ABSTRACT
Inositol stabilized arginine silicate (ASI) ingestion has been reported to increase nitric oxide levels while inositol (I) has been reported to enhance neurotransmission. The current study examined whether acute ASI + I (Inositol-enhanced bonded arginine silicate) ingestion affects cognitive function in e-sport gamers. In a double blind, randomized, placebo controlled, and crossover trial, 26 healthy male (n = 18) and female (n = 8) experienced gamers (23 ± 5 years, 171 ± 11 cm, 71.1 ± 14 kg, 20.7 ± 3.5 kg/m2) were randomly assigned to consume 1600 mg of ASI + I (nooLVL®, Nutrition 21) or 1600 mg of a maltodextrin placebo (PLA). Prior to testing, participants recorded their diet, refrained from consuming atypical amounts of stimulants and foods high in arginine and nitrates, and fasted for 8 h. During testing sessions, participants completed stimulant sensitivity questionnaires and performed cognitive function tests (i.e., Berg-Wisconsin Card Sorting task test, Go/No-Go test, Sternberg Task Test, Psychomotor Vigilance Task Test, Cambridge Brain Sciences Reasoning and Concentration test) and a light reaction test. Participants then ingested treatments in a randomized manner. Fifteen minutes following ingestion, participants repeated tests (Pre-Game). Participants then played their favorite video game for 1-h and repeated the battery of tests (Post-Game). Participants observed a 7-14-day washout period and then replicated the study with the alternative treatment. Data were analyzed by General Linear Model (GLM) univariate analyses with repeated measures using weight as a covariate, paired t-tests (not adjusted to weight), and mean changes from baseline with 95% Confidence Intervals (CI). Pairwise comparison revealed that there was a significant improvement in Sternberg Mean Present Reaction Time (ASI + I vs. PLA; p < 0.05). In Post-Game assessments, 4-letter Absent Reaction Time (p < 0.05), 6-letter Present Reaction Time (p < 0.01), 6-letter Absent Reaction Time (p < 0.01), Mean Present Reaction Time (p < 0.02), and Mean Absent Reaction Time (p < 0.03) were improved with ASI + I vs. PLA. There was a non-significant trend in Pre-Game Sternberg 4-letter Present Reaction time in ASI + I vs. PLA (p < 0.07). ASI + I ingestion better maintained changes in Go/No-Go Mean Accuracy and Reaction Time, Psychomotor Vigilance Task Reaction Time, and Cambridge Post-Game Visio-spatial Processing and Planning. Results provide evidence that ASI + I ingestion prior to playing video games may enhance some measures of short-term and working memory, reaction time, reasoning, and concentration in experienced gamers.
Subject(s)
Arginine/administration & dosage , Cognition/drug effects , Dietary Supplements , Executive Function/drug effects , Inositol/administration & dosage , Silicates/administration & dosage , Video Games/psychology , Adult , Attention/drug effects , Cross-Over Studies , Double-Blind Method , Drug Combinations , Female , Healthy Volunteers , Humans , Male , Memory, Short-Term/drug effects , Neuropsychological Tests , Problem Solving/drug effects , Reaction Time/drug effects , Young AdultABSTRACT
Cognition is a crucial element of human functionality. Like any other physical capability, cognition is both enabled and limited by tissue biology. The aim of this study was to investigate whether oxygen is a rate-limiting factor for any of the main cognitive domains in healthy young individuals. Fifty-six subjects were randomly assigned to either increased oxygen supply using hyperbaric oxygen (two atmospheres of 100% oxygen) or to a "sham" treatment (a simulation of increased pressure in a chamber with normal air). While in the chamber, participants went through a battery of tests evaluating the major cognitive domains including information processing speed, episodic memory, working memory, cognitive flexibility, and attention. The results demonstrated that from all evaluated cognitive domains, a statistically significant improvement was found in the episodic memory of the hyper-oxygenized group. The hyper-oxygenized group demonstrated a better learning curve and a higher resilience to interference. To conclude, oxygen delivery is a rate-limiting factor for memory function even in healthy young individuals under normal conditions. Understanding the biological limitations of our cognitive functions is important for future development of interventional tools that can be used in daily clinical practice.
Subject(s)
Cognition/drug effects , Hyperbaric Oxygenation/methods , Memory, Episodic , Mental Recall/drug effects , Oxygen/administration & dosage , Psychomotor Performance/drug effects , Adult , Attention/drug effects , Attention/physiology , Cognition/physiology , Female , Humans , Male , Mental Recall/physiology , Oxygen/metabolism , Problem Solving/drug effects , Problem Solving/physiology , Prospective Studies , Psychomotor Performance/physiology , Treatment Outcome , Young AdultABSTRACT
To reveal new insights into statin cognitive effects, we performed an observational study on a population-based sample of 245,731 control and 55,114 statin-taking individuals from the UK Biobank. Cognitive performance in terms of reaction time, working memory and fluid intelligence was analysed at baseline and two follow-ups (within 5-10 years). Subjects were classified depending on age (up to 65 and over 65 years) and treatment duration (1-4 years, 5-10 years and over 10 years). Data were adjusted for health- and cognition-related covariates. Subjects generally improved in test performance with repeated assessment and middle-aged persons performed better than older persons. The effect of statin use differed considerably between the two age groups, with a beneficial effect on reaction time in older persons and fluid intelligence in both age groups, and a negative effect on working memory in younger subjects. Our analysis suggests a modulatory impact of age on the cognitive side effects of statins, revealing a possible reason for profoundly inconsistent findings on statin-related cognitive effects in the literature. The study highlights the importance of characterising modifiers of statin effects to improve knowledge and shape guidelines for clinicians when prescribing statins and evaluating their side effects in patients.
Subject(s)
Cognition Disorders/diagnosis , Cognition/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hypercholesterolemia/drug therapy , Age Factors , Aged , Case-Control Studies , Cognition Disorders/chemically induced , Female , Follow-Up Studies , Humans , Male , Memory, Short-Term/drug effects , Middle Aged , Neuropsychological Tests , Problem Solving/drug effects , Reaction Time/drug effects , United KingdomABSTRACT
Omega-3 fatty acids are vital for brain development. The aim of this meta-analysis was to broaden current knowledge of the effects of omega-3 supplementation on cognitive test performance in youths. Randomized controlled trials (RCTs) meeting selection criteria were identified through two independent literature searches on PubMed, Cochrane Library, PsycARTICLES and PsycINFO (last search June 2019). Twenty-nine out of 1126 studies assessing 4247 participants met all selection criteria. A meta-analysis using random-effects model was performed for eight different cognitive domains. This first analysis revealed no main effect of omega-3 fatty acid supplementation on domain-specific cognitive test performance in youths. Subgroup analyses identified beneficial effects of eicosapentaenoic acid (EPA)-rich but not docosahexaenoic acid (DHA)-rich formulations in the domains of long-term memory, working memory and problem solving and a tendency towards beneficial effects in clinical rather than non-clinical populations. Future research should investigate differential effects of EPA and DHA and consider their baseline levels, other nutritional components and interactions with gene variations as potential predictors of response.
Subject(s)
Cognition/drug effects , Docosahexaenoic Acids/pharmacology , Eicosapentaenoic Acid/pharmacology , Memory/drug effects , Problem Solving/drug effects , Psychomotor Performance/drug effects , Adolescent , Child , HumansABSTRACT
Caffeine is the most widely consumed psychotropic drug in the world, with numerous studies documenting the effects of caffeine on people's alertness, vigilance, mood, concentration, and attentional focus. The effects of caffeine on creative thinking, however, remain unknown. In a randomized placebo-controlled between-subject double-blind design the present study investigated the effect of moderate caffeine consumption on creative problem solving (i.e., convergent thinking) and creative idea generation (i.e., divergent thinking). We found that participants who consumed 200 mg of caffeine (approximately one 12 oz cup of coffee, n = 44), compared to those in the placebo condition (n = 44), showed significantly enhanced problem-solving abilities. Caffeine had no significant effects on creative generation or on working memory. The effects remained after controlling for participants' caffeine expectancies, whether they believed they consumed caffeine or a placebo, and changes in mood. Possible mechanisms and future directions are discussed.
Subject(s)
Caffeine/pharmacology , Central Nervous System Stimulants/pharmacology , Creativity , Problem Solving/drug effects , Thinking/drug effects , Adolescent , Adult , Affect/drug effects , Caffeine/administration & dosage , Central Nervous System Stimulants/administration & dosage , Double-Blind Method , Female , Humans , Male , Memory, Short-Term/drug effects , Young AdultABSTRACT
A growing body of research suggests that hormonal contraceptive (HC) use may be associated with lower self-control, as well as structural and functional differences in women's brains that could contribute to differences in perseverance on tasks requiring cognitive control. Here, we sought to extend this research by examining the relationship between HC use and college-aged women's perseverance (i.e., time spent) and performance on tasks requiring cognitive control. Across two studies, we find that, compared to naturally-cycling women, women using HCs display less perseverance on both simple (i.e., a spot-the-difference game) and challenging (i.e., Graduate Record Examination quantitative problems) tasks. Moreover, these differences in perseverance were found to predict performance decrements across tasks, with women taking HCs performing worse because they spent less time on the tasks. By demonstrating how HC use may influence perseverance and thereby performance, these results contribute to a growing body of research examining the unintended implications of HC use on cognition, learning, and memory.
Subject(s)
Adaptation, Psychological/drug effects , Cognition/drug effects , Contraceptives, Oral, Hormonal/therapeutic use , Executive Function/drug effects , Resilience, Psychological/drug effects , Adult , Brain/drug effects , Brain/physiology , Cognition/physiology , Female , Humans , Problem Solving/drug effects , Psychometrics , Psychomotor Performance/drug effects , Psychomotor Performance/physiology , Self Concept , Self-Control/psychology , Young AdultABSTRACT
INTRODUCTION: Patients with schizophrenia are mainly characterized by negative symptoms and cognitive dysfunction. In this proof-of-concept study we tested effects on cognition and negative symptoms of a 6- or 24-week memantine add-on treatment to risperidone in patients with acute or chronic schizophrenia. MATERIALS AND METHODS: Patients with an acute episode of schizophrenia (n=11) and predominating positive symptoms were randomized to a 6-week add-on treatment with memantine (10 mg twice a day) versus placebo and patients with chronic schizophrenia (n=13) and negative symptoms were randomized to a 24-week add-on treatment with memantine (10 mg twice a day) versus placebo. All patients received antipsychotic medication with risperidone (2-8 mg/day). Psychopathological changes were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 2, 4, 6, 12, and 24 weeks. Cognitive function was measured at baseline, after 6 weeks, and 24 weeks. RESULTS: Patients with acute schizophrenia who received add-on treatment with memantine showed a significantly higher performance in attention intensity (p=0.043), problem-solving (p=0.043), verbal learning (p=0.050), and flexibility (p=0.049). Patients with chronic schizophrenia showed a significantly higher immediate memory in the memantine group compared to the placebo group (p=0.033) and a significantly greater reduction of the PANSS sum score if compared to the placebo group. DISCUSSIONS: Our study gives further evidence that memantine add-on treatment to risperidone may have neuroprotective effects and improve cognitive function in patients with schizophrenia. ClinicalTrials.gov Number: NCT00148590 and NCT00148616.
Subject(s)
Antipsychotic Agents/therapeutic use , Memantine/therapeutic use , Risperidone/therapeutic use , Schizophrenia/drug therapy , Acute Disease , Adult , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Attention/drug effects , Chronic Disease , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Memantine/administration & dosage , Memantine/adverse effects , Memory/drug effects , Problem Solving/drug effects , Prospective Studies , Psychiatric Status Rating Scales , Risperidone/administration & dosage , Risperidone/adverse effects , Socioeconomic Factors , Verbal Learning/drug effects , Young AdultABSTRACT
INTRODUCTION: Taking microdoses (a mere fraction of normal doses) of psychedelic substances, such as truffles, recently gained popularity, as it allegedly has multiple beneficial effects including creativity and problem-solving performance, potentially through targeting serotonergic 5-HT2A receptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics, it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults. METHODS: During a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were expected to be manifested. RESULTS: We found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected. CONCLUSION: While this study provides quantitative support for the cognitive-enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results, we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.
Subject(s)
Creativity , Hallucinogens/administration & dosage , Nootropic Agents/administration & dosage , Thinking/drug effects , Adult , Clinical Trials, Phase I as Topic , Dose-Response Relationship, Drug , Female , Humans , Intelligence/drug effects , Intelligence/physiology , Intelligence Tests , Male , Motivation/drug effects , Motivation/physiology , Photic Stimulation/methods , Problem Solving/drug effects , Problem Solving/physiology , Thinking/physiology , Young AdultABSTRACT
Heart rate variability (HRV) refers to variation in the interval between successive heart beats. Low HRV is an indicator of potential autonomic nervous system dysfunction. People with chronic pain often display autonomic dysregulation, especially in the parasympathetic nervous system. The hormone oxytocin has been shown to increase HRV in non-clinical samples, but its potential impact on HRV in persons with chronic pain is unknown. This study investigated the impact of intranasal oxytocin on HRV in persons with chronic neck and shoulder pain. Participants included 24 individuals with chronic neck and shoulder pain lasting >12months and 24 age- and sex-matched pain-free controls. In a randomised double-blind, placebo-controlled, cross-over study, participants self-administered intranasal oxytocin (24IU) in one session, and placebo in another, before HRV was recorded at rest and during a mental arithmetic task. Intranasal oxytocin did not influence HRV at rest. However, compared to placebo, intranasal oxytocin elicited small decreases in low-frequency and high-frequency HRV in both groups during the mental arithmetic task. These results suggest that intranasal oxytocin may enhance the salience of the mental arithmetic task, leading to reduced engagement of the parasympathetic nervous system when completing the task. Further investigation and replication of these findings are required to improve our understanding of the effects of intranasal oxytocin on autonomic functioning both at rest and under cognitive stress.
Subject(s)
Chronic Pain/drug therapy , Heart Rate/drug effects , Mathematical Concepts , Oxytocin/administration & dosage , Psychotropic Drugs/administration & dosage , Stress, Psychological/drug therapy , Administration, Intranasal , Adult , Autonomic Nervous System/drug effects , Autonomic Nervous System/physiology , Autonomic Nervous System/physiopathology , Chronic Pain/physiopathology , Chronic Pain/psychology , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Neck Pain/drug therapy , Neck Pain/physiopathology , Neck Pain/psychology , Neuropsychological Tests , Problem Solving/drug effects , Problem Solving/physiology , Self Administration , Shoulder Pain/drug therapy , Shoulder Pain/physiopathology , Shoulder Pain/psychology , Stress, Psychological/physiopathologyABSTRACT
The aim of the current study was to assess the influences of valproate (VPA) on the language functions in newly diagnosed pediatric patients with epilepsy. We reviewed medical records of 53 newly diagnosed patients with epilepsy, who were being treated with VPA monotherapy (n=53; 22 male patients and 31 female patients). The subjects underwent standardized language tests, at least twice, before and after the initiation of VPA. The standardized language tests used were The Test of Language Problem Solving Abilities, a Korean version of The Expressive/Receptive Language Function Test, and the Urimal Test of Articulation and Phonology. Since all the patients analyzed spoke Korean as their first language, we used Korean language tests to reduce the bias within the data. All the language parameters of the Test of Language Problem Solving Abilities slightly improved after the initiation of VPA in the 53 pediatric patients with epilepsy (mean age: 11.6±3.2years), but only "prediction" was statistically significant (determining cause, 14.9±5.1 to 15.5±4.3; making inference, 16.1±5.8 to 16.9±5.6; prediction, 11.1±4.9 to 11.9±4.2; total score of TOPS, 42.0±14.4 to 44.2±12.5). The patients treated with VPA also exhibited a small extension in mean length of utterance in words (MLU-w) when responding, but this was not statistically significant (determining cause, 5.4±2.0 to 5.7±1.6; making inference, 5.8±2.2 to 6.0±1.8; prediction, 5.9±2.5 to 5.9±2.1; total, 5.7±2.1 to 5.9±1.7). The administration of VPA led to a slight, but not statistically significant, improvement in the receptive language function (range: 144.7±41.1 to 148.2±39.7). Finally, there were no statistically significant changes in the percentage of articulation performance after taking VPA. Therefore, our data suggested that VPA did not have negative impact on the language function, but rather slightly improved problem-solving abilities.
Subject(s)
Anticonvulsants/adverse effects , Epilepsy/drug therapy , Epilepsy/psychology , Language , Valproic Acid/adverse effects , Adolescent , Anticonvulsants/therapeutic use , Child , Child, Preschool , Cognition , Dose-Response Relationship, Drug , Drug Administration Schedule , Epilepsy/diagnosis , Female , Humans , Language Tests , Male , Medical Records , Problem Solving/drug effects , Prospective Studies , Republic of Korea , Retrospective Studies , Treatment Outcome , Valproic Acid/therapeutic useABSTRACT
Study Objectives: To examine the duration and frequency of wake bouts underlying the wakefulness-after-sleep-onset (WASO) reduction with suvorexant. Methods: We analyzed polysomnogram recordings from clinical trials involving 1518 insomnia patients receiving suvorexant (40/30, 20/15 mg) or placebo to determine the following: (1) the number of, and time spent in, long or short wake bouts and (2) the association between sleep quality and bout characteristics. We also compared wake and sleep bout characteristics of suvorexant in insomnia patients versus zolpidem in healthy subjects undergoing experimentally induced transient insomnia. Results: Relative to placebo, suvorexant decreased the number and time spent in long wake bouts (>2 minutes) and increased the number and time spent in short wake bouts (≤2 minutes). The time spent in long wake bouts during Night-1 decreased by 32-54 minutes, whereas the time spent in short wake bouts increased by 2-6 minutes. On average, a patient returned to sleep from his or her longest awakening more than twice as fast on suvorexant than placebo. The reduced time spent in long wake bouts resulted in odds ratios of self-reported good or excellent sleep quality ranging from 1.59 to 2.19 versus placebo. The small increase in time spent in short wake bouts had no effect on odds ratios. Findings were more pronounced for the higher (40/30 mg) doses of suvorexant. The wake and sleep bout characteristics of suvorexant differed from zolpidem which equally decreased the number of wake and sleep bouts of all durations during the early part of the night. Conclusion: Suvorexant reduces WASO by reducing long wake bouts. This reduction has a positive effect on sleep quality. Clinical Trials: Trial registration at www.clinicaltrials.gov NCT01097616; NCT01097629.
Subject(s)
Azepines/therapeutic use , Orexin Receptor Antagonists/therapeutic use , Sleep Aids, Pharmaceutical/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep/drug effects , Triazoles/therapeutic use , Wakefulness/drug effects , Aged , Data Collection , Double-Blind Method , Female , Healthy Volunteers , Humans , Male , Placebos/therapeutic use , Polysomnography/drug effects , Problem Solving/drug effects , Self Report , Zolpidem/therapeutic useABSTRACT
RATIONALE AND OBJECTIVES: Norepinephrine mediates the adjustment of error-driven learning to match the rate of change of the environment, while phasic dopamine signals prediction errors. We tested the hypothesis that pharmacologic manipulation may modulate this process. METHODS: We administered a single dose of methylphenidate, a norepinephrine/dopamine reuptake inhibitor, or placebo in double-blind randomized fashion to 20 healthy human males, who then performed a probabilistic learning task. Each subject was tested in two sessions, receiving methylphenidate in one session and placebo in the other, in randomized order. Task performance was quantified by the percentage of trials on which subjects chose the most likely option, while learning rate was measured using a computational model-based parameter as well as with a behavioral analogue of this parameter. RESULTS: There was a substance-by-session interaction effect on behavioral learning rate and model-based learning rate, such that subjects receiving methylphenidate exhibited higher learning rates than those receiving placebo in session 1, with no difference observed in session 2, suggesting that subjects retained the increased learning rate across sessions. Higher behavioral learning rate was associated with both higher task performance and with the model-based learning rate. Higher learning rates were advantageous given the high rate of change on the task. Subjects receiving methylphenidate and placebo began the task in session 1 with a similar behavioral learning rate, but those receiving methylphenidate rapidly increased learning rate toward the optimal value, suggesting that methylphenidate accelerated the adaptation of learning rate based on the environment. CONCLUSIONS: The results suggest that methylphenidate may improve disrupted probabilistic learning in disorders involving noradrenergic or dopaminergic dysfunction.
Subject(s)
Learning Curve , Methylphenidate/pharmacology , Motivation/drug effects , Probability Learning , Problem Solving/drug effects , Adult , Double-Blind Method , Humans , Male , Patient-Specific Modeling , Task Performance and Analysis , Young AdultABSTRACT
Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system (CNS) development, such sensitive periods shape the formation of neuro-circuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint, as well as the environmental context. While allowing for adaptation, such sensitive periods are also windows of vulnerability during which external and internal factors can confer risk to brain disorders by derailing adaptive developmental programs. Our group has been particularly interested in developmental periods that are sensitive to serotonin (5-HT) signaling, and impact behavior and cognition relevant to psychiatry. Specifically, we review a 5-HT-sensitive period that impacts fronto-limbic system development, resulting in cognitive, anxiety, and depression-related behaviors. We discuss preclinical data to establish biological plausibility and mechanistic insights. We also summarize epidemiological findings that underscore the potential public health implications resulting from the current practice of prescribing 5-HT reuptake inhibiting antidepressants during pregnancy. These medications enter the fetal circulation, likely perturb 5-HT signaling in the brain, and may be affecting circuit maturation in ways that parallel our findings in the developing rodent brain. More research is needed to better disambiguate the dual effects of maternal symptoms on fetal and child development from the effects of 5-HT reuptake inhibitors on clinical outcomes in the offspring. Birth Defects Research 109:924-932, 2017. © 2017 Wiley Periodicals, Inc.
Subject(s)
Brain/drug effects , Serotonin and Noradrenaline Reuptake Inhibitors/adverse effects , Serotonin and Noradrenaline Reuptake Inhibitors/pharmacokinetics , Animals , Antidepressive Agents/pharmacology , Anxiety/chemically induced , Brain/embryology , Child , Child Development/drug effects , Cognition/drug effects , Depression/chemically induced , Depressive Disorder/drug therapy , Disease Models, Animal , Female , Humans , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/metabolism , Problem Solving/drug effects , Receptors, Serotonin, 5-HT1 , Serotonin/pharmacology , Selective Serotonin Reuptake Inhibitors/pharmacologyABSTRACT
Anecdotal reports link alcohol intoxication to creativity, while cognitive research highlights the crucial role of cognitive control for creative thought. This study examined the effects of mild alcohol intoxication on creative cognition in a placebo-controlled design. Participants completed executive and creative cognition tasks before and after consuming either alcoholic beer (BAC of 0.03) or non-alcoholic beer (placebo). Alcohol impaired executive control, but improved performance in the Remote Associates Test, and did not affect divergent thinking ability. The findings indicate that certain aspects of creative cognition benefit from mild attenuations of cognitive control, and contribute to the growing evidence that higher cognitive control is not always associated with better cognitive performance.
Subject(s)
Central Nervous System Depressants/pharmacology , Creativity , Ethanol/pharmacology , Executive Function/drug effects , Inhibition, Psychological , Thinking/drug effects , Adult , Alcoholic Intoxication/physiopathology , Beer , Central Nervous System Depressants/administration & dosage , Ethanol/administration & dosage , Female , Humans , Male , Problem Solving/drug effects , Young AdultABSTRACT
Impaired function of prefrontal brain networks may be the source of both negative symptoms and neurocognitive problems in psychotic disorders. Whereas most antipsychotics may decrease prefrontal activation, the partial dopamine D2-receptor agonist aripiprazole is hypothesized to improve prefrontal function. This study investigated whether patients with a psychotic disorder would show stronger activation of prefrontal areas and associated regions after treatment with aripiprazole compared to risperidone treatment. In this exploratory pharmacological neuroimaging study, 24 patients were randomly assigned to either aripiprazole or risperidone. At baseline and after nine weeks treatment they underwent an interview and MRI session. Here we report on brain activation (measured with arterial spin labeling) during performance of two tasks, the Tower of London and the Wall of Faces. Aripiprazole treatment decreased activation of the middle frontal, superior frontal and occipital gyrus (ToL) and medial temporal and inferior frontal gyrus, putamen and cuneus (WoF), while activation increased after risperidone. Activation increased in the ventral anterior cingulate and posterior insula (ToL), and superior frontal, superior temporal and precentral gyrus (WoF) after aripiprazole treatment and decreased after risperidone. Both treatment groups had increased ventral insula activation (ToL) and middle temporal gyrus (WoF), and decreased occipital cortex, precuneus and caudate head activation (ToL) activation. In conclusion, patients treated with aripiprazole may need less frontal resources for planning performance and may show increased frontotemporal and frontostriatal reactivity to emotional stimuli. More research is needed to corroborate and extend these preliminary findings.
Subject(s)
Antipsychotic Agents/therapeutic use , Aripiprazole/therapeutic use , Brain/drug effects , Risperidone/therapeutic use , Schizophrenia/drug therapy , Adult , Brain/diagnostic imaging , Brain/physiopathology , Brain Mapping , Emotions , Female , Humans , Interview, Psychological , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Problem Solving/drug effects , Problem Solving/physiology , Schizophrenia/diagnostic imaging , Schizophrenia/physiopathology , Schizophrenic Psychology , Single-Blind Method , Social Perception , Treatment OutcomeABSTRACT
Although neuropsychological studies have demonstrated specific cognitive impairments in children with childhood absence epilepsy (CAE), the potential role of the frontal lobe in these cognitive deficits remains unclear. We therefore evaluated cognitive functions related to and unrelated to the functionality of the frontal lobe in childhood absence epilepsy patients and control subjects. Thirty-seven childhood absence epilepsy patients and 37 age- and gender-matched healthy control subjects were recruited and assessed using a computerized neuropsychological test battery. Childhood absence epilepsy patients, especially a drug-naïve subgroup, showed cognitive deficits in reasoning, visual attention, and executive function, which are typical cognitive functions of the frontal lobe. In contrast, treated childhood absence epilepsy patients only exhibited cognitive deficits in visual attention. There were no significant between-group differences for other cognitive tests. Our findings suggest that frontal lobe-related cognitive deficits represent the characteristic neuropsychological profile associated with childhood absence epilepsy.
Subject(s)
Attention , Cognition , Epilepsy, Absence/psychology , Visual Perception , Adolescent , Anticonvulsants/therapeutic use , Attention/drug effects , Child , Child, Preschool , Cognition/drug effects , Cognition Disorders/etiology , Diagnosis, Computer-Assisted , Epilepsy, Absence/drug therapy , Executive Function/drug effects , Female , Humans , Male , Neuropsychological Tests , Problem Solving/drug effects , Visual Perception/drug effectsABSTRACT
Autism spectrum disorder (ASD) is characterized by impairments in social communication as well as restricted, repetitive behaviors. Evidence suggests that some individuals with ASD have cognitive impairments related to weak central coherence and hyperrestricted processing. Reducing noradrenergic activity may improve aspects of network processing and thus improve cognitive abilities, such as verbal problem solving, in individuals with ASD. The present pilot study explores the effects of acute administration of the beta-adrenergic antagonist propranolol on verbal problem solving in adults and adolescents with ASD. In a within-subject crossover-design, 20 participants with ASD received a single dose of propranolol or placebo on one of two sessions in a double-blinded, counterbalanced manner. Verbal problem solving was assessed via an anagram task. Baseline measurements of autonomic nervous system functioning were obtained, and anxiety was assessed at baseline and following drug administration. Participants solved the anagrams more quickly in the propranolol condition, as compared to the placebo condition, suggesting a potential cognitive benefit of this agent. Additionally, we observed a negative linear relationship between response to propranolol on the anagram task and two measures of baseline autonomic activity, as well as a positive linear relationship between drug response and baseline anxiety. These relationships propose potential markers for treatment response, as propranolol influences both autonomic functioning and anxiety. Further investigation is needed to expand on the present single-dose psychopharmacological challenge and explore the observed effects of propranolol in a serial-dose setting.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Autism Spectrum Disorder/drug therapy , Autism Spectrum Disorder/psychology , Problem Solving/drug effects , Propranolol/therapeutic use , Verbal Behavior/drug effects , Adolescent , Adult , Anxiety/psychology , Autonomic Nervous System/drug effects , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Pilot Projects , Psychomotor Performance/drug effects , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Bipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underlying these behaviors. Here, we investigated putative mechanisms underlying cognition and reward-seeking/motivational changes relevant to BD mania patients using two validated mouse models and neurochemical analyses. METHODS: The effects of reducing dopamine transporter (DAT) functioning via genetic (knockdown vs. wild-type littermates), or pharmacological (GBR12909- vs. vehicle-treated C57BL/6J mice) means were assessed in the probabilistic reversal learning task (PRLT), and progressive ratio breakpoint (PRB) test, during either water or chronic lithium treatment. These tasks quantify reward learning and effortful motivation, respectively. Neurochemistry was performed on brain samples of DAT mutants ± chronic lithium using high performance liquid chromatography. RESULTS: Reduced DAT functioning increased reversals in the PRLT, an effect partially attenuated by chronic lithium. Chronic lithium alone slowed PRLT acquisition. Reduced DAT functioning increased motivation (PRB), an effect attenuated by lithium in GBR12909-treated mice. Neurochemical analyses revealed that DAT knockdown mice exhibited elevated homovanillic acid levels, but that lithium had no effect on these elevated levels. CONCLUSIONS: Reducing DAT functioning recreates many aspects of BD mania including hypermotivation and improved reversal learning (switching), as well as elevated homovanillic acid levels. Chronic lithium only exerted main effects, impairing learning and elevating norepinephrine and serotonin levels of mice, not specifically treating the underlying mechanisms identified in these models.
Subject(s)
Bipolar Disorder/metabolism , Brain Chemistry/physiology , Dopamine Plasma Membrane Transport Proteins/physiology , Lithium/administration & dosage , Motivation/physiology , Problem Solving/physiology , Animals , Bipolar Disorder/psychology , Brain Chemistry/drug effects , Conditioning, Operant/drug effects , Conditioning, Operant/physiology , Disease Models, Animal , Drug Administration Schedule , Homovanillic Acid/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Motivation/drug effects , Problem Solving/drug effectsABSTRACT
Developing methods for improving creativity is of broad interest. Classic psychedelics may enhance creativity; however, the underlying mechanisms of action are unknown. This study was designed to assess whether a relationship exists between naturalistic classic psychedelic use and heightened creative problem-solving ability and if so, whether this is mediated by lifetime mystical experience. Participants (N = 68) completed a survey battery assessing lifetime mystical experience and circumstances surrounding the most memorable experience. They were then administered a functional fixedness task in which faster completion times indicate greater creative problem-solving ability. Participants reporting classic psychedelic use concurrent with mystical experience (n = 11) exhibited significantly faster times on the functional fixedness task (Cohen's d = -.87; large effect) and significantly greater lifetime mystical experience (Cohen's d = .93; large effect) than participants not reporting classic psychedelic use concurrent with mystical experience. However, lifetime mystical experience was unrelated to completion times on the functional fixedness task (standardized ß = -.06), and was therefore not a significant mediator. Classic psychedelic use may increase creativity independent of its effects on mystical experience. Maximizing the likelihood of mystical experience may need not be a goal of psychedelic interventions designed to boost creativity.
Subject(s)
Hallucinogens/pharmacology , Mysticism/psychology , Problem Solving/drug effects , Substance-Related Disorders/psychology , Adolescent , Adult , Creativity , Female , Hallucinogens/administration & dosage , Humans , Male , Surveys and Questionnaires , Young AdultABSTRACT
Adverse environmental factors including prenatal maternal infection are capable of inducing long-lasting behavioral and neural alterations which can enhance the risk to develop schizophrenia. It is so far not clear whether supportive postnatal environments are able to modify such prenatally-induced alterations. In rodent models, environmental enrichment influences behavior and cognition, for instance by affecting endocrinologic, immunologic, and neuroplastic parameters. The current study was designed to elucidate the influence of postnatal environmental enrichment on schizophrenia-like behavioral alterations induced by prenatal polyI:C immune stimulation at gestational day 9 in mice. Adult offspring were tested for amphetamine-induced locomotion, social interaction, and problem-solving behavior as well as expression of dopamine D1 and D2 receptors and associated molecules, microglia density and adult neurogenesis. Prenatal polyI:C treatment resulted in increased dopamine sensitivity and dopamine D2 receptor expression in adult offspring which was not reversed by environmental enrichment. Prenatal immune activation prevented the effects of environmental enrichment which increased exploratory behavior and microglia density in NaCl treated mice. Problem-solving behavior as well as the number of immature neurons was affected by neither prenatal immune stimulation nor postnatal environmental enrichment. The behavioral and neural alterations that persist into adulthood could not generally be modified by environmental enrichment. This might be due to early neurodevelopmental disturbances which could not be rescued or compensated for at a later developmental stage.