Working memory performance and cognitive flexibility after dexamethasone or hydrocortisone administration in healthy volunteers

Objective

Several studies have shown that glucocorticoids can impair declarative memory retrieval and working memory (WM) performance. The aim of the present study was to investigate the impact of a high dose of hydrocortisone on WM, as well as to examine the effects of cortisol suppression via treatment with a high dose of dexamethasone (DEX). We hypothesized that hydrocortisone treatment results in an impaired cognitive function compared with placebo. We further expected that dexamethasone treatment is also followed by cognitive impairment, due to the hypothesis that very low levels of cortisol are also associated with alterations in memory performance.

Methods

In a placebo-controlled study with a within-subject design, 16 healthy volunteers received placebo or 120?mg of hydrocortisone (two boluses of 60?mg) directly before neuropsychological testing or 4?mg of DEX the day before testing.

Results

We did not find any effect of hydrocortisone on WM and cognitive flexibility, even though cortisol levels were high at the time of testing. Furthermore, we did not find any effect of DEX treatment on WM and reaction time in a cognitive flexibility test. However, cognitive flexibility was negatively correlated with adrenocorticotropin (ACTH) in the DEX condition.

Conclusions

Our results found no clear effect of hydrocortisone and dexamethasone treatment on WM. These results emphasize the need for further research on the association between hypothalamic?Cpituitary?Cadrenal axis activity and cognition. These studies should investigate the hypotheses of dose-dependent associations in more detail and should also include analyses on ACTH and cognition.     

Methylphenidate produces selective enhancement of declarative memory consolidation in healthy volunteers

Rationale

Methylphenidate inhibits the reuptake of dopamine and noradrenaline and is used to treat children with attention deficit hyperactivity disorder (ADHD). Besides reducing behavioral symptoms, it improves their cognitive function. There are also observations of methylphenidate-induced cognition enhancement in healthy adults, although studies in this area are relatively sparse. We assessed the possible memory-enhancing properties of methylphenidate.

Objective

In the current study, the possible enhancing effects of three doses of methylphenidate on declarative and working memory, attention, response inhibition and planning were investigated in healthy volunteers.

Methods

In a double blind placebo-controlled crossover study, 19 healthy young male volunteers were tested after a single dose of placebo or 10, 20 or 40?mg of methylphenidate. Cognitive performance testing included a word learning test as a measure of declarative memory, a spatial working memory test, a set-shifting test, a stop signal test and a computerized version of the Tower of London planning test.

Results

Declarative memory consolidation was significantly improved relative to placebo after 20 and 40?mg of methylphenidate. Methylphenidate also improved set shifting and stopped signal task performance but did not affect spatial working memory or planning.

Conclusions

To the best of our knowledge, this is the first study reporting enhanced declarative memory consolidation after methylphenidate in a dose-related fashion over a dose range that is presumed to reflect a wide range of dopamine reuptake inhibition.     

Effects of hydrocortisone administration on cognitive function in the elderly

Previous studies have found adverse effects of both acute and chronic elevations of corticosteroids on cognitive function in humans and that cortisol levels may predict cognitive decline in elderly subjects. However, no previous studies have directly investigated the effects of hydrocortisone on cognitive functioning in the healthy elderly. Sixteen healthy elderly subjects took part in a placebo-controlled, double-blind, cross-over trial. Hydrocortisone 20 mg or placebo was administered twice, 12 h and 1 h before cognitive testing. On each occasion, a battery of neuropsychological tests was performed which included tests of attention, working memory, declarative memory and executive function. Salivary cortisol levels at the time of testing were elevated approximately 10-fold following hydrocortisone compared with placebo. No significant effects were found on memory or a range of other cognitive functions. The lack of effect of this regime of hydrocortisone is in contrast to studies in younger subjects. The elderly may be less sensitive to cognitive effects of short-term increases in cortisol levels, possibly due to an age-related downregulation of hippocampal glucocorticoid receptors.     

DRD2 genotype predicts prefrontal activity during working memory after stimulation of D2 receptors with bromocriptine

Rationale

Pharmacological stimulation of D2 receptors modulates prefrontal neural activity associated with working memory (WM) processing. The T allele of a functional single-nucleotide polymorphism (SNP) within DRD2 (rs1076560 G > T) predicts reduced relative expression of the D2S receptor isoform and less efficient neural cortical responses during WM tasks.

Objective

We used functional MRI to test the hypothesis that DRD2 rs1076560 genotype interacts with pharmacological stimulation of D2 receptors with bromocriptine on prefrontal responses during different loads of a spatial WM task (N-Back).

Methods

Fifty-three healthy subjects (38 GG and 15 GT) underwent two 3-T functional MRI scans while performing the 1-, 2- and 3-Back versions of the N-Back WM task. Before the imaging sessions, either bromocriptine or placebo was administered to all subjects in a counterbalanced order. A factorial repeated-measures ANOVA within SPM8 (p?<?0.05, family-wise error corrected) was used.

Results

On bromocriptine, GG subjects had reduced prefrontal activity at 3-Back together with a significant decrement in performance, compared with placebo. On the other hand, GT subjects had lower activity for the same level of performance at 1-Back but a trend for reduced behavioral performance in the face of unchanged activity at 2-Back.

Conclusions

These results indicate that bromocriptine stimulation modulates prefrontal activity in terms of disengagement or of efficiency depending on DRD2 genotype and working memory load.     

Enhanced effects of cortisol administration on episodic and working memory in aging veterans with PTSD.

Though both glucocorticoid alterations and memory impairments have been noted in posttraumatic stress disorder (PTSD), it is not clear if these phenomena are causally linked. As there is emerging evidence that these domains become further altered in PTSD with increasing age, it is of interest to examine these relationships in an older cohort. Aging (mean age, 62.7+/-8.9; range, 52-81) combat veterans with (n=13) and without (n=17) PTSD received an intravenous bolus of 17.5 mg hydrocortisone (cortisol), a naturally occurring glucocorticoid, or placebo in a randomized, double-blind manner, on two mornings approximately 1-2 weeks apart. Neuropsychological testing to evaluate episodic and working memory performance was performed 75 min later. Cortisol enhanced episodic memory performance in both groups of subjects, but enhanced elements of working memory performance only in the PTSD+ group. The preferential effect of cortisol administration on working memory in PTSD may be related to the superimposition of PTSD and age, as cortisol had impairing effects on this task in a previously studied, younger cohort. The findings suggest that there may be opportunities for developing therapeutic strategies using glucocorticoids in the treatment of aging combat veterans.     

Amphetamine effects on MATRICS Consensus Cognitive Battery performance in healthy adults

Background

Cognitive deficits contribute strongly to functional disability in schizophrenia. The cost of identifying and testing candidate procognitive agents is substantial. Conceivably, candidate drugs might be first identified by positive effects on cognitive domains in sensitive subgroups of healthy subjects. Here, we examined whether the MATRICS Consensus Cognitive Battery (MCCB) detected procognitive drug effects in subgroups of healthy individuals.

Methods

The effects of 20 mg amphetamine (AMPH) on MCCB performance were tested in a double-blind, placebo-controlled crossover study of 60 healthy adults. AMPH effects were compared in subgroups of subjects characterized by low vs. high placebo MCCB scores, and by extreme values on personality subscales associated with schizophrenia-relevant biomarkers.

Results

AMPH produced autonomic and subjective effects, but did not significantly change MCCB composite scores or individual domain scores across the inclusive sample of 60 subjects. AMPH-induced MCCB changes were significantly (inversely) related to placebo MCCB performance: among individuals with lower placebo scores, AMPH enhanced performance; while among individuals with higher placebo scores, it impaired performance. A potential impact of regression to the mean was assessed and could not be ruled out. Both placebo MCCB performance and AMPH effects on MCCB scores were significantly related to personality domains associated with schizophrenia-linked genetic- and/or neurophysiological substrates.

Conclusions

Among healthy adults, AMPH effects on MCCB performance were detected only among specific subgroups, and in specific cognitive domains. Strategies that utilize drug-induced changes in MCCB performance in healthy subjects to screen for candidate procognitive drugs should consider the use of “enriched” subgroups with specific neurocognitive or personality characteristics.     

Residual effects of zopiclone 7.5 mg on highway driving performance in insomnia patients and healthy controls: a placebo controlled crossover study

Rationale

Residual effects of hypnotics on driving performance have been mainly determined in studies using a standardized driving test with healthy good sleepers. Responses to effects may differ, however, between insomniacs and healthy volunteers due to the underlying sleep disorder. In addition, a majority of insomniacs uses hypnotics chronically resulting in the development of tolerance to impairing effects. Impaired driving performance in healthy volunteers may then be an overestimation of the actual effects in insomniacs.

Objectives

The present study aims to compare the residual effects of zopiclone 7.5 mg on on-the-road driving performance of 16 middle-aged insomniacs chronically using hypnotics (chronic users), 16 middle-aged insomniacs not or infrequently using hypnotics (infrequent users), and 16 healthy, age matched, good sleepers (controls).

Methods

The study was conducted according to a 3?×?2 double-blind, placebo controlled crossover design, with three groups and two treatment conditions. Treatments were single oral doses of zopiclone 7.5 mg and placebo administered at bedtime (2330 hours). Between 10 and 11 h after administration subjects performed a standardized highway driving test.

Results

Zopiclone 7.5 mg significantly impaired on-the-road driving performance in both insomnia groups and healthy controls. The magnitude of impairment was significantly less in the chronic users group as compared with the controls.

Conclusions

The smaller magnitude of effects suggests that investigating residual effects of hypnotics in healthy volunteers may yield a minor overestimation of the actual effects in insomnia patients.     

The effects of energy drink in combination with alcohol on performance and subjective awareness

Rationale

This study investigated the coadministration of an energy drink with alcohol to study the effects on subjective intoxication and objective performance.

Objectives

This study aims to evaluate the objective and subjective effects of alcohol versus placebo at two alcohol doses, alone and in combination with an energy drink, in a balanced order, placebo-controlled, double-blind design.

Methods

Two groups of ten healthy volunteers, mean (SD) age of 24 (6.5), participated in the study. One group consumed energy drink containing 80?mg of caffeine and the other consumed a placebo drink, with both receiving two alcohol doses (0.046 and 0.087% breathalyser alcohol concentration). Tests included breath alcohol assessment, objective measures of performance (reaction time, word memory and Stroop task) and subjective visual analogue mood scales.

Results

Participants showed significantly impaired reaction time and memory after alcohol compared to the no alcohol condition and had poorer memory after the higher alcohol dose. Stroop performance was improved with the energy drink plus alcohol combination compared to the placebo drink plus alcohol combination. Participants felt significant subjective dose-related impairment after alcohol compared to no alcohol. Neither breath alcohol concentration nor the subjective measures showed a significant difference between the energy drink and the placebo energy drink when combined with alcohol.

Conclusions

Subjective effects reflected awareness of alcohol intoxication and sensitivity to increasing alcohol dose. There were no overall significant group differences for subjective measures between energy drink and placebo groups in the presence of alcohol and no evidence that the energy drink masked the subjective effects of alcohol at either dose.     

Drinking and future thinking: acute effects of alcohol on prospective memory and future simulation

Background

It has recently been shown that acute alcohol globally impairs ‘prospective memory’ (PM)—remembering to do something in the future (Leitz et al. in Psychopharmacology 205:379–387, 2009). In healthy, sober individuals, simulating future events at encoding enhances PM performance.

Aims

We therefore aimed to determine if future event simulation could attenuate the impairing effects of acute alcohol on PM.

Methods

Using a double-blind independent group design, 32 healthy volunteers were administered a 0.6-g/kg dose of ethanol or matched placebo. PM performance was assessed using a behavioural task, the ‘Virtual Week’, which was adapted to enable future event simulation in both remote and recent contexts. Episodic memory was indexed with a source memory task and planning with the Tower of London task.

Results

We replicated the finding of Leitz et al. that acute alcohol consumption impairs prospective memory for event-based tasks. Future event simulation significantly improved PM performance on these tasks and eliminated the PM deficit caused by acute alcohol consumption.

Conclusions

This is the first evidence that future event simulation can overcome alcohol-induced deficits in prospective memory and may have important clinical implications for the rehabilitation of chronic alcohol users.     

Glucose administration prior to a divided attention task improves tracking performance but not word recognition: evidence against differential memory enhancement?

Rationale

The cognition-enhancing effects of glucose administration to humans have been well-documented; however, it remains unclear whether this effect preferentially targets episodic memory or other cognitive domains.

Objectives

The effect of glucose on the allocation of attentional resources during memory encoding was assessed using a sensitive dual-attention paradigm.

Materials and methods

One hundred and twenty volunteers (mean age 21.60, SD 4.89, 77 females) took part in this randomised, double-blind, placebo-controlled, parallel groups study where each consumed a 25-g glucose drink or a placebo. Half of the participants in each drink condition attempted to track a moving on-screen target during auditory word presentation. The distance between the cursor and the tracking target was used as an index of attentional cost during encoding. Effects of drink and tracking on recognition memory and drink on tracking performance were assessed. Self-rated appetite and mood were co-monitored.

Results

Co-performing the tracking task significantly impaired memory performance irrespective of drink condition. In the placebo–tracking condition, there was a cost to tracking manifest as greater deviation from target during and immediately following word presentation. Compared with placebo, the glucose drink significantly improved tracking performance during encoding. There were significant time-related changes in thirst and alertness ratings but these were not differentially affected by drink or tracking conditions.

Conclusion

Tracking but not memory was enhanced by glucose. This finding suggests that, under certain task conditions, glucose administrations does not preferentially enhance memory performance. One mechanism through which glucose acts as a cognition enhancer is through allowing greater allocation of attentional resources.     

A placebo-controlled study of sildenafil effects on cognition in schizophrenia

Background

Phosphodiesterase 5 (PDE5) inhibitors increase cyclic guanosine monophosphate (cGMP) concentrations in the intracellular pathway activated by N-methyl-d-aspartic acid receptors which is believed to mediate long-term potentiation and memory consolidation. The PDE5 inhibitor sildenafil has been shown to enhance memory in animal models. In addition, neuronal nitric oxide synthase, another component of the NMDA/nitric oxide/cGMP intracellular pathway, has been reported to be dysregulated in schizophrenia patients.

Materials and methods

Seventeen adult schizophrenia outpatients treated with a stable dose of antipsychotic received a single oral dose of placebo, sildenafil 50 mg, and sildenafil 100 mg in random order with a 48-h interval between administrations. Psychiatric symptom ratings and a cognitive battery were performed at baseline and 1 hour following each administration of the study drug. In addition, memory consolidation was examined by testing recall 48 h later, prior to the next administration of the study drug.

Results

Fifteen subjects completed all three treatment conditions. One subject developed irritability and required hospitalization 2 days after receiving sildenafil 100 mg. Neither dose of sildenafil significantly affected cognitive performance or symptom ratings compared to the placebo.

Conclusion

Despite evidence for cognitive-enhancing effects of sildenafil in animal models, the strategy for treating putative NMDA receptor-mediated memory deficits in schizophrenia with sildenafil 50 and 100 mg was not successful. It is possible that the doses used in this study were not optimal or that repeated dosing may be necessary to achieve therapeutic effects. Agents under development that inhibit other subtypes of PDE remain promising for schizophrenia and dementia.     

Acute effects of ayahuasca on neuropsychological performance: differences in executive function between experienced and occasional users

Background

Ayahuasca, a South American psychotropic plant tea containing the psychedelic 5-HT_2A receptor agonist N,N-dimethyltryptamine, has been shown to increase regional cerebral blood flow in prefrontal brain regions after acute administration to humans. Despite interactions at this level, neuropsychological studies have not found cognitive deficits in abstinent long-term users.

Objectives

Here, we wished to investigate the effects of acute ayahuasca intake on neuropsychological performance, specifically on working memory and executive function.

Methods

Twenty-four ayahuasca users (11 long-term experienced users and 13 occasional users) were assessed in their habitual setting using the Stroop, Sternberg, and Tower of London tasks prior to and following ayahuasca intake.

Results

Errors in the Sternberg task increased, whereas reaction times in the Stroop task decreased and accuracy was maintained for the whole sample following ayahuasca intake. Interestingly, results in the Tower of London showed significantly increased execution and resolution times and number of movements for the occasional but not the experienced users. Additionally, a correlation analysis including all subjects showed that impaired performance in the Tower of London was inversely correlated with lifetime ayahuasca use.

Conclusions

Acute ayahuasca administration impaired working memory but decreased stimulus–response interference. Interestingly, detrimental effects on higher cognition were only observed in the less experienced group. Rather than leading to increased impairment, greater prior exposure to ayahuasca was associated with reduced incapacitation. Compensatory or neuromodulatory effects associated with long-term ayahuasca intake could underlie preserved executive function in experienced users.     

Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats

Rationale

Several studies have documented impairments in memory processes as a result of ketamine administration; however, few studies have compared the profile of cognitive effects of ketamine to other drugs.

Objectives

The aim of this study was to compare the cognitive effects of ketamine with those of triazolam in healthy volunteers.

Methods

Doses of ketamine (0.2, 0.4 mg/kg intramuscular (i.m.)), triazolam (0.2, 0.4 mg/70 kg p.o.), and double-dummy placebos were administered to 20 volunteers under repeated measures, counterbalanced, double-blind conditions. Peak physiological, psychomotor, subjective, and cognitive effects were examined.

Results

Ketamine impaired balance when balance was assessed early in the task order, whereas triazolam impaired psychomotor coordination and divided attention irrespective of task order. Triazolam also tended to produce greater effects on working memory and episodic memory tasks than ketamine at doses that produced lower subjective effects and higher estimates of performance.

Conclusions

Ketamine produces less cognitive impairment than triazolam at doses that produced greater subjective effects. Thus ketamine does not produce the underestimation of cognitive impairment typically seen with triazolam.     

Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis

Background

Converging evidence indicates that prenatal exposure to immune challenge can induce long-term cognitive deficits relevant to schizophrenia. Such cognitive impairments may be related to deficient hippocampal neurogenesis at adult age.

Objectives

In the present study, we sought evidence for the possibility that chronic treatment with the reference atypical antipsychotic drug clozapine may improve prenatal infection-induced cognitive dysfunctions by stimulating adult hippocampal neurogenesis.

Methods

This hypothesis was tested in a well-established mouse model of prenatal immune challenge which is based on prenatal administration of the viral mimic, polyriboinosinic–polyribocytidilic acid (PolyI:C).

Results

We found that maternal PolyI:C (5 mg/kg, i.v.) exposure on gestation day 17 led to significant spatial working memory impairment and reduced hippocampal neurogenesis in the resulting offspring at adult age. The latter effect was apparent in postmortem immunohistochemical analyses of the cell proliferation marker bromodeoxyuridine and the microtubule-associated protein doublecortin, a marker of newborn neuronal cells. Chronic (3 weeks) administration of clozapine (5 mg/kg/day, i.p.) significantly improved the prenatal PolyI:C-induced working memory deficits, while at the same time, it negatively affected working memory performance in adult offspring born to control mothers. These bidirectional cognitive effects of clozapine were not paralleled by concomitant effects on adult hippocampal neurogenesis.

Conclusions

Our findings do not support the hypothesis that the atypical antipsychotic drug clozapine may influence cognitive functions by acting on adult neurogenesis in the hippocampus, regardless of whether the drug is administered to subjects with or without a neurodevelopmental predisposition to adult neuropathology.     

Green tea extract enhances parieto-frontal connectivity during working memory processing

Rationale

It has been proposed that green tea extract may have a beneficial impact on cognitive functioning, suggesting promising clinical implications. However, the neural mechanisms underlying this putative cognitive enhancing effect of green tea extract still remain unknown.

Objectives

This study investigates whether the intake of green tea extract modulates effective brain connectivity during working memory processing and whether connectivity parameters are related to task performance.

Material and methods

Using a double-blind, counterbalanced, within-subject design, 12 healthy volunteers received a milk whey-based soft drink containing 27.5 g of green tea extract or a milk whey-based soft drink without green tea as control substance while undergoing functional magnetic resonance imaging. Working memory effect on effective connectivity between frontal and parietal brain regions was evaluated using dynamic causal modeling.

Results

Green tea extract increased the working memory induced modulation of connectivity from the right superior parietal lobule to the middle frontal gyrus. Notably, the magnitude of green tea induced increase in parieto-frontal connectivity positively correlated with improvement in task performance.

Conclusions

Our findings provide first evidence for the putative beneficial effect of green tea on cognitive functioning, in particular, on working memory processing at the neural system level by suggesting changes in short-term plasticity of parieto-frontal brain connections. Modeling effective connectivity among frontal and parietal brain regions during working memory processing might help to assess the efficacy of green tea for the treatment of cognitive impairments in psychiatric disorders such as dementia.     

Effects of the adenosine A2A antagonist istradefylline on cognitive performance in rats with a 6-OHDA lesion in prefrontal cortex

Rationale

Altered cognitive function is a common feature of both the early and later stages of Parkinson’s disease (PD) that involves alterations in cortical dopamine content. Adenosine A_2A antagonists, such as istradefylline, improve motor function in PD, but their effect on cognitive impairment has not been determined.

Objective

The present study investigated whether impairment of working memory due to the loss of dopaminergic input into the prefrontal cortex (PFC) is reversed by administration of istradefylline. We also evaluated whether A_2A antagonist administration modulates dopamine levels in the PFC.

Methods

Bilateral lesions of the dopaminergic input to the PFC were produced in rats using 6-hydroxydopamine (6-OHDA). Cognitive performance was evaluated using an object recognition task and delayed alternation task. The effects of istradefylline, donepezil and methamphetamine on cognitive performance were examined. In addition, the effect of istradefylline on extracellular dopamine levels in the PFC was studied.

Results

PFC dopamine levels and cognitive performance were significantly reduced by 6-OHDA lesioning. Istradefylline, donepezil and methamphetamine improved cognitive performance of PFC-lesioned rats. Istradefylline increased dopamine levels in the PFC in both normal and PFC-lesioned rats.

Conclusions

PFC dopaminergic input plays an important role in working memory performance. Blockade of A_2A receptors using istradefylline reverses the changes in cognitive function, and this may be due to an increase in PFC dopamine content. Adenosine A_2A receptor antagonists not only improve motor performance in PD but may also lead to improved cognition.     

Exogenous cortisol acutely influences motivated decision making in healthy young men

Background

The glucocorticoid (GC) hormone cortisol is the end product of the hypothalamic–pituitary–adrenal axis (HPA axis). Acute psychological stress increases HPA activity and GC release. In humans, chronic disturbances in HPA activity have been observed in affective disorders and in addictive behaviour. Recent research indicates that acute effects of GCs may be anxiolytic and increase reward sensitivity. Furthermore, cortisol acutely influences early cognitive processing of emotional stimuli.

Methods

In order to extend such findings to more complex emotional-cognitive behaviour, the present study tested acute effects of 40 mg cortisol on motivated decision making in 30 healthy young men.

Results

Results showed that cortisol indeed increased risky decision making, as predicted. This effect occurred for decisions where making a risky choice could potentially yield a big reward. These results are discussed with respect to currently proposed mechanisms for cortisol’s potential anxiolytic effect and GCs’ involvement in reward systems.     

Cognitive effects of psychotomimetic drugs in rats discriminating number cues

Rationale

Deficits in memory and attention are broadly acknowledged during psychosis; however, experiments on modeled psychosis often test working memory without systematic manipulation of attentional demands.

Objectives

The major research goal was discovering which neurobehavioral processes, attention, or memory contributed more to drug-provoked performance deficits.

Materials and methods

Rats were trained to perform operant ratio discrimination (RD) tasks wherein the number of presses at a rear-wall lever was discriminated using one of two front-wall levers. Effects from four psychotomimetic drugs, the serotonin agonist 2,5-dimethoxy-4-iodoamphetamine, the noncompetitive NMDA-glutamate receptor antagonist phencyclidine (PCP), and two CB1-selective cannabinoid agonists, WIN 55,512-2 and AM 411, were assessed using a signal detection analytical overlay to dissociate cognitive from noncognitive motor and motivational disruptions. Further methods allowed dissociation of attention compromises from mnemonic deficits.

Results

For each test compound, at least one dose elicited decreased RD accuracy without affecting response rates, and task difficulty was shown to be a crucial dictator of accuracy effect specificities. Effects from both PCP and WIN 55,512-2 biased animals to select the response lever conditioned for denser reinforcement. The same two drugs rendered peculiar response patterns in distracter light session components, considering light blinks were included to divert subjects’ attention away from task-relevant information. The response patterns determined during distracter components of PCP/WIN testing sessions, counterintuitively, suggest performance enhancement.

Conclusion

Comprehensive viewing of RD performance patterns after drug administration indicates that sustained attention and transient information management are significantly impaired during the drug-induced psychosis state, while selective attention is less affected.     

Brahmi for the better? New findings challenging cognition and anti-anxiety effects of Brahmi (Bacopa monniera) in healthy adults

Rationale

A number of studies have indicated positive effects of long-term administration (3 months) of Bacopa monniera (Brahmi) on various cognitive functions especially memory and anxiety. However, inconsistent results in literature may be linked to various methodological issues.

Objective

The present study aimed to test the chronic effects (12 weeks) of 450 mg of a B. monniera (Brahmi) extract on learning and memory, information processing and anxiety in healthy adult Indian population.

Methods

The study design was a randomised, double-blind, placebo-controlled parallel design. Participants comprised of 72 healthy urban adults, both men and women, in the age range of 35–60 years who were educated and English speaking with basic knowledge of computers from Bangalore. The outcome measures included verbal learning and memory, inspection time, attention and interference. State and trait anxiety were additional outcome variables.

Results

In the present study, there were no significant differences between the two groups on any of the cognitive measures. However, there was a trend for lower state anxiety in the B. monniera (Brahmi) group as compared to placebo group.

Conclusions

The current study attempted to determine the chronic effects of single daily dose of 450 mg of Brahmi extract on cognitive performance and anxiety in healthy adults. The results of the current study are not in agreement with findings of some of the earlier studies which have found improvement both on cognitive parameters and a reduction of anxiety scores.     

Memantine, an NMDA receptor antagonist, differentially influences Go/No-Go performance and fMRI activity in individuals with and without a family history of alcoholism

Rationale

Individuals with a family history of alcoholism (family history positive [FHP]) show higher alcoholism rates and are more impulsive than those without such a family history (family history negative [FHN]), possibly due to altered N-methyl-d-aspartate (NMDA) receptor function.

Objectives

We investigated whether memantine, an NMDA receptor antagonist, differentially influences impulsivity measures and Go/No-Go behavior and fMRI activity in matched FHP and FHN individuals.

Methods

On separate days, participants received a single dose of 40?mg memantine or identical-appearing placebo.

Results

No group performance differences were observed on placebo for Go correct hit or No-Go false alarm reaction time on the Go/No-Go task. During fMRI, right cingulate activation differed for FHP vs. FHN subjects during No-Go correct rejects. Memantine had attenuated effects in FHP vs. FHN subjects: For No-Go false alarms, memantine was associated with limited reduction in subcortical, cingulate, and temporal regions in FHP subjects and reduced activity in fronto-striatal?Cparietal networks in FHN subjects. For No-Go correct rejects, memantine (relative to placebo) reduced activity in left cingulate and caudate in FHP but not FHN subjects.

Conclusions

Lower sensitivity to the effects of memantine in FHP subjects is consistent with greater NMDA receptor function in this group.