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A thorough understanding of the relationship between cognitive test performance and symptoms of depression, anxiety, or post-traumatic stress disorder (PTSD) in people with traumatic brain injury (TBI) is important given the high prevalence of these emotional symptoms following injury. It is also important to understand whether these relationships are affected by TBI severity, and the validity of test performance and symptom report. This meta-analysis was conducted to investigate whether these symptoms are associated with cognitive test performance alterations in adults with a TBI. This meta-analysis was prospectively registered on the PROSPERO International Prospective Register of Systematic Reviews website (registration number: CRD42018089194). The electronic databases Medline, PsycINFO, and CINAHL were searched for journal articles published up until May 2020. In total, 61 studies were included, which enabled calculation of pooled effect sizes for the cognitive domains of immediate memory (verbal and visual), recent memory (verbal and visual), attention, executive function, processing speed, and language. Depression had a small, negative relationship with most cognitive domains. These relationships remained, for the most part, when samples with mild TBI (mTBI)-only were analysed separately, but not for samples with more severe TBI (sTBI)-only. A similar pattern of results was found in the anxiety analysis. PTSD had a small, negative relationship with verbal memory, in samples with mTBI-only. No data were available for the PTSD analysis with sTBI samples. Moderator analyses indicated that the relationships between emotional symptoms and cognitive test performance may be impacted to some degree by exclusion of participants with atypical performance on performance validity tests (PVTs) or symptom validity tests (SVTs), however there were small study numbers and changes in effect size were not statistically significant. These findings are useful in synthesising what is currently known about the relationship between cognitive test performance and emotional symptoms in adults with TBI, demonstrating significant, albeit small, relationships between emotional symptoms and cognitive test performance in multiple domains, in non-military samples. Some of these relationships appeared to be mildly impacted by controlling for performance validity or symptom validity, however this was based on the relatively few studies using validity tests. More research including PVTs and SVTs whilst examining the relationship between emotional symptoms and cognitive outcomes is needed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

While a significant proportion of the population suffer from migraine, the existing research literature does not provide a clear indication as to whether migraineurs experience objective cognitive deficits outside of acute migraine attacks. This meta-analysis was conducted to investigate which cognitive domains if any were affected by migraine, by synthesising the existing research quantitatively. The meta-analysis was prospectively registered with the PROSPERO International prospective register of systematic reviews (registration no.: CRD42019134138). A search of the electronic databases PubMed, Ovid MEDLINE, and PsycINFO was conducted for journal articles published between January 1980 and January 2020. Seventeen studies met the inclusion criteria, allowing for the calculation of pooled effect sizes between migraineurs (with and without aura) and healthy controls in the several cognitive domains. During the interictal period, migraineurs demonstrated a moderate, negative effect on complex attention immediate and delayed memory, spatial cognition, and executive functioning. This effect was not attributable to migraine history, attack frequency, or participant age. However, the lack of performance validity testing, and limited data on mood symptomatology and migraine medication use in the included studies may be confounds potentially overestimating the magnitude of effect. Comparison with a clinical control group, which may have accounted for some these extraneous variables, was unable to be conducted. Recommendations for comprehensive future neuropsychological research are provided., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study examined the relative contribution of performance and symptom validity in litigating adults with traumatic brain injury (TBI), as a function of TBI severity, and examined the relationship between self-reported emotional symptoms and cognitive tests scores while controlling for validity test performance., Method: Participants underwent neuropsychological assessment between January 2012 and June 2021 in the context of compensation-seeking claims related to a TBI. All participants completed a cognitive test battery, the Personality Assessment Inventory (including symptom validity tests; SVTs), and multiple performance validity tests (PVTs). Data analyses included independent t-tests, one-way ANOVAs, correlation analyses, and hierarchical multiple regression., Results: A total of 370 participants were included. Atypical PVT and SVT performance were associated with poorer cognitive test performance and higher emotional symptom report, irrespective of TBI severity. PVTs and SVTs had an additive effect on cognitive test performance for uncomplicated mTBI, but less so for more severe TBI. The relationship between emotional symptoms and cognitive test performance diminished substantially when validity test performance was controlled, and validity test performance had a substantially larger impact than emotional symptoms on cognitive test performance., Conclusion: Validity test performance has a significant impact on the neuropsychological profiles of people with TBI, irrespective of TBI severity, and plays a significant role in the relationship between emotional symptoms and cognitive test performance. Adequate validity testing should be incorporated into every neuropsychological assessment, and associations between emotional symptoms and cognitive outcomes that do not consider validity testing should be interpreted with extreme caution., (© The Author(s) 2022. Published by Oxford University Press.)

Topographical disorientation is the impairment or inability to successfully navigate in three-dimensional space. Differing topographical disorientation syndromes have been associated with distinct lesion sites in the acquired brain injury (ABI) literature. This meta-analysis attempted to investigate the relationship between lesion location and dysfunctions in specific navigational abilities resulting in topographical disorientation in individuals with ABI, as measured by their performance on experimental and neuropsychological tests. It was expected that focal lesions would be associated with a specific navigational deficit in one ability, with relative sparing of other navigational abilities. Twenty-six papers met the inclusion criteria for the analysis. Results indicated that ABI populations performed worse on all measures of navigation, with moderate to large effect sizes. Dysfunctions in three core navigational skills were consistent with the available lesion studies: a feature/landmark processing unit, a spatial processing unit, and a spatial/feature binding and associative learning unit. A sequential processing model was created to attempt to best represent the transfer of information between these units and the process by which navigational knowledge is generated. The model was then used to assess the validity of existing models of navigation and topographical disorientation.

This meta-analysis examined how performance on various cognitive domains of neuropsychological functioning can contribute to predicting progression to dementia from mild cognitive impairment (MCI) or subjective memory complaints. Studies performed between the years of 1997 and 2018 were identified through a search of the electronic databases Medline and PsycINFO. Data from the articles identified were pooled to determine standardized mean differences, calculated as Hedges g, using a random-effects model. Twenty-four studies were included in the analysis. The majority of studies examined the progression of amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD). Nonprogressors performed significantly better than did progressors in the domains of divided attention, executive function, expressive language, immediate recall, processing speed, delayed recall, visuospatial/constructional ability, working memory, and sustained attention. These findings indicate that individuals with MCI or subjective memory complaints who do not progress to dementia, perform better at baseline as compared with individuals that progress to dementia on a range of neuropsychological measures, and lends further support to the contention that neuropsychological assessment can make important contributions to predicting progression to dementia while individuals are still in the MCI or subjective memory complaint stage. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

A thorough understanding of the cognitive effects of corticosteroids is essential given their frequency of use. This meta-analysis was conducted to investigate the effects of corticosteroids on the various domains of cognitive functioning, grouped by duration of use. An electronic search of PsycInfo, Medline and Google Scholar was conducted for all journal articles published between January 1990 and May 2018. Twenty six studies were included enabling calculation of standardised mean difference (SMD) using a random effects model for the cognitive domains of divided attention, executive function, expressive language, immediate memory, processing speed, recent memory, sustained attention, very long term memory and working memory. Results revealed that corticosteroids had a modest, negative effect on executive function for acute users, recent memory for short term and chronic users, and very long term memory for acute users. Corticosteroids had a small, significant, positive effect on expressive language for short term users.

Objectives: The aim of this study was to compare the two most commonly prescribed classes of atypical antipsychotic medications (i.e., -pines and -dones) with regard to their effects on cognition in patients with schizophrenia., Data Sources: Ovid Technologies web-based software was used to search the Medline and PsycINFO computerized databases to identify articles that met the inclusion criteria., Review Methods: The search was limited to papers published after 1990, written in English, employing human subjects, using atypical antipsychotics, using a within-subjects design or control group of patients with schizophrenia for comparisons, using participants aged from 18-65, and employing standardized neuropsychological measures., Results: A total of 996 eligible studies were identified, and of these 19 were finally analyzed. Nine domains of cognitive functioning were assessed. The two groups of agents produced equivalent overall effects (-dones = .254 versus -pines = .202). The -pines were found to improve the domains of attention/working memory, executive functioning, fluency, nonverbal memory, processing speed, and verbal memory, each with a significant, small effect size. The -dones were found to improve attention/working memory, executive functioning, motor function, nonverbal memory, processing speed, and verbal memory, each with a significant, small effect size. Failsafe N was robust for all of the domains for the -pines, but only for the verbal memory domain for the -dones, suggesting that the significant findings for the other domains with the -dones are more tenuous., Conclusion: The results indicate that the agents were largely equivalent and that there was no clear evidence that the pattern of cognitive effects differed as a result of the agent applied. The effects themselves, while statistically significant, were small, indicating that some or all of the differences may be attributable to practice effects on the instruments employed.

Objective: This study presents an updated meta-analysis replicating the study of (Stavro, K., Pelletier, J., & Potvin, S. (2013). Widespread and sustained cognitive deficits in alcoholism: A meta-analysis. Addiction Biology, 18, 203-213. doi:10.1111/j.1369-1600.2011.00418.x) regarding the cognitive functioning of alcoholics as a function of time abstinent., Methods: A total of 34 studies (including a total of 2,786 participants) that met pre-determined inclusion and exclusion criteria were included in the analyses. The alcoholics were categorised into recently detoxified alcoholics (0-31 days sober), alcoholics 32-365 days sober and alcoholics >365 days sober consistent with the previous study. The current study employed more stringent control on the tests included in the analysis to include only those tasks described in contemporary neuropsychological test compendia. Forty-seven percent of the papers surveyed were not include in the previous meta-analysis., Results: The results indicated that there was a diffuse and pervasive pattern of cognitive deficit among recently detoxified alcoholics and that these deficits, particularly with regard to memory functioning, persisted even in longer term abstinent alcoholics. This was inconsistent with the prior meta-analysis which contended that significant cognitive recovery was possible after as little as 1 year., Conclusion: The persisting cognitive deficits were noted across a wide range of cognitive functions, supporting the notion of a diffuse rather than a specific compromise of cognition in alcoholism following discontinuation, as measured using standardised neuropsychological tests. Limitations on the finding included the fact that it was a cross-sectional rather than a longitudinal analysis, was subject to heterogeneity of method, had low representation of females in the samples, and had fewer studies of long-term sober samples., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study presents an updated meta-analysis of the effects of benzodiazepines on cognitive functioning in long-term, current users of these agents, those who have recently withdrawn and on those who have successfully abstained following withdrawal. The study represents an update of the previous meta-analyses published by our group., Method: A comprehensive search of the computerized databases Medline and PsycINFO was undertaken to identify studies that assessed the cognitive effects of benzodiazepines published up to 28 November 2016 (the date of the last update). Nineteen studies (eight studies published since the previous meta-analyses and 11 studies included in the previous studies) were included., Results: The results of the analysis for current users revealed statistically significant, negative effects for the cognitive domains of working memory, processing speed, divided attention, visuoconstruction, recent memory, and expressive language. For those who had withdrawn and successfully abstained following withdrawal, deficits were observed for the domains of recent memory, processing speed, visuoconstruction, divided attention, working memory, and sustained attention., Conclusions: The results of the study are important in that they corroborate the mounting evidence that a range of neuropsychological functions are impaired as a result of long-term benzodiazepine use, and that these are likely to persist even following withdrawal. The findings highlight the residual neurocognitive compromise associated with long-term benzodiazepine therapy as well as the important clinical implications of these results.

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.

Background: Carbon monoxide (CO) poisoning is the leading cause of accidental poisoning worldwide. This study undertook a meta-analysis to examine differences in neuropsychological functioning in patients with CO poisoning as compared to healthy controls, and examined the longer-term neuropsychological effects of CO poisoning., Methods: Studies performed between the years 1995 and 2016 were identified through a search of the electronic databases Medline and PsycInfo. Data from the papers identified were pooled to determine standard mean differences using a random-effects model., Results: Ten studies were included in the analysis, with healthy controls performing significantly better than CO poisoned participants on the domains of divided attention, immediate memory, and processing speed. No statistically significant differences were found for sustained attention, recent memory, working memory, visuospatial/constructional ability, and expressive language. Performance by participants with CO poisoning for the domains of sustained attention, recent memory, visuospatial/constructional abilities, and working memory significantly improved over time after initial exposure, demonstrating recovery of these functions over time. No statistically significant differences were evident for divided attention or expressive language., Conclusions: This evidence indicates that healthy controls perform better than do individuals with CO poisoning on a range of neuropsychological domains; however, it also indicates that performance in some domains does improve over time. (JINS, 2018, 24, 405-415).

Objective: Neuropsychological assessment (NPA) addresses important aspects of diagnosis, prognosis, treatment, and rehabilitation planning. This review set out to determine the impact of NPA on the adult patient's outcome, by examining how and whether NPA influences diagnostic decision-making and surgical planning, how NPA can be used to predict patient outcome, and how clients, referrers, and significant others perceive the value of NPA., Method: Eligible studies were selected according to pre-defined selection criteria and accessed via the electronic databases Medline and PsycInfo., Results: Eighty-one studies were included, with 14 examining the influence of NPA on diagnosis, 62 in predicting outcomes, and 5 addressing the perceptions of NPA by users. The evidence was generally supportive of the value of NPA for its ability to increase the accuracy of diagnoses, to assist with decisions regarding surgical planning, to predict patient outcomes, and in its clinical benefit as reported by physicians and patients., Conclusion: The review demonstrated the benefit of NPA in assisting with diagnosis and prognosis, and showed positive findings with regard to consumer perceptions of NPA. The neuropsychological literature would materially benefit from high-quality randomized control trials of NPA to definitively demonstrate the efficacy of this measure in clinical management.

A thorough understanding of the cognitive effects of antidepressant medications is essential given their frequency of use. This meta-analysis was conducted to investigate whether antidepressants differentially affect the various domains of cognitive functioning for depressed and non-depressed participants. An electronic search of PsycInfo, Medline and Google Scholar was conducted for all journal articles published between January 1998 and January 2017. Thirty-three studies were included enabling calculation of Hedges' g using a random effects model for the cognitive domains of divided attention, executive function, expressive language, immediate memory, perceptual motor skills, processing speed, recent memory, sustained attention, visuospatial-constructional skills and working memory. Results revealed that overall, antidepressants have a modest, positive effect on divided attention, executive function, immediate memory, processing speed, recent memory and sustained attention for depressed participants. Selective serotonin reuptake inhibitors (SSRI's) were found to have the greatest positive effect on cognition for depressed participants, as compared to the other classes of antidepressants analysed. Antidepressants did not significantly affect cognitive function in non-depressed participants.

Shame and guilt are closely related self-conscious emotions of negative affect that give rise to divergent self-regulatory and motivational behaviours. While guilt-proneness has demonstrated positive relationships with self-report measures of empathy and adaptive interpersonal functioning, shame-proneness tends to be unrelated or inversely related to empathy and is associated with interpersonal difficulties. At present, no research has examined relationships between shame and guilt-proneness with facial emotion recognition ability. Participants (N = 363) completed measures of shame and guilt-proneness along with a facial emotion recognition task which assessed the ability to identify displays of anger, sadness, happiness, fear, disgust, and shame. Guilt-proneness was consistently positively associated with facial emotion recognition ability. In contrast, shame-proneness was unrelated to capacity for facial emotion recognition. Findings provide support for theory arguing that guilt and empathy operate synergistically and may also help explain the inverse relationship between guilt-proneness and propensity for aggressive behaviour.

This meta-analysis set out to ascertain the cognitive function of obstructive sleep apnea (OSA) patients as measured through objective neuropsychological tests. The meta-analysis investigated the cognitive functioning of these patients prior to them receiving any treatment such as continuous positive airway pressure (CPAP). A total of 19 studies met the study inclusion criteria. Results revealed statistically significant negative effect sizes in the cognitive domains of non-verbal memory, concept formation, psychomotor speed, construction, executive functioning, perception, motor control and performance, attention, speed of processing, working and verbal memory, verbal functioning and verbal reasoning. The clinical implication of these results, the possible causal mechanisms of the cognitive impairments and the implication of these for future research were each discussed. Despite a number of important limitations, the analysis highlights the need for clinicians to comprehensively explore complaints about sleep disturbance, particularly OSA, in all clinical assessments to ensure control for this important confounder in order to ensure appropriate attribution of the source of any observed cognitive compromise., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: This study investigated proactive and retroactive interference effects between the Wechsler Memory Scale-Fourth Edition (WMS-IV) using the flexible approach, and the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV)., Method: One hundred and eighty nonclinical participants were assigned to a four (visual interference, verbal interference, visual and verbal interference, vs. no interference) by two (retroactive vs. proactive) between-subjects design. The administration order of the tests was counterbalanced (i.e., administration of the WAIS-IV prior to the WMS-IV, and the WAIS-IV administered during the delay interval of the WMS-IV)., Results: The WAIS-IV produced significant retroactive interference effects on the WMS-IV; however, no proactive interference effect was observed. The retroactive interference effect was dependent on material specificity., Conclusions: The results indicate that material presented within the delay of the WMS-IV can have a significant effect on subsequent delayed recall. Clinicians should carefully consider the effects associated with carry-over effects of these tests when using them in combination.

The Boston Naming Test (BNT) (Kaplan, Goodglass, & Weintraub, 1983) is the most commonly used test of confrontation naming in neuropsychology (Rabin, Barr, & Burton, 2005). However, there are significant criticisms of the BNT which suggest that it might not be the assessment measure of choice. These criticisms are that the BNT has poor psychometric properties, is not adequately standardized, and has inadequate norms. It is further suggested that when considered in the context of contemporary conceptualizations of the neuropsychology of naming, the BNT does not adequately capture the processes known to be required for successful naming, and does not sample widely enough from the content domain of "naming". These criticisms suggest that the BNT is flawed as a measure of naming, and are discussed in detail in this review. Other stand-alone visual confrontation naming tasks are reviewed to evaluate whether any might be viable substitutes for the BNT in clinical neuropsychology. The Naming Test from the Neuropsychological Assessment Battery (Stern & White, 2009) was identified as a possible alternative to the BNT, however, neither of these tests was designed with reference to models of the neuropsychology of naming, and development of a new test of naming is indicated.

The "z-drugs" zopiclone, zolpidem, eszopiclone, and zaleplon were introduced in the 1980s for the treatment of insomnia, as it was observed that the side effect profile associated with these medications were more benign than those related to the benzodiazepines. This meta-analysis set out to ascertain which domains of cognitive function, if any, were affected by the ingestion of these medications. A total of 20 studies met the study inclusion criteria. Results revealed medium effect sizes for zopiclone and zolpidem on measures of verbal memory. An additional medium effect size was observed for zolpidem on attention. Finally, smaller effect sizes were observed for zolpidem speed of processing and for zopiclone on working memory. It is clear from these data that the use of a single dose of the z-drugs in healthy adults as measured in the morning following the exposure does produce a specific rather than a generalized negative effect on cognitive function. However, there were only enough studies to evaluate the individual cognitive effects of the zolpidem and zopiclone medications; the specific effects of zaleplon and eszopiclone cannot be ascertained because only one study met the inclusion and exclusion criteria for the review.

It is now widely accepted that in addition to motor coordination, the cerebellum is also involved in the modulation of cognitive and affective processes. Despite alcoholic cerebellar degeneration (ACD) being the most common form of cerebellar disorder, little systematic investigation of cerebellar-mediated cognitive and affective deficits has occurred in chronic alcoholics. Forty-nine chronic alcoholics and 29 healthy control participants underwent testing of cognitive and affective function, along with measurement of cerebellar ataxia using the International Cooperative Ataxia Rating Scale (Trouillas et al., Journal of the Neurological Sciences 145:205-11, 1997). The alcoholic group demonstrated significantly poorer performance as compared to the control group in a number of domains, including visuospatial and language skills, psychomotor speed, new learning and memory, executive functioning, and emotional regulation and affect processing. There were no differences between the alcoholic and control groups in immediate attention and working memory abilities. Years of heavy drinking and total period of abstinence were found to be the best predictors of cognitive and emotional function in the alcoholic group. After accounting for alcohol chronicity, there was still a relationship between the degree of clinical signs of ACD and some areas of cognitive and emotional functioning, including language, executive functioning, processing speed and affect processing. The results suggest that some of the cognitive and affective deficits observed in chronic alcoholics may be mediated, at least in part, by cerebellar dysfunction. These findings add support to the theory of disruption to bidirectional cerebro-cerebellar circuitry underlying cognitive and affective deficits in chronic alcoholics.

The Balloon Analogue Risk Task (BART) is an experimental measure of risk taking that has commonly been employed to measure the risk taking behavior of nonclinical populations. Previous research has indicated that the task measures a unique aspect of behavioral disinhibition, but there has not as yet been focus upon the possible impact of other aspects of cognitive processing on performance. The current study investigated the cognitive factors related to performance of the BART in an alcohol-using sample. Seventeen individuals with long-term alcohol use were matched for age and education to a group of 17 nonusing participants. The results indicated that the alcohol-using group pumped the balloons on the BART to a lesser extent than did the nonusing group across all trials on the task. The results indicate that the alcohol-using group made less "optimal" decisions on the BART most notably due to neuropsychological impairment in the domains of immediate memory and executive functioning.

Dispute has surrounded the issue of whether the relationship between anosmia and executive dysfunction in traumatic brain injury (TBI) may be artefactual due to poor ascertainment. Three groups matched for age, gender, education, Full Scale IQ, and the Wechsler Working Memory Index and showing adequate symptom validity were compared: 30 anosmic TBIs (TBI-A) matched for posttraumatic amnesia (PTA) and working memory functioning with 36 nonanosmic TBIs (TBI-NA) and 51 controls. The groups performed the FAS test, the Animal Fluency test, the Stroop Neurological Screening Test (SNST), the Wisconsin Card Sorting Test-64 (WCST-64) and the Trail Making Test (TMT-B) as well as tests of emotional functioning and return to work outcome. After adjusting for the covariates (i.e., gender; Wechsler Test of Adult Reading, WTAR; and years of education), a significant effect was found for items successfully completed on the SNST, the FAS task, the Animal Fluency task, and the WCST-64 categories completed. After adjusting for the covariates, a significant difference was found for number of errors on the SNST and for the number and type of errors on TMT-B. The two groups did not differ in terms of their affective functioning (i.e., Beck Depression Inventory or Beck Anxiety Inventory), or in terms of their outcome with regard to return to work. The findings support the notion that the TBI-A group demonstrated considerably weaker performance on executive tasks than did the nonanosmic TBIs. These patients were not, however, more prone to an error-prone pattern of performance, and, if anything, their executive deficit was more likely attributable to a reduced productivity of response.

Piracetam is an AMPAkine drug that may have a range of different mechanisms at the cellular level, and which has been shown to facilitate memory, amongst its other effects. This series of experiments demonstrated that a 10mg/kg dose of piracetam facilitated memory consolidation in the day-old chick when injected from immediately until 120min after weak training (i.e. using a 20% v/v concentration of methyl anthranilate) with the passive avoidance learning task. Administration of piracetam immediately after training led to memory facilitation which lasted for up to 24h following training. This dose of the AMPAkine was not shown to facilitate memory reconsolidation. These findings support the contention that application of the AMPAkine piracetam facilitates memory using a weak training task, and extend the range of actions previously noted with NMDA-related agents to those which also facilitate the AMPA receptor., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Alcoholism is the most common cause of cerebellar dysfunction, yet estimates of the incidence of alcoholic cerebellar degeneration (ACD) vary greatly, with differences in methodologies contributing to these disparate findings. This study set out to characterize the frequency and pattern of clinical signs of ACD in an alcoholic group using the International Cooperative Ataxia Rating Scale (ICARS)., Methods: We compared the performance of 49 alcoholics and 29 control participants. The relative contributions of demographic and alcohol consumption variables to ICARS scores in the alcoholic group were also examined., Results: The alcoholic group demonstrated significantly poorer performance on all of the ICARS subscales as compared with the control group. Within the alcoholic group, performance was more impaired on the speech scale than on all of the other scales, except the lower limb component of the kinetic scale, and less impaired on the oculomotor scale compared with all other scales. Years of heavy drinking and lifetime alcohol consumption correlated with total ICARS scores; however, maximum daily consumption was actually negatively correlated with ICARS scores. Of the alcohol history variables, years of heavy drinking was the best predictor of total ICARS scores, making a 19% unique contribution, followed by the period of abstinence from alcohol, which uniquely contributed 7% of the variance. There were high correlations between age and male gender and the alcohol consumption variables; however, age and gender were still found to uniquely contribute 5 and 7% respectively to the variance in total ICARS scores., Conclusions: ACD may affect up to two-thirds of chronic alcoholics. Assessing the number of years an individual has been drinking beyond a certain threshold can give a good indication of the likelihood of ACD. Age, gender, and the source of the clinical sample may significantly contribute to the prevalence of ACD and require further detailed investigation., (Copyright © 2012 by the Research Society on Alcoholism.)

Recent research has pointed to a role for brain-derived neurotrophic factor (BDNF) in long-term potentiation and memory. The present series of experiments examined the effects of the application of exogenous BDNF on memory consolidation and reconsolidation of a weak training stimulus with the day-old chick, using the passive avoidance learning paradigm. Chicks injected intracranially with 12.5 μg/mL recombinant BDNF immediately after a single-trial training event displayed enhanced retention relative to saline up to 24h post-training. Furthermore, this dose was also shown to enhance retention when administered following initial weak training. Thus, exogenous BDNF was shown to enhance both consolidation and reconsolidation of memory when administered acutely to the day-old chick., (Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.)

Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist that has been approved for the treatment of the cognitive deficits noted in Alzheimer's disease. While there is a body of research that supports memantine's facilitative action upon memory compromise, this series of studies aimed to investigate the effects of this drug in healthy animals with intact memory functioning. A 0.1 mM dose of memantine injected immediately after a weakly aversive training event (i.e. 20% v/v methyl anthranilate) was found to enhance passive avoidance learning for this event in day-old chicks up to 24 h following training. The same dose of memantine was also observed to enhance memory for the training event when it was administered in conjunction with a reminder trial. These results suggest that memantine is capable of facilitating both memory consolidation as well as memory reconsolidation. It was concluded that memantine's mechanism may involve the short-term or intermediate memory phases of the Gibbs and Ng model of memory, and that the current findings represent enhancement of intact memory, rather than amelioration of memory compromise., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

This study investigated episodic and procedural memory performance in early and late pregnancy. Twenty-six women in the third trimester of pregnancy, 20 women in the first trimester of pregnancy, and 24 nonpregnant controls were administered a battery of verbal and visual episodic memory tasks and two procedural memory tasks. Results indicated that compared to controls, both pregnant groups had reduced scores on immediate and delayed verbal episodic memory tasks, but were unimpaired on visual and procedural memory tasks. Verbal memory differences could not be accounted for by mood state or attention; however, progesterone level accounted for a small amount of the variation. Although memory differences were minor, the perception of memory problems may have implications for everyday living for pregnant women.

Background: Anecdotal reports of sleep disturbance during pregnancy are abundant; however, objective measurement of sleep changes has so far produced conflicting results., Aims: To objectively measure sleep architecture and investigate subjective sleep quality in the first and third trimester of pregnancy, when compared to the nonpregnant state., Methods: Twenty-seven women in the third trimester of pregnancy, 21 women in the first trimester of pregnancy and 24 nonpregnant control women underwent overnight polysomnography and completed questionnaires regarding sleep quality and mood., Results: Women in the third trimester of pregnancy had poorer sleep efficiency, more awakenings, less stage 4 sleep, more stage 1 sleep and fewer minutes in rapid eye movement sleep when compared to the control group. Cortical arousals were seen more often during pregnancy, particularly in response to respiratory events and limb movements. Sleep during the first trimester was affected to a lesser extent, with more wake time after sleep onset and less stage 4 sleep when compared to the controls., Conclusions: Sleep during pregnancy is compromised by higher amounts of wake and cortical arousals leading to sleep fragmentation, with greater amounts of light sleep and less deep sleep. Mood state did not have an effect on sleep. Given the impact of sleep on well-being, this study increases our understanding of the characteristics of sleep during pregnancy, to help recognise when severe sleep disruption may warrant referral to a specialist for appropriate diagnosis and treatment., (© 2010 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2010 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Given the prevalence of mild traumatic brain injury (mTBI) and enduring subjective complaints known as postconcussion symptoms (PCS), it is important to investigate the nature and extent of these difficulties. This study used meta-analytic techniques to integrate the available information on the emotional symptoms associated with mTBI. Small effect sizes were found across all domains (depression, anxiety, coping, and psychosocial disability); however, significance depended upon the weighting method employed. The results indicate that mTBI had a small to negligible effect on emotional symptom reporting. This has implications for the etiology of PCS, the delivery of therapeutic interventions, and medico-legal disputations.

This series of experiments investigated the role of protein translation and RNA synthesis on consolidation and reconsolidation of passive avoidance learning (PAL) in day-old chicks. Although it is well established that protein translation is required after a reminder, there are conflicting reports in the literature concerning the requirement for RNA synthesis at this time. Day-old male New HampshirexWhite Leghorn chicks were trained on a single trial passive avoidance task. The results confirmed the requirement for protein translation during reconsolidation with memory deficits induced by anisomycin (ANI) (10mg/kg) detected at 60min post-reminder. It was also established that RNA synthesis was required for consolidation of PAL through inhibition by 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) (0.075microg/kg), administered at or after training. The same dose of DRB was also found to inhibit memory post-reactivation. However injections were required before the reminder trial and memory deficits were evident by 60min, consistent with that found for ANI post-reminder. As with ANI, the DRB-induced memory deficit post-reminder was also transient, and resolved by 24h post-reminder. For both reconsolidation drug studies, the memory deficit was wholly dependent on the memory being reactivated by a reminder-trial. The study highlights an important role for RNA synthesis following memory reactivation.

There is an increasing evidence that long-term alcohol intake can promote damage to most of the body's major organs. However, regular consumption of a small-moderate amount of alcohol is often recommended as being beneficial to health and of concern is that the effect of ingesting commercially available alcohol products on steroid hormone synthesis under variable nutritional conditions has not been thoroughly investigated. Many individuals consume alcohol alone prior to a meal and the aim of the present study was to assess the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary cortisol and salivary dehydroepiandrosterone sulfate (DHEAS) before and after a meal. A total of 24 males aged 19-22 years participated in the current investigation. The experimental procedure required participants to fast for 6 h before being asked to ingest either 40 g alcohol in the form of red wine (n=8), low alcohol and high beer (n=8), white wine (n=8) or the equivalent amount of placebo over a 135-min period before consuming food for 45-min. The level of blood alcohol, salivary cortisol and salivary DHEAS was assessed upon arrival and then at regular 45-min intervals during the 180-min experimental period. The results showed that the consumption of alcohol and placebo can significantly lower the level of salivary cortisol. However, the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary DHEAS was dependent on the nutritional content of the beverage with red wine promoting no change, white wine promoting a significant decrease, and beer having a variable effect on salivary DHEAS concentration when compared to placebo. It was concluded that the effect of commercially available alcohol on the HPA axis is not the same for all alcohol products and both the nutritional status of participants and the nutritional content of the alcoholic beverage being administered should be taken into consideration when investigating the effect of alcohol on the HPA axis.

This series of studies examined the effect of the PDE4 inhibitors rolipram and YM976 on the recall of the passive avoidance learning (PAL) task in the day old chick, with a particular focus on the role of D1 receptor in activating this pathway. The results indicated that 2.0 mg/kg rolipram administered 5 min before or immediately, 5, 15 or 30 min following training and 0.025 mg/kg YM976 administered 15 min before or immediately, 5, or 15 min following training facilitated recall of the weak form of the task (i.e. using 20% v/v methyl anthranilate (MeA) as the aversant) at 180 min following training. In each case the effect emerged from 60 min following the training, and was still observable from 180 min to 24 h after training. In addition, whilst administration of 0.5 mg/kg SCH23390, a D1 receptor antagonist, 10 min prior to training disrupted recall for the strong form of the task, co-administration of 2.0 mg/kg rolipram but not 0.025 mg/kg YM976 5 min prior to training prevented this disruption occurring. The results suggest a role for D1 receptor activation in the processes underlying the facilitation of memory by rolipram.

Introduction: This study investigated the effects of trait anxiety and state worry on working memory performance in a normal sample. Phase one investigated the effects of trait anxiety and state worry on the capacity of specific working memory components. Phase two investigated the validity of Eysenck and Calvo's (1992) Processing Efficiency Theory of worry., Method: Sixty adult participants (40 females and 20 males with a mean age of 26 years) were assigned to a 2 (trait anxiety: Low vs. high)x2 (state worry: Low vs. high) between-subjects design., Results: Contrary to prediction, worry did not lead to a decrement in performance on verbal working memory tasks but unexpectedly enhanced performance on visual tasks in participants with low trait anxiety (LTA). The results were also in opposition to expectations for Phase two. Individuals in the conditions of high trait anxiety and/or high state worry (LTA/HW, HTA/LW, and HTA/HW) displayed shorter response latencies than individuals in the LTA and low state worry (LTA/LW) condition on both verbal and spatial working memory (i.e., N-back) tasks., Conclusion: Although non-pathological worry is predominantly a verbal-linguistic activity, it may also be complemented by the processing of visual imagery which facilitates problem-solving and adaptive functions.

Gamma-butyrolactone (GBL) is a prodrug to gamma-hydroxybutyric acid (GHB) and metabolises to GHB when ingested. Discrimination stimulus studies report generalisation of effects of GHB to GBL. While amnesia is one of the most commonly reported symptoms of GHB's ingestion in human users, as yet few studies have examined this effect. Although an endogenous GHB specific receptor is present in the brain, several studies have indicated that the clinical effects of exogenous doses of GBL/GHB are due to its action on GABA(B) receptors rather than on the GHB receptor. In this series of studies, New Hampshire x White leghorn cockerels were trained using a modified version of the passive avoidance learning task. Subcutaneous injections of GBL induced a memory deficit by 10 min post-training, which persisted for at least 24 h. No effect on memory was seen with administration of the specific GHB agonist NCS-356 (gamma-p-chlorophenyl-trans-4-hydroxycrotonate). The GBL-induced memory deficit appeared similar to the deficit produced by baclofen, where the antagonist facilitated learning. Additionally, GBL-induced memory deficit was ameliorated by application of a GABA(B) antagonist. The results support the hypothesis that GBL exerts its influence on memory via the GABA(B) receptor rather than by the specific GHB receptor.

This paper reports two studies which investigated the effect of interference on delayed recall scores of the WMS-III and other commonly used memory measures. In Study 1, participants completed the immediate and delayed components of the WMS-III, with or without the introduction of conceptually similar memory tasks between the recall trials. In Study 2, this order of administration was reversed, with the WMS-III subtests used as the interference items. The results indicated that the introduction of interference items during the delay negatively affected delayed recall performance on almost all sub-tests. In addition, equal effects of proactive and retroactive interference were demonstrated. These findings raise concerns regarding the standardization process for memory tasks and highlight the need to consider interference effects in clinical practice, and stand as a caution in the use of memory-related materials during the delay interval in memory testing.

Cyclin-dependent kinase 5 (CDK-5) is reported to phosphorylate the NMDA receptor prior to the induction of long-term potentiation (LTP), among its many other effects. Application of CDK-5 inhibitors disrupts LTP and results in impaired task acquisition in behaving animals. In this study, we investigated the effect of exogenously applied roscovitine, a potent CDK-5 inhibitor, on consolidation and reconsolidation processes in day-old male chicks. New Hampshire x White leghorn cockerels were trained using a modified version of the passive avoidance learning task. Intracranial injections of roscovitine (2.5 microM) administered immediately after training induced a memory deficit that evolved from 5-minute post-training and persisted until at least 24 h following training. Injections of roscovitine (2.75 microM) administered immediately after the reminder trial induced a memory deficit observed by 30-minute post-reminder which had resolved by 24 h following the reminder. The comparison between consolidation and reconsolidation demonstrates differences both in the time of the onset of the memory deficit as well as in the permanence of this deficit. The results suggest an important, although different role for CDK-5 in consolidation and reconsolidation processes following passive avoidance learning.

Both NMDA and non-NMDA receptors participate in the consolidation of passive avoidance learning (PAL) in the day-old chick. NMDA antagonists have also been implicated in reconsolidation processes following reminder-trials. In this study, we examined the effect of administering 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, on reconsolidation following memory reactivation. New Hampshire x White leghorn cockerels were trained using a modified version of the PAL task. When CNQX was administered 20 min following a reminder trial, a retention deficit was detected at 90 min, but this had resolved by 24 h following the reminder. The parameters of the reconsolidation deficit were similar to those induced by CNQX injections post-training with the exception of their transience. This finding suggests that the action of non-NMDA receptors may perform a similar role in both consolidation and reconsolidation processes.

A one-trial learning task, where chicks learn that a bead of a particular shape and/or colour has a bitter taste (because it has been coated in 100% methyl anthranilate, MeA) and subsequently avoids it on test, has been widely used by research groups across the world. However, there are some differences in the results reported by different research laboratories. One important difference is found when chicks are trained with a diluted bitter taste on the bead (10 or 20% MeA); memory is not consolidated and fades, lasting for different times. At Monash and La Trobe Universities, memory lasts for 30 min but at the Open University (OU), memory lasts for 4-6h before fading. Differences in protocol that may explain this apparent discrepancy are whether the chicks have seen the bead before (novelty) and whether the colour or the shape of the bead is an important feature. In this review, we discuss these and other factors that may contribute to the differences in the characteristics of memory processing at Monash and at the OU, such as chick strain, hatchery or laboratory incubated chicks, age at training. It is clear that there is a difference between passive avoidance and discriminative avoidance protocols and this may explain the differences in duration of the memory with weakly reinforced learning. Is the OU task a more salient experience because of the novelty of the bead and therefore a 'stronger' learning experience? The different protocols may allow different questions to be addressed.

It has been one of the unshakeable orthodoxies of memory research that memory is initially laid down in a labile form for a short period following the experience and that over time the memory is "fixed" or "consolidated" into the physical structure of the brain. Over the last decade a large body of data has gathered which demonstrates that a "consolidated" memory can be returned to a labile state following retrieval of material from the store, which can then be re-consolidated, incorporating the newly acquired information into the representation of the world. The process of re-consolidation thus provides a sensible means for the crucial process of memory updating to occur. The paper focuses on pharmaco-behavioural experiments undertaken in our laboratories as well as in those of other groups which use the day-old chick as subject and the passive avoidance learning (PAL) task to examine the behavioural and metabolic parameters of re-consolidation. The data indicate that the consolidation and the re-consolidation processes are similar but not identical physiological processes. The re-processing of the memory following a re-consolidation involves each of the glutamatergic, adrenergic and dopaminergic neurotransmitter systems as well as re-activation of protein synthesis associated with the respective traces. In the chick model system, the ability to undertake re-consolidation is transient, and is observed only for a maximum of 24-48 h following the initial training event. Controversy persists as to whether the re-consolidated memory represents a new memory or whether it is a modification of the original memory processing.

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.

This study investigated the effect of ouabain, an inhibitor of NA(+) and K(+) ATPase, on consolidation and reconsolidation of a passive avoidance learning task in the day-old chick. In the consolidating trace, ouabain is thought to inhibit an intermediate-term memory phase, some aspects of which acts as a "trigger" for long-term stabilisation of the trace by new protein synthesis. It was hypothesised that a similar process may initiate the protein synthesis observed following reminder-activated reconsolidation in the young chick. Chicks were trained on a single trial passive avoidance task. A dose of 0.2 ug/kg ouabain was administered intracranially either 5 min post-training (consolidation processes) or 5 min post-reminder (reconsolidation processes). Consistent with previous research, ouabain administration induced a memory deficit following the initial learning trial. However, contrary to expectation, ouabain did not disrupt memory processing post-reactivation. This finding provides further evidence for the notion that consolidation and reconsolidation are associated with similar, but distinct, stages of processing.

Primary Objective: To investigate the relationship of working memory, processing speed and verbal comprehension with FAS performance in individuals who had sustained a traumatic brain injury (TBI)., Methods and Procedure: Sixty-three patients with a TBI were grouped according to the presence of impaired verbal fluency performance and then compared on a number of cognitive and demographic variables., Results: Following a TBI, working memory and processing speed had the greatest influence on verbal fluency performance. For those individuals who have not sustained a TBI, education, verbal intelligence, working memory and speed of information processing were related to FAS performance., Conclusions: The findings of the study indicate that FAS performance was related to verbal intelligence, working memory ability, attention and speed of information processing. The results further suggest that different variables are related to FAS performance following a TBI as compared with control group performances.

Anecdotal and experimental evidence has demonstrated that humans and animals exhibit physiological and cognitive alterations in response to sickness and injury. It is now clear that these changes are due to the actions of proinflammatory cytokines. The current study examined the effects of peripheral administration of polyinosinic:polycytidylic acid, a synthetic double-stranded viral RNA, on the memory processes of day-old chicks trained on a single trial passive avoidance task. Polyinosinic:polycytidylic acid impaired performance on the passive avoidance task in a dose-dependent manner. Maximal deficits were observed when 5 g/kg polyinosinic:polycytidylic acid was administered 120 min before training. Tests for retention revealed that interference in memory consolidation appeared between 30 and 40 min after training. These results indicate an inhibitory effect of polyinosinic:polycytidylic acid on the processes of memory formation at the transition from intermediate-term memory phase (A) to intermediate-term memory phase (B) of the Gibbs and Ng model of memory formation. The study also investigated the pyrogenic actions of polyinosinic:polycytidylic acid, and examined the effect of pretreatment with ketoprofen, a cyclooxygenase inhibitor. Significant rises in body temperature were observed 30 min after injection of polyinosinic:polycytidylic acid. Inhibition of cyclooxygenase by ketoprofen ameliorated the polyinosinic:polycytidylic acid-induced deficits in retention and attenuated the increase in body temperature. These results demonstrate that polyinosinic:polycytidylic acid induces memory processing deficits and is pyrogenic in the day-old chick and that these effects are cyclooxygenase-dependent.

Primary Objective: To investigate the relationship between naming difficulty (ND) and FAS performance in traumatic brain injury (TBI)., Methods and Procedure: Sixty-three patients with a TBI were divided into two groups based on the presence of a ND and were compared with a control group on FAS performance., Results: Whilst the group with a TBI performed more poorly than the control group on the FAS task, there was no difference between those participants who featured a ND and those who did not. The TBIs produced fewer words than the control group in the first time slice of the task, but there was no difference between the group with a ND and the non-ND group on this measure., Conclusion: The results indicate that the effect of word finding deficits is not the principal cause of the diminution of phonemic verbal fluency performance in TBI, which is probably more likely due to compromise in speed of information processing associated with the injury.

Background/aims: The present study aims to investigate the contribution of alcohol toxicity to the development of malnutrition by assessing the effect of consuming a moderate amount of white wine on plasma insulin and serum IgA under fasting conditions., Methods: A total of 5 non-alcoholic males aged between 19 and 22 years participated in the current investigation. The experimental procedure required participants to undergo a 6-hour fast before ingesting 4 standard units of alcohol (40 g) in the form of white wine over a 120-min period. The level of blood alcohol, plasma insulin and serum IgA was assessed at 30-min intervals across the 120-min experimental period., Results: Consuming alcohol promotes a significant increase in serum IgA in the absence of any change in plasma insulin or ketone production in fasted individuals., Conclusion: White wine prior to a meal does not promote glucose metabolism and utilization and may increase the risk of developing a transient diabetic condition due to an alteration in energy metabolism., (Copyright (c) 2006 S. Karger AG, Basel.)

Twenty participants with self-reported long-term benzodiazepine use (mean 108 months) who had previously withdrawn from medication (mean 42 months) were administered a battery of neuropsychological tests. Each long-term user was case matched for age, sex, and education to two control participants who reported never taking benzodiazepines (those with and those without anxiety). The results indicated that long-term benzodiazepine use may lead to impairments in the areas of verbal memory, motor control/performance, and nonverbal memory but not visuospatial skills and attention/concentration. The length of abstinence (> 6 months) indicates that these impairments persist well beyond cessation of benzodiazepine use. However, observed impairments in the area of nonverbal memory were not solely attributable to benzodiazepine use and may be influenced by the elevated anxiety levels present in both the case and the anxious control group.

This series of experiments examined the involvement of the dopamine D1 receptor antagonist, SCH23390, on memory reconsolidation following reminder-activated retrieval. Day-old male New HampshirexWhite Leghorn chicks were trained on a single trial passive avoidance task. A dose of 0.5 mg/kg of SCH23390 was administered subcutaneously 5 min before reminder trials, which were presented at 30, 60, and 90 min following training. Memory deficits were observed when reminder trials were presented at 30 and 60 min following training, but not when a reminder was presented at 90 min. No effect on memory retention was observed when reminder trials were not presented, suggesting that reconsolidation mechanisms were both contingent on the presentation of the reminder and independent of the consolidation process. Following a reminder presented at 60 min post-training, deficits in memory retention emerged between 45 and 60 min. The deficit was prolonged, lasting for up until 48 h after reminder presentation. The results indicate an important role for the D1 receptor in reconsolidation processes.

The purpose of the current study was to explore whether performance on standardised neuropsychological measures could predict functional ability with automated machines and services among people with an acquired brain injury (ABI). Participants were 45 individuals who met the criteria for mild, moderate or severe ABI and 15 control participants matched on demographic variables including age- and education. Each participant was required to complete a battery of neuropsychological tests, as well as performing three automated service delivery tasks: a transport automated ticketing machine, an automated teller machine (ATM) and an automated telephone service. The results showed consistently high relationship between the neuropsychological measures, both as single predictors and in combination, and level of competency with the automated machines. Automated machines are part of a relatively new phenomena in service delivery and offer an ecologically valid functional measure of performance that represents a true indication of functional disability.

This series of studies used a weakly trained (20% methyl anthranilate) version of the passive avoidance learning task in the 1-day-old chick to investigate memory facilitation effects by diphenylhydantoin (DPH). The results indicated that the pairing of the weak training experience with DPH results in facilitation of memory that can be observed from 40 min following training with the weak training experience. The results from a biochemical experiment indicated that DPH facilitates the activity of Na(+)/K(+)-ATPase at the majority of times sampled in a large percentage of the sections of the chick brain. The most marked level of elevation in the activity of the enzyme was observed at the 20-min time point following weak training in the section of the chick brain, which contained several memory relevant neuroanatomical loci. This represents a 68% increase in the activity of the enzyme in those areas considered to be crucial to the processing of memory in the paradigm at a time predicted by previous investigation to be crucial in the development of the intermediate-term memory stage of memory. The results of this series of studies support the notion that Na(+)/K(+)-ATPase plays an important role in memory processing following passive avoidance training in the 1-day-old chick.

Despite the widespread prescribing of benzodiazepines, uncertainty still surrounds the potential for cognitive impairment following their long-term use. Furthermore, the degree of recovery that may take place after withdrawal or the level of residual impairment, if any, that is maintained in long-term benzodiazepine users is also unclear. The current paper employed meta-analytic techniques to address two questions: (1) Does the cognitive function of long-term benzodiazepine users improve following withdrawal? (2) Are previous long-term benzodiazepine users still impaired at follow-up compared to controls or normative data? Results of the meta-analyses indicated that long-term benzodiazepine users do show recovery of function in many areas after withdrawal. However, there remains a significant impairment in most areas of cognition in comparison to controls or normative data. The findings of this study highlight the problems associated with long-term benzodiazepine therapy and suggest that previous benzodiazepine users would be likely to experience the benefit of improved cognitive functioning after withdrawal. However, the reviewed data did not support full restitution of function, at least in the first 6 months following cessation and suggest that there may be some permanent deficits or deficits that take longer than 6 months to completely recover.

Introduction: While benzodiazepines are the most widely used psychotropic drugs, there are relatively few studies that have examined deficits in cognitive functioning after long-term use. The literature that is available is difficult to interpret due to conflicting results as well as a variety of methodological flaws., Objective: To systematically evaluate and integrate the available research findings to determine the effect of long-term benzodiazepine use on cognitive functioning using meta-analytical techniques., Methods: Thirteen research studies that employed neuropsychological tests to evaluate cognitive performance after long-term use of benzodiazepine medication met inclusion criteria. The neuropsychological tests employed in these 13 studies were each categorised as measuring one of 12 cognitive domains. Separate effect sizes were calculated for each of the 12 cognitive categories. Each study was only allowed to contribute one effect size to each cognitive category by averaging together the effect sizes from the same study if more than one type of test was used to measure a particular category. This strategy resulted in equal weight being given to each study per category, regardless of the number of tests in that category., Results: The overall mean number of patients who were benzodiazepine users was 33.5 (SD +/- 28.9) and the mean number of controls was 27.9 (SD +/- 19.6). The duration of benzodiazepine use ranged from 1 to 34 (mean 9.9) years. Long-term benzodiazepine users were consistently more impaired than controls across all cognitive categories examined, with effect sizes ranging in magnitude from -1.30 to -0.42. The mean weighted effect size was -0.74 (SD +/- 0.25). None of the effect sizes had 95% CIs that spanned zero and, therefore, all of these effects were significant and different to zero., Conclusion: Moderate-to-large weighted effect sizes were found for all cognitive domains suggesting that long-term benzodiazepine users were significantly impaired, compared with controls, in all of the areas that were assessed. However, this study has several limitations, one being that it includes a relatively small number of studies. Further studies need to be conducted; ideally, well designed, controlled studies that thoroughly investigate certain areas of cognitive functioning and present data in such a way so as to be amenable to inclusion in a meta-analysis. Incorporating the information from these studies into a larger meta-analysis would allow for a more thorough and statistically sound investigation of the effects of moderator variables. The observation that long-term benzodiazepine use leads to a generalised effect on cognition has numerous implications for the informed and responsible prescription of these drugs.