Cognitive Function In Healthy Volunteers Research Articles

Psychedelics and cognitive function: A systematic review

Introduction: With the progressive advancement of clinical and experimental trials aimed at investigating the pharmacotherapeutic potential of psychedelic substances, there is also the development of other conceptions of use, not only for the treatment of psychiatric disorders, but also for the improvement of emotional/cognitive functions. Objective: The present study is a systematic review of investigations aimed at evaluating the effects of psychedelics on cognitive functions in healthy volunteers. Methods: A search was performed in PubMed database, using the search terms “psychedelics and cognitive enhancement” and “psychedelics and cognitive performance”. Results and conclusions: Of the experimental studies analyzed, only forty-six (46) met the inclusion criteria. The results obtained showed that 3,4-methylenedioxy-methamphetamine (MDMA) was the most studied drug, with eighteen (18) articles. Fourteen (14) articles were published with psilocybin. Lysergic acid diethylamide (LSD) ranked third, with six (6) articles; other two (2) studies focused on investigating the beverage ayahuasca, and another (1) its psychoactive-containing molecule: dimethyltryptamine (DMT). Eight (8) studies investigated the effects of other psychedelic drugs, like S-ketamine, mescaline, 3,4-methylenedioxy-amphetamine (MDE), and ibogaine. Although there were no serious adverse effects resulting from the use of the investigated psychedelic drugs, rigorous assessment of the potential risks of long-term use and of the advantages of the continuous use of these drugs through neuropsychological assessments are still warranted.

Clinical evaluation of a novel gallotannin-enriched Galla Rhois extract (GRE) on vital cognitive functions in healthy volunteers: A randomized, double-blind, placebo-controlled study

Background: Oxidative damage has emerged as one of the significant factors in the onset of neurodegenerative disorders, primarily owing to a) higher usage of oxygen by brain cells and b) higher amounts of lipids in the neuronal membranes. Together, these have resulted in higher susceptibility of brain cells to ROS-induced lipid peroxidation, damage to other cellular macromolecules, including nucleic acids and proteins, and death of neurons by apoptosis, ferroptosis, and necrosis. The design of therapeutics to prevent oxidative damage-induced brain stroke or other irreversible injuries has remained a challenge owing to the continuous production of free radicals at the site of damage. In this respect, plant-derived tannins and tannic acid derivatives have exhibited promising results in scavenging free radicals and inhibiting lipid peroxidation.Objective: This investigation reports the effect of Ghala Rois extract (GRE), a methyl gallate enriched gall formed on the nutgall sumac tree, Rhus javanica L. (Anacardiaceae), on enhancing the cognitive function and overall well-being through a double-blind, placebo-controlled, randomized, parallel-group design study on 80 healthy adult volunteers over a period of six consecutive weeks.Results: Administration of GRE in the dosage of 750 mg/day p.o. (with an equal amount of corn starch as a placebo) after breakfast resulted in significant improvement in cognitive functions as assessed by HappyNeuroPro, a digital therapy tool, and the cognitive tools under Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA) and Adult ADHD Self-Reported Scale (ASRSv1.1). Concomitantly, the GRE-treated subjects also scored significantly higher (p = 0.033) in the roles of Physical and Emotional Problems, Energy/Fatigue, Emotional well-being, and pain as evaluated by linearly independent pairwise comparisons among the estimated marginal means and computed using alpha = 0.05. In the Global Evaluation Questionnaire, over 77% of the treated subjects believed that the product increased their attention span, and helped their memory by 70%, and they also indicated their willingness to buy the commercially available GRE. Evaluation of the complete metabolic profile in the GRE-treated subjects significantly lowered the blood urea nitrogen (BUN) (11.98 mg/dL) as compared to placebo (13.27 mg/dL) (p = 0.011) as well as SGPT/ALT from 28.09 U/L (placebo) to 18.17 U/L (GRE-treated) (p<0.001). However, the vital parameters, including heart rate and systolic/diastolic pressure, were not affected by the consumption of GRE extract.Conclusion: The study demonstrated that GRE could be used as an effective new phytotherapeutic for reversing oxidative damage-induced neuronal degeneration and improving cognitive health in these study individuals.Keywords: Galla Rhois extract (GRE); Rhus javanica L. (family Anacardiaceae); Cognitive functions; ADHD; Executive function; Verbal memory; Safety, Reactive Oxygen Species (ROS)

Safety and Efficacy of a Novel Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Functions in Healthy Volunteers: A Clinical Investigation

Cognitive dysfunctions are increasing alarmingly around the world, and researchers are exploring preventive measures for improving brain performance. Pyrroloquinoline quinone (PQQ), a naturally occurring coenzyme in foods, exhibits potent antioxidant activity, and improves diverse functions which includes mitochondrial activation, growth, repair, protection of nerve cells by increased expression of nerve growth factor (NGF) and NGF receptors; and suppression of fibril formation and aggregation of amyloid β. A randomized, double‐blind, placebo‐controlled, parallel‐group clinical investigation (RCT) was conducted over a period of 12 weeks of supplementation of PQQ disodium salt (mnemoPQQ®; p.o.; 21.5 mg/day) in 64 healthy Japanese male and female volunteers (age 40 ‐ <80 Y) to determine the safety and efficacy on improved cognitive function and performance. In another independent study, mnemoPQQ® exhibited broad spectrum safety in a battery of toxicological assessments. No mutagenic potentials were observed. The efficacy of mnemoPQQ® on cognitive performance (memory, attention, judgment, and cognitive flexibility) was examined using Cognitrax as the primary outcome (endpoint), and forgetfulness questionnaire (DECO: Deterioration Cognitive Observee) and Mini‐Mental State Examination‐Japanese (MMSE‐J) as the secondary outcomes (endpoints). A total of 58 subjects (Placebo group = 31; Age = 70.91 ± 3.06 Y, and mnemoPQQ® group = 27; Age = 72.10 ± 3.77 Y) completed the study over a period of 12 weeks. Significant improvements were observed on the Cognitrax’s cognitive function domain score on “composite memory”, “verbal memory”, “reaction time”, “complex attention”, “cognitive flexibility”, “executive function”, and “motor speed” in the mnemoPQQ® group as compared to the placebo group. The DECO index and the MMSE‐J score were also significantly improved in the mnemoPQQ® group. No adverse events were reported. This investigation demonstrates that supplementation of mnemoPQQ® is safe and efficacious in improving memory, attention, judgment, and cognitive function, in middle‐aged to elderly population.

Effect of Bhramari Pranayama Practice on Cognitive Functions in Healthy Volunteers

Bhramari Pranayama (Humming bee breath) is one of the common slow pranayama practices, which involvesinhaling through both nostrils and while exhaling produce sound of humming bee. Practicing pranayama reducesthe effects of stress and strain on various systems by increasing the vagal tone. With the ongoing COVID-19pandemic, there are heightened feelings of stress, anxiety and depression and pranayama can be an effective wayto improve our mental and emotional well-being. This study has been chosen to assess the effect of Bhramaripranayama on cognitive functions and to compare the immediate and training effects of Bhramari pranayama inthe study group. An observational study was conducted among 110 students in a medical college aged between18-22 years for a period of 2 months. The participants were instructed to do 9 rounds of Bhramari Pranayama afterwhich the immediate effect of the Pranayama and 3 weeks of Pranayama practice on cognitive functions wasassessed. After training of Bhramari Pranayama for 3 weeks, a statistically significant improvement was observed.The study shows the possibility that Bhramari Pranayama has a beneficial effect on HRV in medical students, asthe autonomic balance shifts towards the improvement of parasympathetic tone. The study also showed betterattention, concentration and improved cognitive functions immediately after performing Bhramari pranayamawhich might be due to increased alertness and calmness.

Effect of Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study

Background Cognitive dysfunctions are increasing alarmingly around the world, and researchers are exploring preventive measures for improving brain performance. Pyrroloquinoline quinone (PQQ), a naturally occurring coenzyme in foods, exhibits potent antioxidant activity, and improves diverse functions which include mitochondrial activation, growth, repair, protection of nerve cells by increased expression of nerve growth factor (NGF) and NGF receptors; and suppression of fibril formation and aggregation of amyloid β. Objective This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of PQQ disodium salt powder (mnemoPQQ®) for improved cognitive function after 12 weeks of supplementation in healthy Japanese male and female (age 40 to <80 Y). Methods 64 healthy subjects were randomly assigned to receive either mnemoPQQ® (PQQ disodium salt: 21.5 mg/day) or a placebo over a period of 12 weeks. The efficacy of mnemoPQQ® on cognitive performance (memory, attention, judgment, and cognitive flexibility) was examined using Cognitrax as the primary outcome (primary endpoint), and forgetfulness questionnaire (DECO: Deterioration Cognitive Observee) and Mini-Mental State Examination-Japanese (MMSE-J) as the secondary outcome (secondary endpoint). Results A total of 58 subjects (placebo = 31; Age = 70.91 ± 3.06 Y; mnemoPQQ® group = 27; Age = 72.10 ± 3.77 Y) completed the study over a period of 12 weeks of supplementation. Significant improvements were observed on the Cognitrax’s cognitive function domain score on “composite memory”, “verbal memory”, “reaction time”, “complex attention”, “cognitive flexibility”, “executive function”, and “motor speed” in the mnemoPQQ® group as compared to the placebo group. The DECO and the MMSE-J scores were also significantly improved in the mnemoPQQ® group. No adverse events were observed. Conclusions Study demonstrates that supplementation of PQQ disodium salt is useful in improving memory, attention, judgment, and cognitive function, in middle-aged to elderly population, who feel they have become more forgetful because of aging.

Propofol Sedation Alters Perceptual and Cognitive Functions in Healthy Volunteers as Revealed by Functional Magnetic Resonance Imaging.

Elucidating networks underlying conscious perception is important to understanding the mechanisms of anesthesia and consciousness. Previous studies have observed changes associated with loss of consciousness primarily using resting paradigms. The authors focused on the effects of sedation on specific cognitive systems using task-based functional magnetic resonance imaging. The authors hypothesized deepening sedation would degrade semantic more than perceptual discrimination. Discrimination of pure tones and familiar names were studied in 13 volunteers during wakefulness and propofol sedation targeted to light and deep sedation. Contrasts highlighted specific cognitive systems: auditory/motor (tones vs. fixation), phonology (unfamiliar names vs. tones), and semantics (familiar vs. unfamiliar names), and were performed across sedation conditions, followed by region of interest analysis on representative regions. During light sedation, the spatial extent of auditory/motor activation was similar, becoming restricted to the superior temporal gyrus during deep sedation. Region of interest analysis revealed significant activation in the superior temporal gyrus during light (t [17] = 9.71, P < 0.001) and deep sedation (t [19] = 3.73, P = 0.001). Spatial extent of the phonologic contrast decreased progressively with sedation, with significant activation in the inferior frontal gyrus maintained during light sedation (t [35] = 5.17, P < 0.001), which didn't meet criteria for significance in deep sedation (t [38] = 2.57, P = 0.014). The semantic contrast showed a similar pattern, with activation in the angular gyrus during light sedation (t [16] = 4.76, P = 0.002), which disappeared in deep sedation (t [18] = 0.35, P = 0.731). Results illustrate broad impairment in cognitive cortex during sedation, with activation in primary sensory cortex beyond loss of consciousness. These results agree with clinical experience: a dose-dependent reduction of higher cognitive functions during light sedation, despite partial preservation of sensory processes through deep sedation.

Influence of dexmedetomidine on cognitive function in volunteers

Study objectiveSome outpatient procedures are performed under sedation with dexmedetomidine, although the effect of dexmedetomidine on cognitive function remains unclear. This study investigated the effect of dexmedetomidine on cognitive function in healthy volunteers. DesignObservation study in volunteers. SettingUniversity-affiliated teaching hospital. PatientsSix healthy volunteers. InterventionsAfter infusion of a 6-μg/kg per hour loading dose of dexmedetomidine for 10 minutes, a maintenance infusion of 0.4 μg/kg per hour was administered for 4 hours. MeasurementsCognitive function was evaluated before infusion (baseline) and at 2, 4, 6, and 8 hours after infusion. Cognitive function, response speed, accuracy, and consistency were measured by CogHealth. Depth of sedation was evaluated at 1-hour intervals by evaluating the Bispectral Index. Data are presented as the change from baseline. Main resultsThe Bispectral Index value was significantly lower from 10 minutes to 6 hours after infusion versus the pre-infusion value. Response speed was also significantly lower at 2 hours and 4 hours after infusion (92 ± 8%, P< .0001; 93 ± 6%, P< .0001), as was consistency (96 ± 7%, P= .0009; 96 ± 5%, P= .0003). Response accuracy was unaltered by the infusion. ConclusionsDexmedetomidine slightly reduced response speed and consistency, but did not affect response accuracy. Cognitive function was restored to pre-administration values 2 hours after the infusion of dexmedetomidine was discontinued.

Prism adaptation contrasts perceptual habituation for repetitive somatosensory stimuli

Prism adaptation (PA) is a non-invasive procedure that requires performing a visuo-motor pointing task while wearing prism goggles inducing a visual displacement of the pointed target. This procedure involves a reorganization of sensorimotor coordination, and induces long-lasting effects on numerous higher-order cognitive functions in healthy volunteers and neglect patients. Prismatic displacement (PD) of the visual field can be induced when prisms are worn but no sensorimotor task is required. In this case, it is unlikely that any subsequent reorganization takes place. The effects of PD are short-lived in the sense that they last as long as prisms are worn. In this study we aimed, to the best of our knowledge for the first time, at investigating whether PA and PD induce changes in the perception of intensity of nociceptive and non- nociceptive somatosensory stimuli. We induced, in healthy volunteers, PD (experiment 1), or PA (experiment 2) and asked participants to rate the intensity of the stimuli applied to the hand undergoing the visuo-proprioceptive conflict (experiment 1) or adaptation (experiment 2). Our results indicate that: 1) the visuo-proprioceptive conflict induced by PD does not reduce the perceived intensity of the stimuli, 2) PA prevents perceptual habituation for both nociceptive and non-nociceptive somatosensory stimuli. Moreover, to investigate the possible underlying mechanisms of the effects of PA we conducted a third experiment in which stimuli were applied both at the adapted and the non-adapted hand. In line with the results of experiment 2, we found that perceptual habituation was prevented for stimuli applied onto the adapted hand. Moreover, we observed the same finding for stimuli applied onto the non-adapted hand. This result suggests that the detention of habituation is not merely driven by changes in spatial attention allocation. Taken together, these data indicate that prisms can affect the perceived intensity of somatosensory stimuli, but only when PA is induced.

The effect of selective head-neck cooling on physiological and cognitive functions in healthy volunteers.

In general, brain temperatures are elevated during physical sporting activities; therefore, reducing brain temperature shortly after a sports-related concussion (SRC) could be a promising intervention technique. The main objective of this study was to examine the effects of head and neck cooling on physiological and cognitive function in normal healthy volunteers. Twelve healthy volunteers underwent two different sessions of combined head and neck cooling, one session with a cold pack and one session with a room temperature pack. Physiological measurements included: systolic/diastolic blood pressure, pulse oximetry, heart rate, and sublingual and tympanic temperature. Cognitive assessment included: processing speed, executive function, and working memory tasks. Physiological measurements were taken pre-, mid- and post-cooling, while cognitive assessments were done before and after cooling. The order of the sessions was randomized. There was a significant decrease in tympanic temperature across both sessions; however more cooling occurred when the cold pack was in the device. There was no significant decrease in sublingual temperature across either session. The observed heart rates, pulse oximetry, systolic and diastolic blood pressure during the sessions were all within range of a normal healthy adult. Cognitive assessment remained stable across each session for both pre- and post-cooling.We propose that optimizing brain temperature management after brain injury using head and neck cooling technology may represent a sensible, practical, and effective strategy to potentially enhance recovery and perhaps minimize the subsequent short and long term consequences from SRC.

Impairments of Spatial Working Memory and Attention Following Acute Psychosocial Stress

Few studies have investigated the effect of an acute psychosocial stress paradigm on impaired attention and working memory in humans. Further, the duration of any stress-related cognitive impairment remains unclear. The aim of this study was to examine the effect of an acute psychosocial stress paradigm, the Trier Social Stress, on cognitive function in healthy volunteers. Twenty-three healthy male and female subjects were exposed to an acute psychosocial stress task. Physiological measures (salivary cortisol, heart rate and blood pressure) and subjective stress ratings were measured at baseline, in anticipation of stress, immediately post-stress and after a period of rest. A neuropsychological test battery including spatial working memory and verbal memory was administered at each time point. Acute psychosocial stress produced significant increases in cardiovascular and subjective measures in the anticipatory and post-stress period, which recovered to baseline after rest. Salivary cortisol steadily declined over the testing period. Acute psychosocial stress impaired delayed verbal recall, attention and spatial working memory. Attention remained impaired, and delayed verbal recall continued to decline after rest. Acute psychosocial stress is associated with an impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in attention and memory.

Effect of Fast and Slow Pranayama Practice on Cognitive Functions in Healthy Volunteers

To compare the cumulative effect of commonly practised slow and fast pranayama on cognitive functions in healthy volunteers. 84 participants who were in self-reported good health, who were in the age group of 18-25 years, who were randomized to fast pranayama, slow pranayama and control group with 28 participants in each group. Fast pranayama included kapalabhati, bhastrika and kukkuriya. Slow pranayama included nadishodhana, Pranav and Savitri. Respective pranayama training was given for 35 minutes, three times per week, for a duration of 12 weeks under the supervision of a certified yoga trainer. Parameters were recorded before and after 12 weeks of intervention: Perceived stress scale (PSS), BMI, waist to hip ratio and cognitive parameters-letter cancellation test, trail making tests A and B, forward and reverse digit spans and auditory and visual reaction times for red light and green light. Inter-group comparison was done by one way ANOVA and intra-group comparison was done by paired t-test. Executive functions, PSS and reaction time improved significantly in both fast and slow pranayama groups, except reverse digit span, which showed an improvement only in fast pranayama group. In addition, percentage reduction in reaction time was significantly more in the fast pranayama group as compared to that in slow pranayama group. Both types of pranayamas are beneficial for cognitive functions, but fast pranayama has additional effects on executive function of manipulation in auditory working memory, central neural processing and sensory-motor performance.

The Effects of Exercise and Body Armor on Cognitive Function in Healthy Volunteers

Police officers routinely wear body armor to protect themselves against the threat posed by firearms and edged weapons, yet little is known of the cognitive effects of doing so. Two studies investigated the effects of exercise and body armor on working memory function in healthy volunteers. In study 1, male undergraduates were assigned to one of four groups: (i) brief exercise, (ii) brief exercise wearing body armor, (iii) extended exercise, and (iv) extended exercise wearing body armor. In study 2, university gym members were assigned to one of two groups: (i) wearing body armor and (ii) not wearing body armor. In both studies, heart rate and oral temperature were measured before, immediately after, and 5 minutes after exercise. The phonemic verbal fluency task and digits backward test were administered at the same time points. In both studies, a mixed analysis of variance revealed statistically significant changes to the cognitive functioning of participants. A change in cognitive strategy was observed, reflected by a decrease in executive function (switches) and an increase in nonexecutive function (cluster size). These data suggest that the cognitive effects of exercise and body armor may have profound implications for police officers' ability to make tactical decisions.

Effects of repeated dosing with mirtazapine, trazodone, or placebo on driving performance and cognitive function in healthy volunteers

This study aimed to evaluate the effects of repeated treatments with the sedative antidepressants mirtazapine and trazodone on driving performance and cognitive function. Nineteen healthy men received continuous nocturnal doses of 15-mg mirtazapine , 25-mg trazodone, or placebo for 8 days in a double-blinded, three-way crossover trial. Subjects were asked to perform three driving tasks (road tracking, car following, and harsh braking) using a driving simulator and cognitive tasks (the Wisconsin Card Sorting Test, Continuous Performance Test, and N-back Test) at baseline and on Days 2 and 9. Stanford Sleepiness Scale scores were also assessed. Mirtazapine significantly increased the standard deviation of lateral position in the road-tracking task as compared with trazodone on Day 2. Mirtazapine significantly increased Stanford Sleepiness Scale scores as compared with trazodone and placebo. For the remaining tasks, no significant effects of treatment were observed. Acute treatment of mirtazapine impaired road-tracking performance and increased sleepiness, but sedative effects disappeared under repeated administrations. Trazodone did not affect driving performance or cognitive function under acute or repeated administrations. Both initial sedative effects and pharmacological profiles should be taken into consideration when using sedative antidepressants.

Effects of modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers

BackgroundModafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions. The aim of this study was to investigate the effects of modafinil on non-verbal cognitive functions in healthy volunteers, with a particular focus on variations of cognitive load, measures of motivational factors and the effects on creative problem-solving. MethodsA double-blind placebo-controlled parallel design study evaluated the effect of 200 mg of modafinil (N = 32) or placebo (N = 32) in non-sleep deprived healthy volunteers. Non-verbal tests of divergent and convergent thinking were used to measure creativity. A new measure of task motivation was used, together with more levels of difficulty on neuropsychological tests from the CANTAB battery. ResultsImprovements under modafinil were seen on spatial working memory, planning and decision making at the most difficult levels, as well as visual pattern recognition memory following delay. Subjective ratings of enjoyment of task performance were significantly greater under modafinil compared with placebo, but mood ratings overall were not affected. The effects of modafinil on creativity were inconsistent and did not reach statistical significance. ConclusionsModafinil reliably enhanced task enjoyment and performance on several cognitive tests of planning and working memory, but did not improve paired associates learning. The findings confirm that modafinil can enhance aspects of highly demanding cognitive performance in non-sleep deprived individuals.This article is part of a Special Issue entitled ‘Cognitive Enhancers’.

The effects of acute treatment with tandospirone, diazepam, and placebo on driving performance and cognitive function in healthy volunteers

To assess the effects of two anxiolytics, diazepam and tandospirone, on driving performance from methodological viewpoints taking frequent rear-end collisions into account. In this double-blinded, three-way crossover trial, 18 healthy males received acute doses of 20 mg tandospirone (TSP), 5 mg diazepam (DZP), and placebo (PCB). The subjects were administered three driving tasks-road tracking, car following, and harsh braking-performed using a driving simulator and three cognitive tasks-Wisconsin Card Sorting Test, Continuous Performance Test, and N-back test-at baseline and at 1 and 4 h post-dosing. The Stanford Sleepiness Scale scores were also assessed. DZP nonsignificantly increased the percent change of brake reaction time (BRT) as compared to PCB at 4 h post-dosing. TSP nonsignificantly decreased the percent change of BRT as compared to PCB. Consequently, there was a significant difference in the percent change of BRT between DZP and TSP at 4 h post-dosing. For the remaining tasks, no statistically significant effects of treatment were observed. Acute doses of DZP significantly impaired the harsh-braking performance as compared to acute doses of TSP. These findings suggest that TSP may be used more safely in patients' driving activities.

The effects of the glycine reuptake inhibitor R213129 on the central nervous system and on scopolamine-induced impairments in psychomotor and cognitive function in healthy subjects

In this study the effects of R213129, a selective glycine transporter 1 inhibitor, on central nervous system function were investigated in healthy males in the absence and presence of scopolamine. This was a double-blind, placebo-controlled, 4-period crossover ascending dose study evaluating the following endpoints: body sway, saccadic and smooth pursuit eye movements, pupillometry, electroencephalography, visual analogue scales for alertness, mood, calmness and psychedelic effects, adaptive tracking, finger tapping, Visual and Verbal Learning Task, Stroop test, hormone levels and pharmacokinetics. R213129 dose levels were selected based on exposure levels that blocked the GlyT1 sites >50% in preclinical experiments. Forty-three of the 45 included subjects completed the study. Scopolamine significantly affected almost every central nervous system parameter measured in this study. R213129 alone compared with placebo did not elicit pharmacodynamic changes. R213129 had some small effects on scopolamine-induced central nervous system impairments. Scopolamine-induced finger tapping impairment was further enhanced by 3 mg R213129 with 2.0 taps/10 seconds (95% CI -4.0, -0.1), electroencephalography alpha power was increased by 10 mg R213129 with respectively 12.9% (0.7, 26.6%), scopolamine-induced impairment of the Stroop test was partly reversed by 10 mg R213129 with 59 milliseconds (-110, -7). Scopolamine produced robust and consistent effects in psychomotor and cognitive function in healthy volunteers. The most logical reason for the lack of R213129 effects seems to be that the central nervous system concentrations were too low. The effects of higher doses in healthy volunteers and the clinical efficacy in patients remain to be established.

Assessment of lithium ingestion on cognition and some subset of motor skill

Background:Patients taking lithium often report of difficulties in concentration, memory, learning, and attention. Laboratory tests of cognitive functions in healthy volunteers on chronic lithium demonstrate that disruptions in memory-learning processes are apparent at the time of memory retrieval.Aim:This study has attempted to evaluate the impact of lithium ingestion on cognition and some subset of sensory skill, by examining comparatively how lithium or a lithium / saline supplement either harms or helps the brain.Materials and Methods:Wistar Rats (male and female) were housed in individual improvised cages. The rats were acclimatized for two weeks after which they were randomly grouped into three, namely, control, lithium-treated, and lithium with saline-treated groups, and treated for four weeks. The lithium-treated group received 40 mM lithium bicarbonate per kg of feed for the first one week, and the dosage was increased to 60mM per kg of feed for the rest of the three weeks. The lithium-saline group received saline solution in addition to lithium. The control group was given normal feed and water liberally for the period of the experiment. The rats were subjected to a cognitive test using the Barnes maze, assessments of negative geotaxis, cliff avoidance, and some neurotransmitters (acetylcholine and glutamate). The data were analyzed by Microsoft excel 2007.Results:This study shows that lithium ingestion is characterized by a significant (P ≤ 0.05) decline in learning and memory as compared to the control. While the lithium-saline-treated animals exhibit enhanced cognitive ability. The subset of sensory activity was assessed; negative geotaxis and cliff avoidance were grossly compromised, thus lithium carbonate appeared to have definite negative effects on the psychsensory speed.Conclusion:In conclusion lithium should be co-administered with saline to counter the detrimental effects of lithium noticed in this study, which include impairment of tasks on psychomotor speed and cognition.

P4-352: The role of nicotinic receptors in human cognitive function

In the 1970's evidence began to accumulate that nicotine was able to improve aspects of cognitive function in healthy volunteers. The definitive studies involved the administration of nicotine to non-smokers and required sensitive automated tests to identify these effects. This early work has been extensively replicated, and it is now widely accepted that nicotine improves various aspects of human attention and information processing. However, the evidence that nicotine can improve episodic memory in man remains weak. As the attentional enhancement produced by nicotine in volunteers can be blocked by scopolamine but not by haloperidol, this strongly supports a cholinergic mechanism underlying these effects. Such work has led to a closer scrutiny of the profile of cognitive deficits in dementias with a cholinergic basis, including Alzheimer's disease, Dementia with Lewy Bodies and Parkinson's dementia. Studies have shown attentional deficits to be central to all of the dementias with a cholinergic basis. Interest in nicotine has now given over to the selective receptor antagonists. Trials of α7 nicotinic agonists (eg GTS-21, MEM 3454) have found that besides enhancing attention in volunteers, these compounds also improve aspects of episodic secondary memory. A similar profile of effects has emerged from trials with α4β2 nicotinic agonists (eg TC-1734/AZD-3480). The therapeutic potential of these findings has now been confirmed, TC-1734/AZD-3480 has shown the ability to improve attention and memory in both AAMI and MCI populations, and MEM-3454 in Alzheimer's patients. This work which spans three and a half decades will be reviewed. Some possible explanations for the broader range of cognitive effects of more specific receptor agonists will be considered.

Erythropoietin Improves Mood and Modulates the Cognitive and Neural Processing of Emotion 3 Days Post Administration

Erythropoietin (Epo) has neuroprotective and neurotrophic effects and is a promising candidate for treatment of neurodegenerative and psychiatric disorder. Recently, we demonstrated that Epo modulates memory-relevant hippocampal response and fear processing in human models of antidepressant drug action 1 week post-administration, and improves self-reported mood for 3 days immediately following administration. The present study explored the effects of Epo (40 000 IU) vs saline on self-reported mood and on neural and cognitive function in healthy volunteers 3 days post-administration to test the reliability of the rapid mood improvement and its neuropsychological basis. Neuronal responses during the processing of happy and fearful faces were investigated using functional magnetic resonance imaging (fMRI); facial expression recognition performance was assessed after the fMRI scan. Daily ratings of mood were obtained for 3 days after Epo/saline administration. During faces processing Epo enhanced activation in the left amygdala and right precuneus to happy and fearful expressions. This was paired with improved recognition of all facial expressions, in particular of low intensity happiness and fear. This is similar to behavioral effects observed with acute administration of serotonergic antidepressants. Consistent with our previous finding, Epo improved self-reported mood for all 3 days post-administration. Together, these results suggest that characterization of the effects of Epo in a clinically depressed group is warranted.

Lorazepam 0.25 mg twice a day improves aspects of psychometric performance in healthy volunteers

The effects of lorazepam (0.25 mg) twice a day on several cognitive and performance tasks, pictures test, digit-symbol substitution test (DSST), choice reaction time (CRT) and critical flicker fusion (CFF), were investigated in healthy students. A double-blind independent group design was used to compare placebo and lorazepam (30 volunteers in each group). After randomisation, all subjects received placebo for 3 days (D), followed by 14 days of treatment, with either lorazepam or placebo. Subjects completed a battery of tests at Do, then D(3), D(7) , D(10) and D(14). D(3) performance was poorer in the lorazepam group except for CFF (ascending values and total values), yet the only significant improvement was in total reaction time on the CRT test. However, a significant improvement of performance was shown at D(7), D(10) and D(14) in the lorazepam group compared with the control group (except in recognition reaction time). The current study shows that low repeated doses of lorazepam are able to produce small improvements in some aspects of psychomotor and cognitive functions in healthy volunteers. Different points are discussed to explain the performance improvement: training effect, tolerance effect, partial inverse agonist effect and the possible release of cholecystokinin.