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The effect of scopolamine on memory and attention: a systematic review and meta-analysis.

BACKGROUND: Scopolamine is a muscarinic receptor antagonist and is widely utilized as a "memory-loss model." However, its impact across different memory and attention tasks and using different modes of administration has yet to be clearly evaluated. This systematic review and meta-analysis investigates the effect of scopolamine, across all routes of administration and across different dosages, on memory and attention performance in healthy humans (PROSPERO ID: CRD42024531634). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched (on 20 April 2024) for studies that utilized scopolamine and assessed memory and/or attention. Random-effects meta-analyses were conducted across a range of memory and attention tasks using "Comprehensive Meta-Analysis," Version 3, to evaluate differential pharmacological effects on cognitive tasks between the scopolamine and placebo groups. RESULTS: Forty-six studies fulfilled the inclusion and exclusion criteria. Scopolamine negatively impaired performance on all memory tasks (immediate memory, delayed recall, digit span, Buschke selective reminding task, and recognition memory) and led to slower reaction times for three of the five attention tasks examined (choice reaction time, simple reaction time, and rapid visual information processing) compared to placebo. Scopolamine's negative effect on memory and attention was greater with injectable (e.g., intramuscular, intravenous, and subcutaneous) compared to non-injectable routes of administration (e.g., intranasal, oral, and transdermal). CONCLUSION: This study supports the use of scopolamine as a "memory-loss model," particularly when given by an injectable route of administration. Future clinical trials should evaluate the bioavailability of scopolamine across different routes of administration to ensure therapeutic benefits outweigh any potential adverse cognitive effects.

Humans↗

Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD.

OBJECTIVE: To use fMRI to investigate whether hippocampal and entorhinal activation during learning is altered in the earliest phase of mild cognitive impairment (MCI). METHODS: Three groups of older individuals were studied: 10 cognitively intact controls, 9 individuals at the mild end of the spectrum of MCI, and 10 patients with probable Alzheimer disease (AD). Subjects performed a face-name associative encoding task during fMRI scanning, and were tested for recognition of stimuli afterward. Data were analyzed using a functional-anatomic method in which medial temporal lobe (MTL) regions of interest were identified from each individual's structural MRI, and fMRI activation was quantified within each region. RESULTS: Significantly greater hippocampal activation was present in the MCI group compared to controls; there were no differences between these two groups in hippocampal or entorhinal volumes. In contrast, the AD group showed hippocampal and entorhinal hypoactivation and atrophy in comparison to controls. The subjects with MCI performed similarly to controls on the fMRI recognition memory task; patients with AD exhibited poorer performance. Across all 29 subjects, greater mean entorhinal activation was found in the subgroup of 13 carriers of the APOE epsilon4 allele than in the 16 noncarriers. CONCLUSIONS: The authors hypothesize that there is a phase of increased medial temporal lobe activation early in the course of prodromal Alzheimer disease followed by a subsequent decrease as the disease progresses.

Aged↗

Cross-script and within-script priming in alcoholic Korsakoff patients.

In two experiments, alcoholic Korsakoff patients and control subjects studied a list of Japanese nouns written in either Hiragana or Kanji script. Word-fragment completion and recognition tests were then administered in Hiragana. When the writing script was changed between study and test phases, repetition priming in word-fragment completion was significantly attenuated but was still reliable against baseline performance. This was confirmed for both Korsakoff patients and control subjects. In contrast, the script change had little effect on recognition memory, which was severely impaired in Korsakoff patients. The results suggest that repetition priming is mediated by two different implicit processes, one that is script-specific and the other that is assumed to operate at a more abstract level.

Adult↗

The effect of early versus late onset of temporal lobe epilepsy on hemispheric memory laterality: an intracarotid amobarbital procedure study.

Thirty-three temporal lobe epilepsy (TLE) patients, 19 left TLE and 14 right TLE, underwent an intracarotid amobarbital procedure. For each patient, hemispheric memory laterality was determined by measuring the relative magnitude of recognition memory following left versus right hemisphere injection of sodium amobarbital. The patients were divided into early and late seizure onset groups, based on the median age (13 yrs) of seizure onset of the total sample. Early-onset left TLE was associated with a greater tendency toward right hemispheric representation of both verbal and visual memory compared with late-onset left TLE. Early-onset right TLE was associated with a greater tendency toward left hemispheric representation of visual, but not verbal, memory compared with late-onset right TLE. These findings indicate that interhemispheric plasticity for memory is greater in early than in late life, bidirectional, and at least partially material-specific.

Adolescent↗

Aging and individual differences in rapid two-choice decisions.

The effects of aging on performance were examined in signal detection, letter discrimination, brightness discrimination, and recognition memory, with each subject tested on all four tasks. Ratcliff's (1978) diffusion model was fit to the data for each subject for each task, and it provided a good account of accuracy and the distributions of correct and error response times. The model's analysis of the components of processing showed that aging had three main effects: The nondecision components of processing were slower and the decision criteria were more conservative for 60- to 74-year-old and 75- to 85-year-old subjects than for college students, but the quality of the evidence on which decisions were based was as good for the older subjects as for college students on some of the tasks. Individual differences among subjects in components of processing tended to be preserved across the tasks, as was shown by strong correlations across the tasks in the parameters of the model that represent the components of processing. For example, if the evidence on which a subject's decisions were based was good in one task, it tended to be good in all four tasks.

Aged↗

Relations between emotion, memory, and attention: evidence from taboo stroop, lexical decision, and immediate memory tasks.

This article reports five experiments demonstrating theoretically coherent effects of emotion on memory and attention. Experiments 1-3 demonstrated three taboo Stroop effects that occur when people name the color of taboo words. One effect is longer color-naming times for taboo than for neutral words, an effect that diminishes with word repetition. The second effect is superior recall of taboo words in surprise memory tests following color naming. The third effect is better recognition memory for colors consistently associated with taboo words rather than with neutral words. None of these effects was due to retrieval factors, attentional disengagement processes, response inhibition, or strategic attention shifts. Experiments 4 and 5 demonstrated that taboo words impair immediate recall of the preceding and succeeding words in rapidly presented lists but do not impair lexical decision times. We argue that taboo words trigger specific emotional reactions that facilitate the binding of taboo word meaning to salient contextual aspects, such as occurrence in a task and font color in taboo Stroop tasks.

Adult↗

The face typicality-recognizability relationship: encoding or retrieval locus?

Using a crossover recognition memory testing paradigm, we tested whether the effects on face recognition of the memorability component of face typicality (Vokey & Read, 1992, 1995) are due primarily to the encoding process occurring during study or to the retrieval process occurring at test. At study, faces were either veridical in form or at moderate (Experiment 1) or extreme (Experiment 2) levels of caricature. The variable of degree of facial caricature at study was crossed with the degree of caricature at test. The primary contribution of increased memorability to increased hit rate was through increased distinctiveness at study. Increased distinctiveness at test contributed to substantial reductions in the false alarm rate, too. Signal detection analyses confirmed that the mirror effects obtained were primarily stimulus/memory-based, rather than decision-based. Contrary to the conclusion of Vokey and Read (1992), we found that increments in face memorability produced increments in face recognition that were due at least as much to enhanced encoding of studied faces as they were to increased rejection of distractor faces.

Adult↗

Priming and aging: evidence of preserved memory function in an anagram solution task.

Priming effects in a test of anagram solution were compared with recognition memory in young and older adults. Age and a levels-of-processing study manipulation had little influence on priming in the anagram solution task, whereas significant effects of both of these variables were obtained in a recognition test. These findings extend those of previous studies which have shown little evidence of age differences in implicit memory tasks compared with those of explicit memory. Furthermore, they provide evidence for classifying anagram solution as an implicit memory test.

Adolescent↗

On the perceptual specificity of memory representations.

The present paradigm involved manipulating the congruency of the perceptual processing during the study and test phases of a recognition memory task. During each trial, a gaze-contingent window was used to limit the stimulus display to a region either inside or outside a 10 degrees square centred on the participant's point of gaze, constituting the Central and Peripheral viewing modes respectively. The window position changed in real time in concert with changes in gaze position. Four experiments documented better task performance when viewing modes at encoding and retrieval matched than when they mismatched (i.e., perceptual specificity effects). Viewing mode congruency effects were demonstrated with both verbal and non-verbal stimuli. The present research is motivated and discussed in terms of theoretical views proposed in the 1970s including the levels-of-processing framework and the proceduralist viewpoint. In addition, implications for current processing and multiple systems views of memory are outlined.

Humans↗

Data-driven and conceptually driven processes in partial-word identification and recognition.

Three experiments examined priming in partial-word identification (Warrington & Weiskrantz, 1968) and its relation to recognition memory. The results showed that changes in modality of presentation between study and test reduced performance on both identification and recognition. In contrast, changes in elaborative processing enhanced recognition but had no effect on identification. Furthermore, when explicit memory instructions were given, identification was changed to a cued recall test and was consequently affected by elaborative processing. We also found that the time course of forgetting in priming was different from that in recognition; priming in identification did not change over a 24-hr interval, whereas recognition declined rapidly during this interval. Overall, these results suggest that identification relies primarily on data-driven processing, whereas recognition can rely on both data-driven and conceptually driven processing.

Adult↗

Episodic memory and remembering in adults with Asperger syndrome.

A group of adults with Asperger syndrome and an IQ-matched control group were compared in remember versus know recognition memory. Word frequency was also manipulated. Both groups showed superior recognition for low-frequency compared with high-frequency words, and in both groups this word frequency effect occurred in remembering, not in knowing. Nor did overall recognition differ between the two groups. However, recognition in the Asperger group was associated with less remembering, and more knowing, than in the control group. Since remembering reflects autonoetic consciousness, which is the hallmark of an episodic memory system, these results show that episodic memory is moderately impaired in individuals with Asperger syndrome even when overall recognition performance is not.

Adult↗

Role of perirhinal cortex in object perception, memory, and associations.

The perirhinal cortex plays a key role in acquiring knowledge about objects. It contributes to at least four cognitive functions, and recent findings provide new insights into how the perirhinal cortex contributes to each: first, it contributes to recognition memory in an automatic fashion; second, it probably contributes to perception as well as memory; third, it helps identify objects by associating together the different sensory features of an object; and fourth, it associates objects with other objects and with abstractions.

Animals↗

Memory impairment in monkeys following lesions limited to the hippocampus.

This study addressed the question of how severe a memory impairment is produced by a lesion limited to the hippocampus. Monkeys with circumscribed hippocampal lesions were tested on the delayed-nonmatching-to-sample task, a test of recognition memory that is sensitive to amnesia in humans. Monkeys were given no preoperative training and were given no postoperative experience prior to training on the delayed-nonmatching-to-sample task. A marked deficit was observed. The results, taken together with those from previous studies, also provided information about the role of several factors that could potentially influence the level of memory impairment following hippocampal lesions. The level of impairment does not appear to be due to any of the following factors: time of testing after surgery, prior postoperative testing, surgical techniques, species differences, or behavioral training methods. However, preoperative training experience does appear to reduce the severity of the impairment, and this factor may account for the observation that the memory impairment associated with hippocampal lesions is sometimes very mild. Finally, a recent case of human amnesia studied in this laboratory is discussed in which a bilateral lesion limited to a portion of the hippocampus produced a well-documented memory deficit.

Animals↗

Double dissociation of memory capacities after bilateral occipital-lobe or medial temporal-lobe lesions.

Memory for recently encountered information can be reflected in conscious recall and recognition of that material, or in facilitated reprocessing of that material, an effect known as repetition priming. Repetition priming may be perceptual (form-based) or conceptual (meaning-based). A patient with bilateral occipital-lobe lesions (L.H.) and a patient with bilateral medial-temporal lobe lesions (H.M.) showed a double dissociation between visuoperceptual priming (impaired in L.H. and intact in H.M.) and visual recognition memory (intact in L.H. and impaired in H.M.). L.H. showed intact conceptual priming for visually presented words; his pattern of impaired visuoperceptual priming and intact conceptual priming is the reverse dissociation to that observed in prior studies of patients with Alzheimer's disease, in whom occipital cortices are relatively spared. These double dissociations suggest that a memory system localized to the occipital lobe mediates visuoperceptual priming effects, and that this system is independent of neural circuits mediating conceptual priming effects, and independent of the limbic-diencephalic system supporting conscious recognition of recently encountered information.

Adult↗

Effects of procedure on memory scanning of mildly mentally retarded adults.

The performance of mildly mentally retarded adults on recognition memory tasks was compared with that of nonretarded control subjects. Following Sternberg's (1969) procedure, material to be remembered was presented in a fixed-set procedure, during which subjects were tested repeatedly on the same well-learned set of material, and a varied-set procedure, during which they were only tested on a memory set once before having to learn a new set. Mean reaction times (RTs) in all groups increased linearly as the number of items in the fixed memorized set increased; but "no" RTs of retarded adults tested under the varied-set procedure did not show this pattern. There was a gradation of slopes for the linear regression functions of RT on memory set size in both procedures, from less steep for nonretarded adults to increasingly steep values for nonretarded children and retarded adults. These results suggest that retarded adults use different processing strategies in the two procedures and that rate of processing increases with increasing mental age.

Adolescent↗

Infant categorization: memory for category-level and specific item information.

In an attempt to determine whether it is necessary to postulate abstraction processes in infant categorization, three experiments assessed retention of category-level information and information specific to category members. Using a visual recognition memory procedure, 10- and 13-month-old infants were familiarized with category instances containing both shared dimensional information and idiosyncratic features. The addition of idiosyncratic features to members of the familiarization category enhanced specific item memory for 13-month-old infants. However, this was not the case for the younger infants. The results of within-category test comparisons indicated that 10-month-old infants regarded information common to all members of the category as more familiar than information specific to individual exemplars. This occurred despite evidence that specific item information was retained in memory and available for retrieval during recognition tests. The findings are discussed in relation to exemplar and abstraction models of categorization.

Attention↗

List discrimination in associative recognition and implications for representation.

Four experiments tested the predictions made by the model outlined in A. H. Criss and R. M. Shiffrin (2004b). Participants studied 2 successive lists of pairs followed by a recognition memory test for the most recent list. Some items and some pairs were repeated across the 2 lists. Critically, a given item could be repeated in the same or different type of pair. For associative recognition, performance was only affected by repetitions in the same pair type. However, in single-item recognition confusions occurred for both types of repetitions. The results are as predicted and confirm the assumption that different associative representations were stored even when the same token repeated in different pair types, whereas similar item representations were used regardless of pair type.

Association↗

Visual short-term memory, age, and imaging ability.

Visual short-term memory of young and older adults was studied in relation to imaging ability. Both recall and recognition memory tasks were used and additional variables included stimulus complexity and response delay (recognition tasks) and stimulus complexity and visual masking (recall tasks). Young and older participants were matched on visual discrimination, verbal intelligence, and imaging ability. Stimuli consisted of abstract visual patterns. Age-related decrements in recognition and recall were observed but performance was related to imaging ability only with recall tasks and only for older adults. The results were discussed with reference to mediational strategies and locus of occurrence of age-related decrements in short-term memory.

Adolescent↗