay and a reverse learning trial. Performance is expressed as correct moves per second and number of errors per trial. RESULTS: Across all trials, the cocaine-exposed group showed significantly slower correct moves per second and made significantly more errors. There were no significant main effects for amounts of alcohol, tobacco, or marijuana exposure. After an 8-minute delay and compared to the eighth trial, cocaine-exposed children showed less consolidation in learning compared to nonexposed children. When asked to complete the maze in reverse, cocaine-exposed children showed a greater decrement in performance (decreased correct moves per second and increased errors) compared to the eighth learning trial. CONCLUSIONS: Children exposed in utero to cocaine exhibit a possible impairment in procedural learning and diminished efficiency in creating and accessing an internal spatial map to master the hidden maze.     

Adult age differences in the effects of goals on self-regulated sentence processing

The authors examined age differences in adults' allocation of effort when reading text for either high levels of recall accuracy or high levels of efficiency. Participants read a series of sentences, making judgments of learning before recall. Older adults showed less sensitivity than the young to the accuracy goal in both reading time allocation and memory performance. Memory accuracy and differential allocation of effort to unlearned items were age equivalent, so age differences in goal adherence were not attributable to metacognitive factors. However, comparison with data from a control reading task without monitoring showed that learning gains among older adults across trial were reduced relative to those of the young by memory monitoring, suggesting that monitoring may be resource consuming for older learners. Age differences in the responsiveness to (information-acquisition) goals could be accounted for, in part, by independent contributions from working memory and memory self-efficacy. Our data suggest that both processing capacity ("what you have") and beliefs ("knowing you can do it") can contribute to individual differences in engaging resources ("what you do") to effectively learn novel content from text.     

Contingency proportion systematically influences contingency learning

In the color-word contingency learning paradigm, each word appears more often in one color (high contingency) than in the other colors (low contingency). Shortly after beginning the task, color identification responses become faster on the high-contingency trials than on the low-contingency trials—the contingency learning effect. Across five groups, we varied the high-contingency proportion in 10% steps, from 80% to 40%. The size of the contingency learning effect was positively related to high-contingency proportion, with the effect disappearing when high contingency was reduced to 40%. At the two highest contingency proportions, the magnitude of the effect increased over trials, the pattern suggesting that there was an increasing cost for the low-contingency trials rather than an increasing benefit for the high-contingency trials. Overall, the results fit a modified version of Schmidt’s (2013, Acta Psychologica, 142, 119–126) parallel episodic processing account in which prior trial instances are routinely retrieved from memory and influence current trial performance.     

Chronic propranolol induces deficits in retention but not acquisition performance in the water maze in mice

Agents that alter adrenergic receptors, such as "beta-blockers," also alter memory storage. However, reports suggest that beta-adrenergic receptor antagonists, such as propranolol, have conflicting behavioral effects with acute vs chronic dosing. This study was designed to evaluate the effects of chronic propranolol on retention for a spatial learning task. Adult male ICR mice were given daily injections of propranolol (2, 4, 8, or 12 mg/kg ip) or 0. 9% NaCl for 15 days prior to, and during, trials in a Morris water maze. Mice received five massed acquisition (escape) trials in each of three daily sessions, followed by a single 60-s probe trial on the fourth day. The location of the submerged platform was constant for each animal over acquisition trials, but varied across animals; starting position varied across trials. A 5 (dose) x 3 (trial blocks) mixed factorial ANOVA for escape time yielded a significant trial blocks effect only (p <.001), showing performance improving over sessions. Time spent in the target quadrant on the probe trial was shorter under all doses of propranolol when compared to vehicle group (all p <.001), indicating poorer retention of prior platform location. This effect, however, was not dose-related. Swim speed was not significantly affected by propranolol. These data demonstrate that chronic dosing with propranolol can impair retention of spatial learning, which cannot be attributed to reduced arousal or motor function.     

基于选择反应的学习迁移效应：从个人情境到社会情境

先前习得的空间不相容联结可以减少、消除甚至反转Simon效应, 这种现象被称为学习迁移效应。研究者已经在个人情境和社会情境中发现一些影响学习迁移效应的因素, 并提出短时记忆联结解释、自下而上的启动机制和反应对立策略等相关解释。未来研究需要澄清刺激-反应迁移的双向性以及学习迁移效应的认知神经机制和发展路径。     

Concurrent task effects on memory encoding and retrieval: Further support for an asymmetry

Several studies have demonstrated that divided attention at encoding significantly reduces memory performance, whereas divided attention at retrieval affects memory performance only minimally. However, the possibility exists that retrieval processes have shown such resilience because the concurrent tasks used have often not been very demanding. To assess this possibility, we used independent manipulations of the concurrent task during either encoding or retrieval that included stimulus-response compatibility and participant- versus experimenter-controlled pace. In addition, we manipulated the distribution of practice that the participants received with the primary and the concurrent tasks. The results replicated and extended those recently reported by Rohrer and Pashler (2003), indicating that although memory performance is negatively affected by divided attention at retrieval, especially with noncompatible stimulus-response mapping in the concurrent task, this effect was much smaller than that at encoding, in line with the asymmetry notion. Furthermore, experimenter versus participant control of the concurrent task had no effect on memory retrieval. Finally, under conditions of equal practice with both the memory and the concurrent tasks, memory retrieval was affected only to a small degree. In contrast to encoding processes, the processes involved in retrieval accuracy appear, in many cases, to be less interrupted by divided attention, although this protection requires substantial resources.     

Strategy selection in a task with spatial and nonspatial components: effects of fimbria-fornix lesions in rats.

The main purpose of the present research was to investigate the ability of rats to learn a 12-arm radial maze task that requires the concurrent utilization of both spatial and intramaze cue information. The task involves in a single trial both place and cue learning as well as reference memory (RM) and working memory (WM). Since the animal can choose place and cue arms in any order, the strategies employed to learn the task can be studied as well as the kinds of memory errors that are made. The results of Experiment 1 showed that the number of errors made on the place and cue components of the task did not differ, and that more RM than WM errors were made early during learning. As the task was learned, the animals tended to choose the place arms before choosing the intramaze cue arms, thus suggesting that a spatial strategy was employed first followed by a cue strategy. In Experiment 2 lesions of the fimbria-fornix resulted in temporary impairments in both RM and WM that were especially apparent on the spatial component of the task. The lesioned rats also switched from choosing mostly place arms early during the trial to choosing more cue arms. While fimbria-fornix lesioned rats recovered from the memory impairments with training, the change in response strategy persisted throughout postoperative testing. The procedure of combining both spatial and non-spatial components concurrently in the same task should prove of value in studying response strategies in animals.     

Leverpress escape/avoidance training increases neurotrophin levels in rat brain

In addition to their well-known role in neural development, the neurotrophins BDNF and NGF help mediate the plasticity that occurs in the brain to promote learning. Exposure to learning procedures often leads to increases in neurotrophins, while exposure to stress often results in decreases. It is unclear how the neurotrophins would respond to an aversive learning task. Therefore, BDNF and NGF content in the dorsal striatum, hippocampus, and basal forebrain was measured following discrete trial lever-press escape/avoidance conditioning. Conditioning significantly increased levels of both neurotrophins in hippocampus and basal forebrain, relative to home cage controls (HCC). Contrary to expectations, the dorsal striatum did not show any significant changes. However, significant correlations were observed between dorsal striatal neurotrophins and aspects of avoidance performance. This may indicate that the dorsal striatum is involved in the performance aspects of the task. Results are discussed in terms of the role of neurotrophins in the acquisition of new information, and the neural structures involved in different types of memory.