Fetal Alcohol-Exposed Rats Exhibit Differential Response to Cholinergic Drugs on a Delay-Dependent Memory Task

Fetal alcohol exposure in human and rodents produces a number of cognitive deficits including impairments in learning and memory. Recent evidence in our laboratory has shown that fetal alcohol-exposed (FAE) rats respond differently to systemic administration of cholinergic drugs when tested for vigilance and locomotor activity. The present study examined the effects of muscarinic and nicotinic agonists and antagonists on memory performance in a delayed alternation task. Subjects were male offspring of Sprague-Dawley rats fed a 35% ethanol-derived caloric diet, pair-fed with sucrose, or chow-fed with lab chow during the last 2 weeks of gestation. Rats (3 months old) were food-deprived prior to training in the T-maze. Rats were first trained in the alternation task at no delay for five sessions. Rats were then trained at longer delays (20, 60, 180 s) until all groups showed similar performance for two consecutive sessions. Each animal was then tested following systemic injections of the cholinergic antagonists scopolamine and mecamylamine (60-s delay) and the cholinergic agonists pilocarpine and nicotine (180-s delay). Rats received saline injections on alternate days of testing. The results revealed that FAE rats exhibited no impairments in alternation performance at the no delay and 20-s delay, but showed impairments on both the 60- and 180-s delays during the initial sessions. However, with additional training, FAE rats showed performance similar to that of control groups at these delays. Following both pilocarpine and nicotine injections, control groups, but not the FAE group, showed significant memory enhancement in the alternation task. Following scopolamine injections, the FAE rats showed a significant impairment, while control groups showed a nonsignificant decrease in performance. All three groups showed impairments in the alternation task following administration of mecamylamine compared to saline treatment. These findings suggest that alterations in the cholinergic system in FAE rats may underlie some of the cognitive deficits observed with prenatal alcohol exposure.     

Damage to the retrosplenial cortex produces specific impairments in spatial working memory

Mounting evidence indicates that the retrosplenial cortex (RSP) has a critical role in spatial navigation. The goal of the present study was to characterize the specific nature of spatial memory deficits that are observed following damage to RSP. Rats with RSP lesions or sham lesions were first trained in a working memory task using an 8-arm radial arm maze. Rats were allowed 5 min to visit each arm and retrieve food pellets and a 5-s delay was imposed between arm choices. Consistent with previous research, rats with RSP damage committed more errors than controls. In particular, RSP-lesioned rats committed more errors of omission (failing to visit an arm of the maze), but there were no lesion effects on errors of commission (revisiting an arm). Neither group of rats exhibited a turn bias (i.e., always turning a certain direction when choosing an arm). At the end of the training phase of the experiment, both groups had reached asymptote and committed very few errors. In the subsequent test phase, a longer delay (30-s) was imposed during some sessions. Both control and RSP-lesioned rats continued to make few errors during sessions with the standard 5-s delay, but RSP-lesioned rats were impaired at the 30-s delay and committed more errors of commission, consistent with an increase in taxing spatial working memory.     

Dietary restriction inhibits spatial learning ability and hippocampal cell proliferation in rats1

Abstract: We investigated the effect of dietary restriction on spatial learning ability and hippocampal cell proliferation in adult rats using two spatial learning tasks and immunohistochemical staining with 5‐bromo‐2′‐deoxyuridine (BrdU). Sixteen rats were divided into restricted or ad lib feeding groups at 70 days of age, and were trained in the delayed‐matching‐to‐place (DMTP) task (a working memory task) from 93 days of age, and then the Morris water maze task (a reference memory task). Dietary restriction had no effect on the DMTP task with 30 s delay and on the water maze task. However, in the DMTP task with 30 min delay, restricted rats performed significantly more poorly than ad lib rats. Quantitative analysis of hippocampal cell proliferation revealed that the density of newborn cells in restricted rats was significantly lower than that in ad lib rats. These results suggest that a loss of proliferating capacity in the hippocampus may be a candidate for an anatomical and biological basis for the cognitive decline caused by dietary restriction.     

视空工作记忆负载对真实场景搜索绩效的影响

采用视空工作记忆任务和真实场景搜索任务相结合的双任务范式, 结合眼动技术将搜索过程划分为起始阶段、扫描阶段和确认阶段, 探究视空工作记忆负载对真实场景搜索绩效的影响机制, 同时考查试次间搜索目标是否变化、目标模板的具体化程度以及搜索场景画面的视觉混乱度所起的调节作用。结果表明, 视空工作记忆负载会降低真实场景搜索的成绩, 在搜索过程中表现为视空负载条件下扫描阶段持续时间的延长、注视点数目的增加和空间负载条件下确认阶段持续时间的延长, 视空负载对搜索过程的影响与目标模板的具体化程度有关; 空间负载会降低真实场景搜索的效率, 且与搜索画面的视觉混乱度有关, 而客体负载则不会。由此可见, 视空工作记忆负载对真实场景搜索绩效的影响不同, 空间负载对搜索过程的影响比客体负载更长久, 二者均受到目标模板具体化程度的调节; 仅空间负载会降低真实场景的搜索效率, 且受到搜索场景画面视觉混乱度的调节。     

The role of memory representation in the vigilance decrement

Working memory load is critically important for the overall level of performance on vigilance tasks. However, its role in a key aspect of vigilance—sensitivity decrement over time—is unclear. We used a dual-task procedure in which either a spatial or a nonspatial working memory task was performed simultaneously with a spatial vigilance task for 20 min. Sensitivity in the vigilance task declined over time when the concurrent task involved spatial working memory. In contrast, there was no sensitivity decrement with a nonspatial working memory task. The results provide the first evidence of a specific role for working memory representation in vigilance decrement. The findings are also consistent with a multiple resource theory in which separate resources for memory representation and cognitive control operations are differentially susceptible to depletion over time, depending on the demands of the task at hand.     

Strategic and automatic effects of visual working memory on attention in visual search

Previous research indicates that visual attention can be automatically captured by sensory inputs that match the contents of visual working memory. However, Woodman and Luck (2007) showed that information in working memory can be used flexibly as a template for either selection or rejection according to task demands. We report two experiments that extend their work. Participants performed a visual search task while maintaining items in visual working memory. Memory items were presented for either a short or long exposure duration immediately prior to the search task. Memory was tested by a change-detection task immediately afterwards. On a random half of trials items in memory matched either one distractor in the search task (Experiment 1) or three (Experiment 2). The main result was that matching distractors speeded or slowed target detection depending on whether memory items were presented for a long or short duration. These effects were more in evidence with three matching distractors than one. We conclude that the influence of visual working memory on visual search is indeed flexible but is not solely a function of task demands. Our results suggest that attentional capture by perceptual inputs matching information in visual working memory involves a fast automatic process that can be overridden by a slower top-down process of attentional avoidance.     

Manual performance in the cold with gloves and bare hands

Previous research aimed at quantifying and reducing the decrements encountered in performing manual tasks in cold weather has not described the relationships between task characteristics and cold-induced impairments. The amount of decrement and, often times, the optimal means for reducing the decrement, appear to be task-specific. The research reported here is one in a series of studies formulated to explore those relationships. The strategy is to use tasks from the battery developed by Fleishman (1967) to measure the factorially 'pure' abilities needed to perform all manual tasks. 24 U.S. Marines performed this battery of nine tasks across a range of cold temperatures. To determine if the decrement due to wearing gloves might be less than the decrement due to cold hands as the air temperature decreased, performance on the battery of tasks was measured with and without gloves. Only three of the tasks (abilities) were affected by cold temperatures, and the amount of decrement increased as the air temperature decreased. Three tasks deteriorated due to wearing of gloves, two of those affected by cold and one other. Temperature affected performance independently of the glove effect. Half of the subjects did not complete bare-handed testing at -18 degrees C (approximately 20 min.), indicating this is the lower end of the temperature range in which bare-handed performance for more than a few minutes is practical.     

A comparison of the effects of fimbria-fornix, hippocampal, or entorhinal cortex lesions on spatial reference and working memory in rats: short versus long postsurgical recovery period.

Using a radial maze task and different postoperative recovery periods, this experiment assessed and compared the reference and working memory performances of adult Long-Evans male rats subjected to entorhinal cortex, fimbria-fornix, and hippocampus lesions. Sham-operated rats were used as controls. In order to see whether the duration of the postsurgical recovery period would influence acquisition of the complex radial maze task, training began 1 month following surgery (Delay 1) for half the rats in each group, while for the other half training was started 6.5 months following surgery (Delay 2). The results indicated that at both recovery periods the entorhinal cortex lesions failed to affect either working or reference memory in the spatial task. Conversely, both fimbria-fornix and hippocampus lesions impaired both reference and working memory. While the reference memory deficit was generally similar in both fimbria-fornix and hippocampal lesion groups, analysis of the results for working memory indicated that at the longer delay rats with fimbria-fornix lesions were still impaired but in animals that had the hippocampus removed, working memory did not differ from that of controls. These results suggest that there was some recovery in those rats with hippocampal lesions (e.g., on the working memory task) but both hippocampal and fimbria-fornix animals were still impaired compared to controls when training was delayed 6.5 months following the operations.     

The effects of a target–stimulus reminder on performance in a novel object recognition task

The effects of original training-stimulus pre-test reminders were examined in a novel object recognition (NOR) task. NOR is a task that examines memory for complex stimuli, and is driven by the rats’ tendency to spend significantly more time exploring novel objects over those previously experienced. In this task, a delay is imposed between a training experience during which the animal is allowed to investigate a set of identical objects, and a later test exposure where the animal encounters one of the original objects and a novel object with which it has had no previous experience. Experiment 1 demonstrated that performance at 24 h is significantly worse than at an immediate delay (1 min). In the second experiment, it was demonstrated that neither a 10-s nor a 30-s reminder treatment, in the absence of training, resulted in a level of preference for novelty, a measure of memory for the original object, that was significantly greater than chance. Experiment 3 illustrated significant performance effects of a 30-s training stimulus reminder administered 15 min prior to test with a 24-h retention interval. The final experiment illustrated that the additional 30-s of object exposure is effective in enhancing performance only if it occurs shortly prior to test. Animals receiving the additional 30-s immediately following training did not experience such beneficial effects. It was concluded, based upon these results, that pre-test training-stimulus reminders in this task produce effects similar to those seen in more traditional tasks of learning and memory.     

Susceptibility of spatial and verbal working memory to demands of the central executive

We used a dual-task paradigm to examine the degree to which domain-specific spatial and verbal subsystems depend on the domain-general central executive. Forty participants were asked to retain spatial or verbal information while performing a concurrent secondary task related to simple arithmetic. The secondary tasks consisted of three cognitive processes: single-digit addition, a digit-carrying operation, and digit reading. The single-digit addition and carry operation include central executive functioning, while digit reading relies solely on the phonological loop. The single-digit addition caused a performance decrement on the spatial working memory task, while the digit reading impaired performance on the verbal working memory task. The carry operation interfered with recall accuracy on both working memory tasks. The spatial working memory task was significantly correlated with the verbal working memory task only when the secondary task was more demanding on the central executive. Our results suggest that spatial working memory rather than verbal working memory is susceptible to failure of central executive functioning and that the central executive plays an important role in regulating the cognitive demands of different domains.     

Most directed forgetting in pigeons can be attributed to the absence of reinforcement on forget trials during training or to other procedural artifacts.

In research on directed forgetting in pigeons using delayed matching procedures, remember cues, presented in the delay interval between sample and comparisons, have been followed by comparisons (i.e., a memory test), whereas forget cues have been followed by one of a number of different sample-independent events. The source of directed forgetting in delayed matching to sample in pigeons was examined in a 2 x 2 design by independently manipulating whether or not forget-cue trials in training ended with reinforcement and whether or not forget-cue trials in training included a simultaneous discrimination (involving stimuli other than those used in the matching task). Results were consistent with the hypothesis that reinforced responding following forget cues is sufficient to eliminate performance deficits on forget-cue probe trials. Only when reinforcement was omitted on forget-cue trials in training (whether a discrimination was required or not) was there a decrement in accuracy on forget-cue probe trials. When reinforcement is present, however, the pattern of responding established during and following a forget cue in training may also play a role in the directed forgetting effect. These findings support the view that much of the evidence for directed forgetting using matching procedures may result from motivational and behavioral artifacts rather than the loss of memory.     

Interactions between visual working memory and selective attention

The relationship between working memory and selective attention has traditionally been discussed as operating in one direction: Attention filters incoming information, allowing only relevant information into short-term processing stores. This study tested the prediction that the contents of visual working memory also influence the guidance of selective attention. Participants held a sample object in working memory on each trial. Two objects, one matching the sample and the other novel, were then presented simultaneously. As measured by a probe task, attention shifted to the object matching the sample. This effect generalized across object type, attentional-probe task, and working memory task. In contrast, a matched task with no memory requirement showed the opposite pattern, demonstrating that this effect is not simply due to exposure to the sample. These results confirm a specific prediction about the influence of working memory contents on the guidance of attention.     

Aging and repetition priming for targets and distracters in a working memory task

A combined working memory/repetition priming task was administered to 13 young (mean age 23) and 13 elderly (mean age 69) adults. Each participant memorized a sample target face at the beginning of a trial and then determined whether each of 13 serially presented test faces matched the sample target. In each trial, both the target and one particular distracter face were repeated during the test phase. Within-trial repetition priming effects indicated the contribution of implicit memory to task performance. Response times decreased as items were tested repeatedly within a trial, but this decrement was greater for distracters than for targets. Young and older participants were equally accurate at identifying targets, but elderly were slightly less accurate for distracters. Elderly participants showed repetition priming effects for both targets and distracters, while the young showed such effects only for distracters. The results suggest that active maintenance in working memory, but not inhibition or rejection of distracters, may suppress implicit memory systems.     

工作记忆的存储时间及目标时距对时间知觉的影响

本研究操作记忆信息与计时开始之间的时间间隔（ISI）和目标时距,探讨工作记忆影响时间判断的灵活性。被试首先记忆一个客体,然后在每个trial的最后判断测试刺激是否与记忆项相同;在延迟阶段,被试完成时间判断任务,即判断相继出现的两个刺激的时距哪个更长（或更短）。时间任务中的一个刺激与记忆内容完全相同,相应的另一个刺激与记忆内容在形状和颜色上都不同。重复条件下,被试忽略第一个刺激,仅完成时间判断任务。结果发现,时间间隔（ISI）短时,记忆匹配条件下的准确率更高,匹配刺激延长了知觉的时间;但随着时间间隔的增加,工作记忆匹配对时间判断的影响降低甚至消失。并且,长或短ISI,记忆任务或重复条件下,目标时距长时,记忆匹配反而缩短了知觉的时间。研究说明工作记忆对时间判断的影响是灵活的,受到注意或工作记忆等高级认知系统的调控。     

Delayed matching-to-sample performance: Effects of relative reinforcer frequency and of signaled versus unsignaled reinforcer magnitudes

Six pigeons were trained on a delayed red-green matching-to-sample task that arranged four delays within sessions. Matching responses intermittently produced either 1.5-s access to food or 4.5-s access to food, and nonmatching responses produced either 1.5-s or 4.5-s blackout. Two phases were conducted: a signaled phase in which the reinforcer magnitudes (small and large) were signaled by houselights (positioned either on the left or right of the chamber), and an unsignaled phase in which there was no correlation between reinforcer magnitude and houselight position. In both phases, the relative frequency with which red and green matching responses produced food was varied across five values. Both matching accuracy and the sensitivity of performance to the distribution of reinforcers for matching responses decreased with increasing delays in both phases. In addition, accuracy and reinforcer sensitivity were significantly lower on signaled small-reinforcer trials compared with accuracy and sensitivity values on signaled large-reinforcer trials and on both types of unsignaled trials. These results are discussed in the context of research on both nonhuman animal and human memory.     

Aging and Repetition Priming for Targets and Distracters in a Working Memory Task

ABSTRACT

A combined working memory/repetition priming task was administered to 13 young (mean age 23) and 13 elderly (mean age 69) adults. Each participant memorized a sample target face at the beginning of a trial and then determined whether each of 13 serially presented test faces matched the sample target. In each trial, both the target and one particular distracter face were repeated during the test phase. Within-trial repetition priming effects indicated the contribution of implicit memory to task performance. Response times decreased as items were tested repeatedly within a trial, but this decrement was greater for distracters than for targets. Young and older participants were equally accurate at identifying targets, but elderly were slightly less accurate for distracters. Elderly participants showed repetition priming effects for both targets and distracters, while the young showed such effects only for distracters. The results suggest that active maintenance in working memory, but not inhibition or rejection of distracters, may suppress implicit memory systems.     

The relationship between early life stress and working memory in adulthood: A systematic review and meta-analysis

ABSTRACT

Exposure to early life stress has been linked to impairment in cognitive functioning in adulthood. The aim of this study was to systematically review the literature on the relationship between early life stress and working memory, a central component of cognitive functioning. Database searches yielded 358 abstracts matching the search terms. Abstract screening followed by full-text review resulted in 26 publications suitable for inclusion, of which 23 were included in the meta-analysis. Results of the meta-analysis suggested exposure to early life stress was associated with poorer working memory. Even though there were a wide variety of working memory tasks used, this effect was significant for both phonological and visuospatial working memory tasks, and both visual and aural task presentation modalities. The effect was also found in samples with and without clinical psychopathology. This review provides recommendations for future research and implications for clinical practice.     

A test of the reward-value hypothesis

Rats retain source memory (memory for the origin of information) over a retention interval of at least 1 week, whereas their spatial working memory (radial maze locations) decays within approximately 1 day. We have argued that different forgetting functions dissociate memory systems. However, the two tasks, in our previous work, used different reward values. The source memory task used multiple pellets of a preferred food flavor (chocolate), whereas the spatial working memory task provided access to a single pellet of standard chow-flavored food at each location. Thus, according to the reward-value hypothesis, enhanced performance in the source memory task stems from enhanced encoding/memory of a preferred reward. We tested the reward-value hypothesis by using a standard 8-arm radial maze task to compare spatial working memory accuracy of rats rewarded with either multiple chocolate or chow pellets at each location using a between-subjects design. The reward-value hypothesis predicts superior accuracy for high-valued rewards. We documented equivalent spatial memory accuracy for high- and low-value rewards. Importantly, a 24-h retention interval produced equivalent spatial working memory accuracy for both flavors. These data are inconsistent with the reward-value hypothesis and suggest that reward value does not explain our earlier findings that source memory survives unusually long retention intervals.     

Working memory in older subjects: Dealing with ongoing and stored information in language comprehension

The purpose of this experiment was to investigate the role of aging in working memory (WM), or at least the part involved in language comprehension, e.g., a double function of processing the ongoing information and keeping in memory the product of this processing. Young and older subjects were asked to simultaneously detect incongruities in sentences and keep increasing longer series of words (3, 4, or 5) in memory. The difficulty of incongruity detection was manipulated by variation of the number of intervening words (0, 6, or 12) between two critical words. Incongruity detection was assumed to be linked to the processing of information function of working memory. The concurrent mnemonic load consisted of material previously processed, and was assumed to be linked to the storage function of WM. Results showed that an increment in incongruity-detection difficulty led to a greater decrement in accuracy in older than in young subjects, indicating an impairment in the information-processing function. On the other hand, an increment in concurrent mnemonic load led to a slightly smaller decrement in accuracy in older subjects. Furthermore, fewer words from this mnemonic load were recalled in older subjects. It is suggested that older subjects are impaired in coping with both requirements of the task, and tend to sacrifice the storage of information recently processed to devote their resources to the immediate processing component of the task. These results are discussed in relation to their implications for language comprehension.     

Monkey memory: same/different concept learning, serial probe acquisition, and probe delay effects

Three rhesus monkeys were trained and tested in a same/different task with six successive sets of 70 item pairs to an 88% accuracy on each set. Their poor initial transfer performance (55% correct) with novel stimuli improved dramatically to 85% correct following daily item changes in the training stimuli. They acquired a serial-probe-recognition (SPR) task with variable (1-6) item list lengths. This SPR acquisition, although gradual, was more rapid for the monkeys than for pigeons similarly trained. Testing with a fixed list length of four items at different delays between the last list item and the probe test item revealed changes in the serial-position function: a recency effect (last items remembered well) for 0-s delay, recency and primacy effects (first and last list items remembered well) for 1-, 2-, and 10-s delays, and only a primacy effect for the longest 30-s delay. These results are compared with similar ones from pigeons and are discussed in relation to theories of memory processing.