Cognitive functioning in systemic lupus erythematosus: a meta-analysis.

Cognitive deficits are common in patients with systemic lupus erythematosus (SLE) regardless of overt neuropsychiatric involvement; however, a clear neuropsychological profile of SLE has not emerged. This study undertook a literature search of the PubMed, Scopus and Ovid (PsychINFO) databases for studies investigating cognitive alterations in SLE, using standardized neuropsychological (NP) measures. The data were analysed using meta-analytical procedures. The results support the observation that relative to healthy controls, SLE (regardless of overt neuropsychiatric involvement) is associated with statistically significant, small effect-sized deficits in visual attention, cognitive fluency, immediate visual memory and visual reasoning. Moreover, the results support a gradient of cognitive disturbance in SLE with significantly greater cognitive impairment in NPSLE patients relative to non-NPSLE patients. Medium-sized deficits were observed in NPSLE patients relative to healthy controls across the domains of: complex attention, delayed verbal memory, language and verbal reasoning (with small or non-significant differences observed in non-NPSLE patients relative to healthy controls). These results are relevant to the understanding, assessment and rehabilitation of patients living with SLE, with or without overt neuropsychiatric involvement.

The relationship between alcoholic cerebellar degeneration and cognitive and emotional functioning.

Although it is now widely acknowledged that the cerebellum contributes to the modulation of higher-order cognitive and emotional functions, this relationship has not been extensively explored in perhaps the largest group of individuals with cerebellar damage, chronic alcoholics. Localised damage to the cerebellum has been associated with a specific constellation of deficits and has been termed the 'cerebellar cognitive affective syndrome' (CCAS) [Schmahmann, J.D., Sherman, J.C., 1998. The cerebellar cognitive affective syndrome. Brain 121, 561-579]. The CCAS describes a profile of impairments, including deficits in executive functioning and visuospatial skills, language disruption and altered personality and affective behaviour. It is conceivable that the CCAS may also develop in a subgroup of alcoholics with alcoholic cerebellar degeneration and may in part account for a proportion of the cognitive and affective deficits commonly observed with the condition. While evidence has emerged supporting such a relationship, methodological limitations and the lack of theoretically driven investigation of the contribution of cerebellar dysfunction to cognitive and emotional functioning in chronic alcoholics, preclude definitive conclusions being drawn.

Facilitation and disruption of memory for the passive avoidance task in the day-old chick using dopamine D1 receptor compounds.

This series of studies provides a behavioural account of dopamine D1-receptor-dependent facilitation and disruption of memory for the single-trial passive avoidance task in the day-old chick. The D1 antagonist, SCH23390, induced memory disruption in a dose-dependent manner from 60 min after training with a strong (100% methyl anthranilate) aversant experience. The D1 agonist, SKF38393, was found to facilitate memory in chicks given a weak (20% vol/vol methyl anthranilate) training experience. The D2 antagonist, sulpiride, and the D2 agonist, quinpirole, showed no memory effects. The research indicates an important role for dopamine D1-dependent mechanisms in memory formation in the chick.

The effects of selective dopamine agonists on a passive avoidance learning task in the day-old chick.

Recent examination of the mixed dopamine agonist apomorphine suggests that dopamine inhibits both passive avoidance and response suppression learning. The present study investigated the effects of selective dopamine agonists on memory consolidation using a passive avoidance task in the day-old chick. The dopamine D1 agonist SKF 38393, the D2 agonist quinpirole, and the D4 agonist PD 168077 all failed to disrupt memory consolidation when injected immediately after training. However, chicks injected with 6.0 mg/kg of the D3 agonist (+)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) displayed memory impairment 180 min after aversive training. A study of the time course of this effect of 7-OH-DPAT showed that it first appeared 90 min after aversive training. Pretreatment with the dopamine D3 antagonist U 99194 eliminated the disturbance of passive avoidance learning induced by 7-OH-DPAT. These results indicate that dopamine is involved in the later stages of the memory formation process and that the D3 receptor is crucially involved in this disruption.

Alcohol consumption in the absence of adequate nutrition may lead to activation of the glyoxylate cycle in man.

The consumption of alcohol prior to food intake results in alcohol metabolism occurring in the liver, and the liver is often damaged in chronic alcoholics. This paper highlights the possibility that alcohol consumption in the absence of adequate nutrition after an extended period of time may lead to activation of the glyoxylate cycle, an energy pathway associated with the conversion of fat into carbohydrate which until recently was thought to only exist in plants and bacteria.

The effect of a moderate level of white wine consumption on the hypothalamic-pituitary-adrenal axis before and after a meal.

The nutritional status of the individual at the time of alcohol consumption may mediate the rate of alcohol absorption and metabolism, thus influencing the systemic effect of alcohol on the body. The aim in the present investigation was to assess the effect of moderate white wine consumption on the hypothalamic-pituitary-adrenal (HPA) axis under variable nutritional conditions. Seven males aged between 19 and 22 years participated in all aspects of the current investigation. The experimental procedure for the fasting trial required participants to ingest either 4 standard units of alcohol (40 g) or the equivalent amount of placebo over a 135-min period before consuming food for 45 min. Alternatively, in the feeding trial, food was consumed for 45 min prior to participants ingesting either 4 standard units of alcohol (40 g) or the equivalent amount of placebo over a 135-min period. Blood alcohol, salivary cortisol, and salivary dehydroepiandrosterone sulfate (DHEAS) levels were assessed at 45-min intervals during the 180-min experimental periods. The results demonstrated a significant alcohol-induced decrease in salivary cortisol irrespective of nutritional status and a significant decrease in salivary DHEAS when alcohol is consumed alone under fasting conditions only. It was concluded that moderate white wine consumption may promote a transient alteration in the functioning of the HPA axis.

The effects of apomorphine and haloperidol on memory consolidation in the day-old chick.

Apomorphine was found to disrupt memory consolidation in a dose-dependent manner on chicks trained on a 1-trial passive avoidance task with a strong aversant experience. Chicks injected with 4.0 mg/kg apomorphine displayed memory deficits at 180 min after learning and showed marked behavioral disturbances, including increased locomotion and increased pecking at the feet of conspecifics. Pretreatment with the dopamine antagonist haloperidol eliminated the memory disturbance induced by apomorphine and facilitated consolidation of memory in chicks given a weak (20% vol/vol methyl anthralinate) training experience. Time-of-retention data suggested that the memory disruption occurred from 120 min after learning, leading to the suggestion that dopamine-related modulation of the training experience may be involved in late-memory formation processes.

Lipopolysaccharide induces memory-processing deficits in day-old chicks.

Recent evidence has demonstrated that immune activation can result in cognitive deficits due to the actions of the proinflammatory cytokines. These series of studies examined the effects of peripheral administration of lipopolysaccharide (LPS) on the memory processes of day-old chicks trained on a single-trial passive-avoidance task. LPS impaired performance in a dose- and time-dependent manner. Maximal impairment was produced by a dose of 2.5-mg/kg LPS administered 60 min prior to training. Retention tests revealed that deficits in memory processing appeared between 10 and 20 min posttraining. These results demonstrate an inhibitory effect of LPS on memory processing at the transition point from short-term memory to intermediate-term memory.

Comparability of a single-trial passive avoidance learning task in the young chick across different laboratories.

The discrepant results noted by the La Trobe/Monash, Sussex, Open, and Berkeley University memory research groups employing the passive avoidance task (PAT) with the chick indicate that some of these differences may be due to differences in training procedures between the various groups. The procedures employed by each group were replicated as closely as possible and compared using the same strain of chick. Higher levels of pecking and lower training latencies were observed in the La Trobe/Monash chicks. Improved training latency was observed following a change in the day of experimentation with Sussex chicks, and in white light in Open chicks. A powerful reinforcing effect was observed when pretraining was conducted with a wet lure across multiple pretraining trials, indicating the importance of this difference between groups. The observed impact on chick performance of these variables indicates that differences between PAT procedures may have important interactive effects with aversive learning. The results of data gathered using different procedures may only be superficially comparable, and further investigation of the effects of these variables is indicated.

Hemispheric and gender-related differences in the gross morphology of the anterior cingulate/paracingulate cortex in normal volunteers: an MRI morphometric study.

The sulci and gyri found within the anterior cingulate (AC), and across the cerebrum generally, have been found to vary in location and complexity from one individual to the next, making it difficult to analyze imaging data accurately and systematically. In this study, we examined the nature of morphometric variance in the AC of the left and right cerebral hemispheres using high-resolution structural magnetic resonance imaging (MRI) acquired from 176 healthy volunteers. Depending on the presence of a paracingulate sulcus (PCS) and its antero-posterior extent, three types of AC patterns were identified: 'prominent', 'present' and 'absent'. Hemispheric comparisons across the whole sample showed the PCS to be more commonly 'prominent' in the left hemisphere and more commonly 'absent' in the right hemisphere. There was a significant gender difference, such that males showed an asymmetric pattern characterized by increased fissurization of the left AC, while females showed greater symmetry, with less fissurization of the left AC. Overall cerebral morphology, namely hemispheric volume and hemispheric fissurization, were also measured and used as independent variables as well as covariates in the analyses in order to ascertain the specificity of the results regarding AC morphology. Results showed that cerebral volume for males was larger on the right than on the left while fissurization showed the reverse asymmetry of greater leftward fissurization. In contrast, females were symmetric in both respects. The findings regarding AC morphology could not be explained by differences in these overall cerebral measures or by differences in age and handedness within the population. The results suggest that in the normal male brain, there exist morphological asymmetries at both the global and local levels that are less apparent in the female brain. The findings have implications for future studies examining the organization, development and functional anatomy of the AC.

The consequences of imbibing alcohol in the absence of adequate nutrition: the salt and water hypothesis.

Alcohol can have an effect on almost every cell in the human body and it is becoming increasingly clear that when alcohol is consumed the prior nutritional status of the individual may be an important factor for long-term health. The salt and water hypothesis integrates the biochemical findings from the current alcohol literature and proposes a mechanism by which alcohol consumption prior to food intake may cause a transient alteration in the functioning of the hypothalamic-pituitary-adrenal axis due to an alcohol-induced impairment in electrolyte regulation.

Modification of a weak learning experience by memory retrieval in the day-old chick.

Activation of memory retrieval after weak learning (WL), during either the short- or intermediate-term stages of memory in day-old chickens, resulted in the strengthening of the memory to levels normally associated with strong learning. Administration of the calcium channel antagonist lanthanum chloride, the glutamate receptor agonist monosodium glutamate, or the N-methyl-D-aspartate glutamatergic receptor antagonist AP5 prevented strengthening of a WL memory by reminder-activated memory retrieval. The results of this study are discussed in light of our recent findings suggesting two phases of memory retrieval in the day-old chick. The results are consistent with the proposition that a memory undergoing the processes of formation may be modified to include information gleaned at the time of memory retrieval and that a second phase of memory retrieval may be responsible for such modification.

Does the letter number sequencing task measure anything more than digit span?

A total of 102 undergraduate students performed the Letter Number Sequencing (LNS) task in addition to a series of other measures of reading, working memory, motor execution, visuo-spatial memory, and executive functions. Performance on the LNS was uniquely contributed to by reading level, digit span forward and backward, arithmetic, visual spatial learning, and by performance on the Symbol Search subtest of the WAIS-III. The results indicate that while much of the variance on the LNS task is explained by performance on the traditional measures of digit span, additional unique contributions to prediction of LNS performance are provided by measures of processing speed and visual spatial working memory.

A neuropsychological study of the postpolio syndrome: support for depression without neuropsychological impairment.

OBJECTIVE: This study aimed to examine cognitive functioning in postpolio syndrome (PPS) after controlling for the effects of depression and illness behavior. BACKGROUND: Few studies have investigated the possible cognitive sequelae of PPS, despite widespread documented subjective complaints of "mental fatigue." METHOD: A total of 23 PPS sufferers, 20 polio survivors without PPS, and 22 matched controls were compared using the Beck Depression Inventory-II; the Illness Behaviour Questionnaire; a chronic fatigue syndrome symptom checklist; and several measures of memory, attention, and concentration, including the Brown-Petersen Task, Stroop Test, Austin Maze, California Verbal Learning Test, Trail Making Test, Controlled Oral Word Association Test, and Symbol-Digit Modalities Test. RESULTS: In those participants with a medically confirmed diagnosis of PPS, there was a significantly higher level of depressive and hypochondriacal symptomatology as compared with the other two groups. Nevertheless, no significant differences existed between the three groups on neuropsychological measures. CONCLUSIONS: These results indicate that the attention and memory difficulties reported by PPS sufferers may be linked to the physical or psychological manifestations of the illness rather than to objective decrements in cognitive performance.

The role of the benzodiazepine-GABA system in the memory processes of the day-old chick.

This series of experiments investigated the effect of the benzodiazepine diazepam on memory formation in day-old chicks trained on a single-trial, passive-avoidance task. The findings indicate that diazepam has a dose-specific and time-dependent effect on memory processes. A 0.125-mg/kg dose of diazepam administered immediately after training led to amnesia in these subjects only after 30 min following learning. Pretreatment with bicuculline and flumazenil were effective in ameliorating the memory deficits caused by diazepam, and consolidated memory function in saline-treated controls following strong and weak aversant training. These findings suggest that benzodiazepine effects on memory are mediated by their effects on arousal, possibly by the release of noradrenaline, which is critical to the establishment of long-term memory.

Differentiation of dementia of the Alzheimer's type from depression with cognitive impairment on the basis of a cortical versus subcortical pattern of cognitive deficit.

This study compared 15 "mildly" cognitively impaired participants with Dementia of the Alzheimer Type (DAT), 15 depressed cognitively impaired participants (DCI), and 15 normal participants. The participants were matched for age, and reading ability, and were tested on a series of cognitive instruments selected on the basis of their ability to distinguish a cortical versus subcortical pattern of deficit. The DAT group demonstrated impaired performances on tests of language, praxis and gnosis. Deficits in these areas were absent from DCI group. There were differences between all of the groups on the California Verbal Learning Test, but after this effect was controlled using an analysis of covariance procedure, the differences in tests of gnosis, praxis and language function between the DCI and the DAT participants still remained. These findings support the clinical usefulness of the cortical-subcortical distinction in differentiating DCI from DAT.

A comparison of cognitive performance in binge versus regular chronic alcohol misusers.

One hundred cases of individuals assessed for alcohol-related cognitive performance were examined. The assessment included demographic and alcohol consumption data, as well as performance on tests of auditory verbal learning, memory, motor skills, general intellectual functioning, and visuospatial functioning. All participants regularly drank in excess of 10 standard drinks/session. Fifty cases were binge drinkers who consumed alcohol on 2 days/week or less and 50 cases were individuals who consumed alcohol daily. The two groups of drinkers were statistically matched on a number of demographic and misuse factors. The results indicated similar performance for both the binge drinkers and the regular drinkers in visuo-motor speed, visuo-spatial organization and planning, learning, proactive interference, retroactive interference, and retrieval efficiency. However, performance differences were observed on tasks that required semantic organizational ability, with binge drinkers performing better than regular drinkers on these tasks. Due to the differences in the cognitive performance of the two groups, it was concluded that drinking pattern is an important factor in investigating cognitive performance in alcoholics.

The role of imagery in sexual arousal disturbances in the male traumatically brain injured individual.

Over 50% of individuals who suffer traumatic brain injury (TBI) demonstrate a decrease in sexual arousal post-injury. This study investigated the basis of this loss and hypothesized that it occurred as a consequence of the effect of the injury on cognition: specifically, diminution of the ability to form and manipulate sexually arousing imagery. The study compared 14 male participants who identified themselves as having alteration in sexual functioning following traumatic brain injury with a further 14 non-brain injured participants, case matched to them for age and education. All TBI participants were assessed after 2 years following injury, and had had a loss of consciousness of 3 days or greater. The results indicated that the two groups differed in terms of their performance on the Bett's QMI Scale, the Gordon Test of Visual Imagery Control, the Vividness of Sexual Imagery Scale of the Imaginal Processes Inventory, the State Trait Anxiety Inventory, and the Beck Depression Inventory. After correction for the level of depression by analysis of covariance, the TBI participants still featured lower levels of performance on the Sexual Imagery sub-scale of the Imaginary Processes Inventory. The results indicate that sexual arousal disturbances may exist above and beyond the disturbances to affect associated with the psychosocial effects of the TBI.

The cognitive determinants of performance on the Austin Maze.

This study aimed to investigate which abilities are measured by the Austin Maze. One hundred and eight university students were administered a battery of eight neuropsychological tests including, the Austin Maze, the Tower of London, the Wisconsin Card Sort Test, Block Design, the Visual Spatial Learning Test, Digit Span Backwards, the Brown-Peterson Task and the Wide Range Achievement Test of Reading. Results indicated that visuospatial ability and memory both significantly contributed to performance on the Austin Maze, but differed in the degree to which they explained the performance depending on which measure of maze performance was employed. It appears that visuospatial ability is measured in early trials of the Austin Maze when individuals are orienting themselves to the path. In later trials individuals must call upon visuospatial memory to consolidate the details of the path. Executive function and working memory were not found to be significantly implicated in performance on the Austin Maze.

Decrease in performance on the verbal fluency test as a function of time: evaluation in a young healthy sample.

Participants were asked to generate as many words as possible using large and small category sizes with the initial letter and semantic category search strategies. The production of each participant for each 15-s time slice on each task was recorded. The results revealed that on all fluency tasks, the production in the initial time slice was highest and also of greatest frequency. As time on task increased the production decreased, as did the word frequency of the items produced. The results are consistent with the notion that there is a store of high-frequency words accessed during the early trials of the fluency tasks and as this store becomes exhausted the production and the word frequency decreases.