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Effects of cholinergic enhancement on visual stimulation, spatial attention, and spatial working memory.

We compared behavioral and neural effects of cholinergic enhancement between spatial attention, spatial working memory (WM), and visual control tasks, using fMRI and the anticholinesterase physostigmine. Physostigmine speeded responses nonselectively but increased accuracy selectively for attention. Physostigmine also decreased activations to visual stimulation across all tasks within primary visual cortex, increased extrastriate occipital cortex activation selectively during maintained attention and WM encoding, and decreased parietal activation selectively during maintained attention. Finally, lateralization of occipital activation as a function of the visual hemifield toward which attention or memory was directed was decreased under physostigmine. In the case of attention, this effect correlated strongly with a decrease in a behavioral measure of selective spatial processing. Our results suggest that, while cholinergic enhancement facilitates visual attention by increasing activity in extrastriate cortex generally, it accomplishes this in a manner that reduces expectation-driven selective biasing of extrastriate cortex.

Acetylcholine↗

Influence of a visuo-spatial, verbal and central executive working memory task on postural control.

In this study, participants were required to perform different working memory (WM) tasks (a verbal task, a visuo-spatial task with two levels of difficulty and a central executive task) under different challenges to postural control (sitting, shoulder width stance and tandem stance). When a WM task was added, changes in postural sway were characterized by an increase in frequency and decrease in amplitude of sway indicating a tighter control. We found no changes in postural control between the different types of WM tasks, which might support a general capacity limitation hypothesis. However, no changes were found in performance of the WM when postural stance was modified and no changes were found in postural sway, when the difficulty level of the visuo-spatial task was modified. Consequently, the results seem to indicate that the addition of a WM task, regardless of task type or task difficulty, forces the central nervous system to choose a tighter control strategy.

Adult↗

Verbal working memory storage and processing deficits in HIV-1 asymptomatic and symptomatic individuals.

BACKGROUND: Verbal working memory (WM), which relies on intact functioning of frontostriatal circuits, has been suggested as a cognitive domain that is preferentially affected in HIV-1 infection. Although several studies have found WM impairments in HIV-1 infected patients, Baddeley's classic WM model has not been studied extensively in this population. METHODS: We used two cognitive neuropsychological approaches to examine verbal WM deficits in 18 HIV-1 seronegative, 16 HIV-1 asymptomatic, and 20 HIV-1 symptomatic patients. First, based on Baddeley's WM model of the Phonological Loop, we used the phonological similarity effect and the irrelevant speech effect to evaluate each individual's phonological store, and the word-length effect and the articulatory suppression effect to evaluate the articulatory control process. Secondly, an individual differences approach, which focuses on the capacity limitation of the WM system and potentially integrates the functions of Baddeley's Central Executive component with the Phonological Loop, was adopted. We evaluated each patient's simultaneous storage and processing of auditory material using the Verbal Memory Span test. RESULTS: The HIV-1 symptomatic individuals, but not the HIV-1 asymptomatic subjects, demonstrated impaired short-term storage of verbal material in the phonological store on Baddeley's measures. Although the HIV-1 asymptomatic and symptomatic subjects demonstrated intact rehearsal of speech-based material in the articulatory control process, both groups demonstrated impairment on the Verbal Memory Span test. CONCLUSIONS: These findings suggest that deficits in simultaneous short-term storage and processing occur during both early and later stages of HIV-1 infection.

Adult↗

Determining inhibition: Individual differences in the 'lexicon context' trade-off during lexical ambiguity resolution in working memory.

The current experiment assessed the relation between inhibitory mechanisms underlying language processing in working memory (WM) and the influence of a postulated internal cognitive trade-off between lexicon and context factors driving inhibition in sentence processing. Participants with high and low WM span (Daneman & Carpenter, 1980) were presented with sentences that began with an ambiguous noun (being both homographic and homophonic). A cue towards the relevant meaning of the ambiguous word was presented three words later by another noun. Immediately after the cue, a verb was presented that finally disambiguated the ambiguous noun. In half of the cases, the final disambiguation was congruent with the disambiguation cue. In the other half, subjects had to realize that it was not the cued but the other meaning, which turned out to be relevant in the actual sentence. This experimental paradigm was identical to the one used in Gunter et al. (2003). In contrast to the original experiment, the filler items in the present study were unambiguous. Both groups showed a smaller N400 component for the cue related to the dominant as compared to the subordinate meaning, suggesting that the dominant meaning was more active in WM than the subordinate one. In the original experiment, only the high-span subjects manifested this effect. Thus, a change in the global experimental setting changed the use of WM-related inhibitory processes. Data also suggest that, as a default strategy, the lexicon-context trade-off of high-span subjects relies more on lexicon information than does that of low-span subjects.

Adult↗

Working memory span and the role of proactive interference.

The authors investigated the possibility that working memory span tasks are influenced by interference and that interference contributes to the correlation between span and other measures. Younger and older adults received the span task either in the standard format or one designed to reduce the impact of interference with no impact on capacity demands. Participants then read and recalled a short prose passage. Reducing the amount of interference in the span task raised span scores, replicating previous results (C. P. May, L. Hasher, & M. J. Kane, 1999). The same interference-reducing manipulations that raised span substantially altered the relation between span and prose recall. These results suggest that span is influenced by interference, that age differences in span may be due to differences in the ability to overcome interference rather than to differences in capacity, and that interference plays an important role in the relation between span and other tasks.

Adolescent↗

Identification of tone duration, line length, and letter position: an experimental approach to timing and working memory deficits in schizophrenia.

Patients with schizophrenia display numerous cognitive deficits, including problems in working memory, time estimation, and absolute identification of stimuli. Research in these fields has traditionally been conducted independently. We examined these cognitive processes using tasks that are structurally similar and that yield rich error data. Relative to healthy control participants (n = 20), patients with schizophrenia (n = 20) were impaired on a duration identification task and a probed-recall memory task but not on a line-length identification task. These findings do not support the notion of a global impairment in absolute identification in schizophrenia. However, the authors suggest that some aspect of temporal information processing is indeed disturbed in schizophrenia.

Adult↗

The generality of working memory capacity: a latent-variable approach to verbal and visuospatial memory span and reasoning.

A latent-variable study examined whether verbal and visuospatial working memory (WM) capacity measures reflect a primarily domain-general construct by testing 236 participants in 3 span tests each of verbal WM. visuospatial WM, verbal short-term memory (STM), and visuospatial STM. as well as in tests of verbal and spatial reasoning and general fluid intelligence (Gf). Confirmatory' factor analyses and structural equation models indicated that the WM tasks largely reflected a domain-general factor, whereas STM tasks, based on the same stimuli as the WM tasks, were much more domain specific. The WM construct was a strong predictor of Gf and a weaker predictor of domain-specific reasoning, and the reverse was true for the STM construct. The findings support a domain-general view of WM capacity, in which executive-attention processes drive the broad predictive utility of WM span measures, and domain-specific storage and rehearsal processes relate more strongly to domain-specific aspects of complex cognition.

Adolescent↗

Effect of focus on verbal working memory: critical role of the focus word in reading.

The effect of focus on working memory was investigated with the reading span test (RST). In two experiments, the span scores and the number of intrusion errors were compared between the focused RST the and the nonfocused RST. Focus word was defined as the most important word for comprehending a sentence. For the focused RST, the target word to be maintained was the focus word for the sentence. In the nonfocused RST, however, the target word was not the focus word for the sentence. The results of both experiments showed that RST span scores were higher for the focused RST than for the nonfocused RST, and intrusion errors were found to increase for the nonfocused RST. In Experiment 2, the effect of focus was compared between high-span and low-span subjects. An effect of sentence length was also investigated. The result showed that low-span subjects were more affected than were high-span subjects by whether the word to be remembered was the focus word. The effect of sentence length was not confirmed. These findings suggest that the low-span subjects had deficits in their ability to establish and/or inhibit mental focus when faced with conflict situations in reading.

Humans↗

Individual differences in working memory capacity and learning: evidence from the serial reaction time task.

High and low working memory (WM) capacity individuals performed the serial reaction time task under both incidental and intentional learning conditions to determine the role of WM capacity in the learning of sequential information. WM capacity differences emerged in conditions of intentional but not incidental learning, indicating that individual differences in WM capacity occur in tasks requiring some form of control, with little difference appearing on tasks that required relatively automatic processing. Furthermore, an index of learning was significantly related to a measure of general fluid intelligence under intentional conditions only. Thus, the degree of learning was significantly related to higher order cognition, but only when intentional processing was emphasized.

Awareness↗

Wistar-Kyoto rats in the Morris water maze: impaired working memory and hyper-reactivity to stress.

Wistar-Kyoto (WKY) rats were tested as a potential animal model for memory dysfunction. These animals were reported to be highly reactive to stress and this was associated with findings of alterations in their hippocampal cholinergic activity. Since hippocampal cholinergic hypofunction is often associated with deficits in memory processes, untreated WKY rats were tested here in a working memory task in the Morris water maze. Animals were tested for five daily sessions, with two identical trials per day, and their performance was compared to that of Sprague-Dawley (SD) rats. Results show that WKY rats failed to improve their performance both from day to day and within the two trials each day. This suggests impaired memory capabilities of WKY rats and may support their use as an animal model of memory dysfunction. However, because of their increased tendency to float, speed of performance was also reduced in WKY compared to SD rats. This difference may be associated with their increased reactivity to stress. The combination of memory dysfunction and stress hyper-reactivity seen in WKY rats may be used to study the association between these two functions, particularly the possible interaction between memory and depression.

Animals↗

Working memory maintenance contributes to long-term memory formation: neural and behavioral evidence.

Theories of human memory have led to conflicting views regarding the relationship between working memory (WM) maintenance and episodic long-term memory (LTM) formation. Here, we tested the prediction that WM maintenance operates in two stages, and that processing during the initial stage of WM maintenance promotes successful LTM formation. Results from a functional magnetic resonance imaging study showed that activity in the dorsolateral prefrontal cortex and hippocampus during the initial stage of WM maintenance was predictive of subsequent LTM performance. In a behavioral experiment, we demonstrated that interfering with processing during the initial stage of WM maintenance impaired LTM formation. These results demonstrate that processing during the initial stage of WM maintenance directly contributes to successful LTM formation, and that this effect is mediated by a network that includes the dorsolateral prefrontal cortex and the hippocampus.

Adult↗

Visual working memory for briefly presented scenes.

Previous studies have painted a conflicting picture on the amount of visual information humans can extract from viewing a natural scene briefly. Although some studies suggest that a single glimpse is sufficient to put about five visual objects in memory, others find that not much is retained in visual memory even after prolonged viewing. Here we tested subjects' visual working memory (VWM) for a briefly viewed scene image. A sample scene was presented for 250 ms and masked, followed 1000 ms later by a comparison display. We found that subjects remembered fewer than one sample object. Increasing the viewing duration to about 15 s significantly enhanced performance, with approximately five visual objects remembered. We suggest that adequate encoding of a scene into VWM requires a long duration, and that visual details can accumulate in memory provided that the viewing duration is sufficiently long.

Adult↗

Exposing rats to a predator impairs spatial working memory in the radial arm water maze.

This series of studies investigated the effects of predator exposure on working memory in rats trained on the radial arm water maze (RAWM). The RAWM is a modified Morris water maze that contains four or six swim paths (arms) radiating out of an open central area, with a hidden platform located at the end of one of the arms. The hidden platform was located in the same arm on each trial within a day and was in a different arm across days. Each day rats learned the location of the hidden platform during acquisition trials, and then the rats were removed from the maze for a 30-min delay period. During the delay period, the rats were placed either in their home cage (nonstress condition) or in close proximity to a cat (stress condition). At the end of the delay period, the rats were run on a retention trial, which tested their ability to remember which arm contained the platform that day. The first experiment confirmed that the RAWM is a hippocampal-dependent task. Rats with hippocampal damage were impaired at learning the location of the hidden platform in the easiest RAWM under control (non-stress) conditions. The next three experiments showed that stress had no effect on memory in the easiest RAWM, but stress did impair memory in more difficult versions of the RAWM. These findings indicate that the capacity for stress to impair memory is influenced not only by the brain memory system involved in solving the task (hippocampal versus nonhippocampal), but also by the difficulty of the task. This work should help to resolve some of the confusion in the literature regarding the heterogeneous effects of stress on hippocampal-dependent learning and memory.

Analysis of Variance↗

Working memory resource allocation by young, middle-aged, and old adults.

Three hypotheses regarding the locus of age differences in working memory were examined in an experiment in which young, middle-aged, and old adults remembered the names of persons standing in line while also performing mental addition. Instructions as to the relative importance of these two tasks were manipulated. The results are highly compatible with the hypothesis of an age-related deficit in a single pool of resources that can be allocated to different tasks. They do not support hypotheses of deficits in one or more pools used separately for processing and storage functions. Middle-aged adults performed as well as young adults and better than old adults.

Adolescent↗

Functional magnetic resonance imaging response to increased verbal working memory demands among patients with multiple sclerosis.

Multiple sclerosis (MS) patients frequently experience impaired verbal working memory (VWM). Functional magnetic resonance imaging (fMRI) may help identify neural mechanisms underlying these deficits. Neuroimaging studies of healthy adults have characterized responses associated with increased VWM demands during the n-Back task, suggesting that this experimental paradigm could help identify neural correlates of VWM deficits among MS patients. Fifteen MS patients and 15 matched control participants completed the n-Back during whole-brain fMRI. Mean signal during adjacent 0-Back blocks was subtracted, on a voxel-wise basis, from mean signal observed during n-Back blocks. Resulting difference scores for 1-, 2-, and 3-Back were compared across groups and difficulty levels. Signal intensity was positively related to difficulty level in anterior regions, including premotor, supplementary motor, and dorsolateral prefrontal cortices. MS patients exhibited significantly greater intensity in these areas compared to controls during the 1-Back, while portions of the left superior frontal gyrus, cingulate, and parahippocampal gyri were relatively less intense at more difficult levels. MS group responses were slower during the 1-Back and tended to be slower during the 3-Back; however, accuracy did not differ at any level. Lesion load was positively related to only 1-Back activity and unrelated to any performance measure. Results suggest that compensatory activity occurs among MS patients matched on performance accuracy. Furthermore, compensatory activity occurs predominantly in regions associated with VWM, and this may decline relative to controls as task demands increase. These findings may help to explain why MS patient performance decreases as a function of effort on neuropsychological tests.

Brain↗

Spatial working memory and reference memory of Brown Norway and WAG rats in a holeboard discrimination task.

To determine whether working memory (WM) and reference memory (RM) represent different aspects of spatial memory, albino WAG rats and the pigmented Brown Norway rats were tested in the acquisition, retention, and reversal of spatial orientation tasks in the holeboard, which allows the simultaneous assessment of WM and RM. Putative nonmnemonic factors, such as the speed of visiting the holes or the development of a search strategy (preferred sequence of visiting the baited set of holes) were also evaluated because they might influence WM and RM performance. The WM performance of Brown Norway rats was generally worse than that of the WAG rats. The reverse was true for the RM performance. Correlation analysis supported the notion that these two measures are independent. Differences in the speed of visiting the holes and in the development of a preferred sequence of visiting the baited set of holes could not explain the strain differences in WM and RM performance. Because spatial WM and RM appear to be independent measures in the holeboard, this task could be used to investigate whether different neural substrate(s) underlie these two memory components.

Animals↗

The neural correlates of attention orienting in visuospatial working memory for detecting feature and conjunction changes.

The neural mechanisms of attentional orienting in visuospatial working memory for change detection were investigated. A spatial cue was provided with the onset time manipulated to allow more effective top-down control with an early cue than with a late cue. The change type was also manipulated so that accurate detection depended on color or the binding of color and location. The results showed that both the frontal and parietal regions subserved the change detection task without cueing. When data were collapsed over the two change types, early cueing increased activation in the right inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) while late cueing increased activation in the right inferior parietal lobule (IPL) and temporoparietal junction (TPJ) as compared with the no-cue condition. The cue onset time led to different levels of enhancement in the frontal and posterior cortices related to top-down control and stimulus-driven orienting. For feature detection, early cueing increased activation in the right MFG and late cueing increased activation in the bilateral precuneus (PCu), right TPJ, and right cuneus. The neural correlates of conjunction detection involved the right PCu and cerebellum without cueing, were associated with the anterior MFG, left IFG, and the left STG with early cueing, and involved the right MFG, left IFG, and right IPL with late cueing. The left IFG was correlated with memory retrieval of the cued representation for conjunction detection, and the right posterior PCu was associated with maintenance and memory retrieval among competing stimuli.

Adult↗

The prefrontal cortex and working memory: physiology and brain imaging.

Sustained activity has been recorded in the prefrontal cortex during working memory tasks. First, we compare the anatomical distribution of this activity in humans and monkeys. Then, we show that it reflects many factors, maintenance of the items presented, preparation for the response, transformation of the items during the delay, task rules and task goals. Finally, we point out that sustained activity has also been recorded in other areas, such as the parietal cortex. We suggest that the key to prefrontal cortex lies not in the maintenance of sensory information but in the prospective use of that information for behaviour.

Animals↗