Haloperidol increases false recognition memory of thematically related pictures in healthy volunteers.

Dopamine can modulate long-term episodic memory. Its potential role on the generation of false memories, however, is less well known. In a randomized, double-blind, placebo-controlled experiment, 24 young healthy volunteers ingested a 4-mg oral dose of haloperidol, a dopamine D2 -receptor antagonist, or placebo, before taking part in a recognition memory task. Haloperidol was active during both study and test phases of the experiment. Participants in the haloperidol group produced more false recognition responses than those in the placebo group, despite similar levels of correct recognition. These findings show that dopamine blockade in healthy volunteers can specifically increase false recognition memory.

Acute cognitive effects of donepezil in young, healthy volunteers.

OBJECTIVE: The acute nootropic potential of donepezil in young healthy volunteers has not been adequately investigated mainly because in previous studies: (1) effects were assessed before peak-plasma concentration (Tmax) was reached; (2) only a few cognitive processes were assessed. Here we investigated a myriad of cognitive effects of augmentation of acetylcholine using an acute dose of donepezil in healthy adults at theoretical Tmax. METHODS: This was a double-blind, placebo controlled, parallel group design study of cognitive effects of acute oral donepezil (5 mg). Subjects were tested twice after donepezil ingestion: 90 min (time that coincides with previous testing in the literature) and 210 min. (theoretical Tmax). The test battery included tasks that tap cognitive domains that are sensitive to acetylcholine manipulations. RESULTS: At both testing times donepezil improved long-term recall of prose, objects recall, recall of spatial locations, and integration of objects with their locations, some effects having been related to self-reported mood enhancement. However, improvement of performance in the central executive measure (backward digit span) occurred only at Tmax. CONCLUSION: Positive cognitive effects of acute donepezil can be observed in various cognitive domains including mood, but its full nootropic potential is more clearly found close to theoretical peak-plasma concentration.

Effects of semantic relations, repetition of words, and list length in word list recall of Alzheimer's patients.

INTRODUCTION: Semantic relations among words and repetition enhance free recall, but it is unknown if these facilitating factors are effective in dementia. METHOD: Alzheimer's patients (MILD-Alz, MOD-Alz) were compared to healthy elderly. Fifteen-word lists were read out to the subjects. In four sets of lists the words in intermediary input positions were semantically related or not, or the midlist words were repeated, or they were repeated and semantically related. RESULTS: The usual third peak of recall of semantically related words was not observed in MOD-Alz, repetition of words did not increase recall of the patients, and the combination of relatedness and repetition benefited only MID-Alz. In a second experiment, with related or unrelated midlist words, and list length shortened from 15 to 9 words, semantic facilitation was observed in mild and moderate Alzheimer s patients, although diminished compared to controls. CONCLUSION: Progression of dementia turns facilitating factors of recall less effective.

Effects of Sulpiride on True and False Memories of Thematically Related Pictures and Associated Words in Healthy Volunteers.

Episodic memory, working memory, emotional memory, and attention are subject to dopaminergic modulation. However, the potential role of dopamine on the generation of false memories is unknown. This study defined the role of the dopamine D2 receptor on true and false recognition memories. Twenty-four young, healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a dopamine D2-receptor antagonist, just before starting the recognition memory task in a randomized, double-blind, and placebo-controlled trial. The sulpiride group presented more false recognitions during visual and verbal processing than the placebo group, although both groups had the same indices of true memory. These findings demonstrate that dopamine D2 receptors blockade in healthy volunteers can specifically increase the rate of false recognitions. The findings fit well the two-process view of causes of false memories, the activation/monitoring failures model.

Late positive slow waves as markers of chunking during encoding.

Electrophysiological markers of chunking of words during encoding have mostly been shown in studies that present pairs of related stimuli. In these cases it is difficult to disentangle cognitive processes that reflect distinctiveness (i.e., conspicuous items because they are related), perceived association between related items and unified representations of various items, or chunking. Here, we propose a paradigm that enables the determination of a separate Event-related Potential (ERP) marker of these cognitive processes using sequentially related word triads. Twenty-three young healthy individuals viewed 80 15-word lists composed of unrelated items except for the three words in the middle serial positions (triads), which could be either unrelated (control list), related perceptually, phonetically or semantically. ERP amplitudes were measured at encoding of each one of the words in the triads. We analyzed two latency intervals (350-400 and 400-800 ms) at midline locations. Behaviorally, we observed a progressive facilitation in the immediate free recall of the words in the triads depending on the relations between their items (control < perceptual < phonetic < semantic), but only semantically related items were recalled as chunks. P300-like deflections were observed for perceptually deviant stimuli. A reduction of amplitude of a component akin to the N400 was found for words that were phonetically and semantically associated with prior items and therefore were not associated to chunking. Positive slow wave (PSW) amplitudes increased as successive phonetically and semantically related items were presented, but they were observed earlier and were more prominent at Fz for semantic associates. PSWs at Fz and Cz also correlated with recall of semantic word chunks. This confirms prior claims that PSWs at Fz are potential markers of chunking which, in the proposed paradigm, were modulated differently from the detection of deviant stimuli and of relations between stimuli.

Social stress does not interact with paradoxical sleep deprivation-induced memory impairment.

Extensive evidence has linked both paradoxical sleep (PS) and stress to memory processing. The purpose of the present study was to examine the effect of social instability stress on memory and to verify whether this stress interferes with the amnesic effect of PS deprivation using the modified multiple platform method. In addition to the PS-deprived group (put onto narrow platforms inside the deprivation tanks) two control groups were used: one of them remained in its home-cages and the other was placed inside the deprivation tanks, onto a grid that contained large platforms on it. All groups were subdivided in socially stable and unstable conditions. Immediately after 96 h of sleep deprivation, the animals were trained in three different memory tasks: inhibitory avoidance, classical fear conditioning to a discrete stimulus and contextual fear conditioning. Twenty-four hours after training, the animals were tested in order to assess task acquisition. The results showed that social instability did not impair the performance of animals nor interacted with PS deprivation in any of the tasks. Grid control animals presented a selective impairment in the inhibitory avoidance task and contextual, but not in the classical, fear conditioning task, compared to cage control rats. This finding could be due to the stress to which grid control animals were exposed (humidity and luminosity) during the manipulation period. PS-deprived animals exhibited poorer performance than the other groups in all tasks. As they also showed an increased threshold to shock-induced vocalisation, but not to flinch response, it is not possible to completely rule out a decreased response to noxious stimulation as a contributing factor for the present results with PS deprivation.

Effects of dorsal striatum lesions in tone fear conditioning and contextual fear conditioning.

It has been suggested that the striatum mediates hippocampus-independent memory tasks. Classical fear conditioning to a discrete stimulus such as a tone is not affected by hippocampal lesion, whereas contextual fear conditioning is an hippocampus dependent task. The purpose of the present study was to verify the effect of dorsal striatal lesions on tone and contextual fear conditioning. The lesioned rats were not impaired in contextual fear conditioning but in tone fear conditioning both electrolytically and neurotoxically lesioned animals showed less freezing compared with controls. The lesion effect was observed after a postoperative recovery period of 14 days but not after 2 months. The results support the hypothesis that the dorsal striatum is involved in hippocampus-independent memory tasks, but, in spite of this involvement, it does not seem to be a critical structure.

Deficits in avoidance responding after paradoxical sleep deprivation are not associated with altered [3H]pirenzepine binding to M1 muscarinic receptors in rat brain.

Previous work had indicated that animals that were sleep-deprived and then trained on a passive avoidance task show poor retention of the task 24 h later after being allowed to sleep freely again. Cholinergic involvement is suggested by the fact that this effect is prevented by treatment with the muscarinic agonist pilocarpine during sleep deprivation. The observation that similar deficits are observed in non-deprived rats after treatment with M1-selective antagonist compounds such as dicyclomine or pirenzepine cause similar impairments, and gave rise to the hypothesis that sleep deprivation might induce significant reductions in M1 binding in brain areas involved in learning and memory processes. Rats were deprived of sleep for 96 h and then either immediately killed, or allowed to recover sleep for 24 h before being killed. [3H]pirenzepine binding to M1 sites was examined by quantitative autoradiography in 39 different brain areas in cage controls, sleep-deprived and sleep-recovered animals (N=8 per group). No significant differences among groups were found in any brain region. A separate group of animals was subjected to the sleep deprivation procedure and then trained in a simple avoidance task. Animals were then allowed to sleep and retested 24 h later. This group showed a significant impairment in the avoidance task compared to cage controls, in agreement with previous observations. These data suggest that proactive learning/memory deficits induced by sleep deprivation cannot be attributed to altered M1 binding either immediately after deprivation (when avoidance training occurs) or after sleep has recovered (when acquisition/retention are tested). The possibility remains that alterations in M1 function occur at post-membrane second messenger systems.

Flunitrazepam-induced changes in neurophysiological, behavioural, and subjective measures used to assess sedation.

INTRODUCTION: Certain features of event-related potentials (ERPs), electroencephalographic (EEG), and behavioural measures vary with differing states of alertness and/or sedation. PURPOSE: This study was conducted to investigate changes in several measures usually viewed as reflecting states of sedation/sleepiness associated with the use of a range of doses of the hypnotic benzodiazepine (BZD) flunitrazepam (FNZ). METHODS: This was a double blind, independent group design study of the effects of acute oral doses of FNZ in young healthy volunteers. Forty-eight subjects were randomly allocated to one of four groups-FNZ (0.6, 0.8, and 1.0 mg) and placebo (PLAC)-and tested prior to treatment and then in a posttreatment session close to the theoretical peak plasma concentration. ERP latencies and amplitudes were measured at midfrontal (Fz), midcentral (Cz), and midparietal (Pz) using a standard auditory oddball paradigm. EEG changes were assessed at Pz. Behavioural measures included the digit-symbol substitution test (DSST), a cancellation task (CT), and subjective ratings of alertness and attentiveness by the subjects (SUB) and the experimenter (EXP). RESULTS: FNZ led to psychomotor impairments and decreased alertness and attention; these effects were consistent with previous findings. A progressive, dose-related increase in P3 latency occurred in Fz, Cz, and Pz, and there was an increase in N1 (Fz, Cz) and N2 (Fz). N2-P3 amplitude decreased in Fz. EEG power bands beta 1 increased for the two highest doses, but no significant differences were noted in theta, delta, and alpha bands. P3 latencies, experimenter-rated levels of alertness, and DSST scores differentiated all three doses of FNZ from PLAC. CONCLUSION: The most sensitive measures used were P3 latencies of the ERPs (which varied with FNZ dose), DSST, and the experimenter-rated levels of alertness. However, we found no evidence for the assumption that one single phenomenon was reflected in all measures and different mechanisms were probably involved. Further experiments will be needed for more in-depth probing of the finer mechanisms underlying sedation/sleepiness and how they affect behavioural and eletrophysiological measures of the central nervous system (CNS) function.

Performance of university students on random number generation at different rates to evaluate executive functions.

OBJECTIVE: To evaluate the performance of adult young subjects in a Random Number Generation (RNG) task by controlling the response speed (RS). METHOD: Sixty-nine university students of both sexes took part in the experiment (25.05 +/- 6.71 year-old). Participants were alloted into 3 groups which differed in RS rates to generate numbers: 1, 2 and 4 seconds to generate each number. A digital metronomer was used to control RS. Participants were asked to generate 100 numbers. The responses were measured through Evans's RNG Index. RESULTS: There were statistically significant differences among the groups [F (3, 68) = 7.120; p <.05]. Differences were localized between 1 and 2 seconds (p = 0.004) and between 1 and 4 seconds (p = 0.006). No differences were observed between 2 and 4 seconds (p = 0.985). CONCLUSION: The present results suggest that the response speed in production of random numbers influences the performance of the Random Numbers Generation task.

A longitudinal study of a neuropsychological rehabilitation program in Alzheimer's disease.

UNLABELLED: Our aim was to study the duration of benefits derived from a neuropsychological rehabilitation program (NRP) for dementia patients. METHOD: The participants in this study were three patients diagnosed as probable Alzheimer's disease in the initial-to-moderate phase; the three were taking anticholinesterases. They were submitted to a neuropsychological evaluation (NE) before the NRP and then reevaluated after 12 and 24 months of treatment. The aim of our intervention was to do practical work with implicit and explicit residual memory by training them in everyday life activities, and using compensatory strategies and their intact cognitive abilities. RESULTS: Analysis of quantitative NE data (descriptive measures) after the first year of NRP showed cognitive improvement, functional stabilization and fewer behavioral problems. However, this improvement did not continue in the second year, and the disease maintained its characteristic progression.

[A comparative study of norms for a 400 picture set between Brazilian and American children]. / Um estudo comparativo das normas de um conjunto de 400 figuras entre crianças brasileiras e americanas.

OBJECTIVE: This study compared Brazilian and North American children regarding naming, familiarity and visual complexity of a set of 400 pictures. METHOD: Thirty-six Brazilian children (18 boys) aged 5 to 7 were evaluated. Their characteristics and the study procedure and measures were the same as those employed for the North American population enabling direct comparison of data from the two samples through Spearman rho correlations and Student t tests. RESULTS: Positive significant correlations between overall results of Brazilian and North American children were observed for all measures. Qualitative analysis showed that both groups gave modal names that differed from the intended names for the same 59 pictures. The Brazilian children named 72 pictures differently from the intended names that were correctly named by the North American children, who named 26 pictures differently from the intended names that were correctly named by the Brazilians. CONCLUSION: The 400 picture set was shown to be an adequate tool for use in different cultures. However, it is advisable to avoid pictures that produced naming inconsistencies by the Brazilian and North American children in studies in other cultures with the same age group until specific norms are made available.

Sensory processing abilities of children with ADHD.

OBJECTIVE: To assess and compare the sensory processing abilities of children with Attention Deficit/Hyperactivity Disorder (ADHD) and children without disabilities, and to analyze the relationship between sensory processing difficulties and behavioural symptoms presented by children with ADHD. METHOD: Thirty-seven children with ADHD were compared with thirty-seven controls using a translated and adapted version of the "Sensory Profile" answered by the parents/caregivers. For the ADHD group, Sensory Profile scores were correlated to behavioural symptoms assessed using the Child Behaviour Check List (CBCL) and the Behavioural Teacher Rating Scale (EACI-P). The statistical analyses were conducted using the Mann Whitney test and Pearson correlation coefficients. RESULTS: Children with ADHD showed significant impairments compared to the control group in sensory processing and modulation, as well as in behavioural and emotional responses as observed in 11 out of 14 sections and 6 out of 9 factors. Differences in all Sensory Profile response patterns were also observed between the two groups of children. Sensory Profile scores showed a moderately negative correlation with CBCL and EACI-P scores in the ADHD group. CONCLUSION: These results indicate that children with ADHD may present sensory processing impairments, which may contribute to the inappropriate behavioural and learning responses displayed by children with ADHD. It also suggests the importance of understanding the sensory processing difficulties and its possible contribution to the ADHD symptomatology.

Contrasting group analysis of Brazilian students with dyslexia and good readers using the computerized reading and writing assessment battery "BALE".

The analysis of cognitive processes underpinning reading and writing skills may help to distinguish different reading ability profiles. The present study used a Brazilian reading and writing battery to compare performance of students with dyslexia with two individually matched control groups: one contrasting on reading competence but not age and the other group contrasting on age but not reading competence. Participants were 28 individuals with dyslexia (19 boys) with a mean age of 9.82 (SD ± 1.44) drawn from public and private schools. These were matched to: (1) an age control group (AC) of 26 good readers with a mean age of 9.77 (SD ± 1.44) matched by age, sex, years of schooling, and type of school; (2) reading control group (RC) of 28 younger controls with a mean age of 7.82 (SD ± 1.06) matched by sex, type of school, and reading level. All groups were tested on four tasks from the Brazilian Reading and Writing Assessment battery ("BALE"): Written Sentence Comprehension Test (WSCT); Spoken Sentence Comprehension Test (OSCT); Picture-Print Writing Test (PPWT 1.1-Writing); and the Reading Competence Test (RCT). These tasks evaluate reading and listening comprehension for sentences, spelling, and reading isolated words and pseudowords (non-words). The dyslexia group scored lower and took longer to complete tasks than the AC group. Compared with the RC group, there were no differences in total scores on reading or oral comprehension tasks. However, dyslexics presented slower reading speeds, longer completion times, and lower scores on spelling tasks, even compared with younger controls. Analysis of types of errors on word and pseudoword reading items showed students with dyslexia scoring lower for pseudoword reading than the other two groups. These findings suggest that the dyslexics overall scores were similar to those of younger readers. However, specific phonological and visual decoding deficits showed that the two groups differ in terms of underpinning reading strategies.

Working memory screening, school context, and socioeconomic status: an analysis of the effectiveness of the working memory rating scale in Brazil.

OBJECTIVE: The study explores the psychometric properties of the Brazilian-Portuguese version of the Working Memory Rating Scale (WMRS-Br) in a population of 355 young children from diverse socioeconomic status and schooling backgrounds. METHOD: Public and private school teachers completed the WMRS-Br and children were assessed on a range of objective cognitive measures of fluid intelligence, working memory, and attention. RESULTS: Reliability and validity of the WMRS-Br were excellent across the public and private school sample. The WMRS-Br manifested substantial links with objective measures of working memory and medium links with selective attention, switching, and interference suppression. Confirmatory factor analyses suggest that a shorter version of the scale provides an adequate fit to the data. CONCLUSION: The WMRS-Br represents a valid screening tool in a Latin American context that has the potential to improve the early detection of working memory deficits in children growing up in poverty.

Attentional and executive functions are differentially affected by post-traumatic stress disorder and trauma.

BACKGROUND: Among the neurocognitive impairments observed in patients with Post-traumatic Stress Disorder (PTSD), attentional and executive dysfunctions appear to correlate with negative effects on education, work, daily life activities, and social relations, as well as the re-experiencing, avoidance, and hyperarousal symptoms of PTSD. However, there is no consensus regarding which aspects of attentional and executive functions are impaired in PTSD patients. METHODS: Attentional and executive functions were assessed using the digit span (WAIS-III) and spatial span (WMS-III) tests under forward and backward recall conditions, the Stroop Test, and the Wisconsin Card Sorting Test (WCST). Our sample was composed of victims of urban violence who developed PTSD (PTSD+) (n = 81), victims of urban violence who did not develop PTSD (PTSD-) (n = 70), and healthy controls not exposed to trauma (HC) (n = 50). RESULTS: The PTSD+ group had poorer performance on the spatial span forward subtest (p = 0.023; eta(2) = 0.038) and poorer execution time (p = 0.023; eta(2) = 0.042) and accuracy (p = 0.019; eta(2) = 0.044) on the Stroop Test compared to HC. CONCLUSIONS: These data suggest that there are few differences between the PTSD+ and HC groups, which are restricted to less complex measures of attentional and executive functional processes (short term capacity, selective attention, processing speed, and inhibitory control) and are related to visual stimuli. Therefore, cognitive impairments directly correlated with the manifestation of PTSD.

Executive functioning and reading achievement in school: a study of Brazilian children assessed by their teachers as "poor readers".

This study examined executive functioning and reading achievement in 106 6- to 8-year-old Brazilian children from a range of social backgrounds of whom approximately half lived below the poverty line. A particular focus was to explore the executive function profile of children whose classroom reading performance was judged below standard by their teachers and who were matched to controls on chronological age, sex, school type (private or public), domicile (Salvador/BA or São Paulo/SP) and socioeconomic status. Children completed a battery of 12 executive function tasks that were conceptual tapping cognitive flexibility, working memory, inhibition and selective attention. Each executive function domain was assessed by several tasks. Principal component analysis extracted four factors that were labeled "Working Memory/Cognitive Flexibility," "Interference Suppression," "Selective Attention," and "Response Inhibition." Individual differences in executive functioning components made differential contributions to early reading achievement. The Working Memory/Cognitive Flexibility factor emerged as the best predictor of reading. Group comparisons on computed factor scores showed that struggling readers displayed limitations in Working Memory/Cognitive Flexibility, but not in other executive function components, compared to more skilled readers. These results validate the account that working memory capacity provides a crucial building block for the development of early literacy skills and extends it to a population of early readers of Portuguese from Brazil. The study suggests that deficits in working memory/cognitive flexibility might represent one contributing factor to reading difficulties in early readers. This might have important implications for how educators might intervene with children at risk of academic under achievement.

Musicians' working memory for tones, words, and pseudowords.

Studies investigating factors that influence tone recognition generally use recognition tests, whereas the majority of the studies on verbal material use self-generated responses in the form of serial recall tests. In the present study we intended to investigate whether tonal and verbal materials share the same cognitive mechanisms, by presenting an experimental instrument that evaluates short-term and working memories for tones, using self-generated sung responses that may be compared to verbal tests. This paradigm was designed according to the same structure of the forward and backward digit span tests, but using digits, pseudowords, and tones as stimuli. The profile of amateur singers and professional singers in these tests was compared in forward and backward digit, pseudoword, tone, and contour spans. In addition, an absolute pitch experimental group was included, in order to observe the possible use of verbal labels in tone memorization tasks. In general, we observed that musical schooling has a slight positive influence on the recall of tones, as opposed to verbal material, which is not influenced by musical schooling. Furthermore, the ability to reproduce melodic contours (up and down patterns) is generally higher than the ability to reproduce exact tone sequences. However, backward spans were lower than forward spans for all stimuli (digits, pseudowords, tones, contour). Curiously, backward spans were disproportionately lower for tones than for verbal material-that is, the requirement to recall sequences in backward rather than forward order seems to differentially affect tonal stimuli. This difference does not vary according to musical expertise.

Influence of blood viscosity to cerebral blood flow in older humans compared to young subjects.

OBJECTIVE: Since blood viscosity (BV) is one of the most important factors determining blood flow, this study aimed to investigate the possible correlation between increased blood viscosity and reduction of regional cerebral blood flow (rCBF) in healthy ageing. METHODS: Male subjects were distributed in two groups: "young", aged 20-30 (27 volunteers), or "elderly", aged 60-70 (50 volunteers). Whole blood viscosity was obtained with a Wells-Brookfield Cone/Plate Viscometer. Cerebral blood flow was analysed by means of single photon emission computed tomography (SPECT). RESULTS: The mean BV values were 3.28±0.43 mPa in the group of young volunteers and 4.33±0.73 mPa in the group of elderly volunteers (t=-6.9, p<0.0001). The elderly had a lower blood flow than the young in the following regions: bilateral parietal; temporal-parietal and temporal of the left hemisphere. Pearson's correlation between BV and rCBF showed a good inverse correlation when the BV was above 3.95±0.83 mPa. CONCLUSIONS: Our results point to a close relationship between the two parameters analysed, BV and rCBF. The impairment in rCBF observed in the elderly volunteers might be due to an increase in BV, among other factors. SIGNIFICANCE: These findings suggest interesting possibilities for the treatment/prevention of brain ageing.

Reliability study of the Behavioral Assessment of the Dysexecutive Syndrome adapted for a Brazilian sample of older-adult controls and probable early Alzheimer's disease patients.

OBJECTIVE: Ecological tests are useful in assessing executive function deficits and may be of value in appraising response to treatment in Alzheimer's disease patients. Our aims were to examine executive function using the Behavioral Assessment of the Dysexecutive Syndrome for a Brazilian sample of older-adult controls and probable early Alzheimer's disease patients, and verify the applicability of this test battery. METHOD: Forty-one older-adult controls were matched with mild Alzheimer's disease patients by age, education, and gender. RESULTS: There significant inter-group differences in overall profile and almost all subtests except temporal judgment, time spent on planning the first and second Zoo Map visit, number of errors when copying drawings, naming pictures and Six Modified Elements arithmetic, and dysexecutive questionnaire self-rating. The Behavioral Assessment of the Dysexecutive Syndrome item that best discriminated controls from patients was the Modified Six Elements - adapted (general index), with a sensitivity of 80% and specificity of 90%, (AUC = 0.91, p < 0.001). CONCLUSION: Behavioral Assessment of the Dysexecutive Syndrome was effective in detecting executive function deficits in mild Alzheimer's disease patients, particularly the task switching, time monitoring, and rule-shift subtests.