scholarly journals Dopamine D2 receptor stimulation modulates the balance between ignoring and updating according to baseline working memory ability

2019 ◽  
Vol 33 (10) ◽  
pp. 1254-1263 ◽  
Author(s):  
Sean James Fallon ◽  
Annika Kienast ◽  
Kinan Muhammed ◽  
Yuen-siang Ang ◽  
Sanjay G Manohar ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Control ◽  
Drug Administration ◽  
Dopamine D2 Receptor ◽  
Negative Relationship ◽  
Response Conflict ◽  
Controlled Study ◽  
Dopamine Synthesis ◽  
Receptor Stimulation ◽  
Double Blind

Background: Working memory (WM) deficits in neuropsychiatric disorders have often been attributed to altered dopaminergic signalling. Specifically, D2 receptor stimulation is thought to affect the ease with which items can be gated into and out of WM. In addition, this effect has been hypothesised to vary according to baseline WM ability, a putative index of dopamine synthesis levels. Moreover, whether D2 stimulation affects WM vicariously through modulating relatively WM-free cognitive control processes has not been explored. Aims: We examined the effect of administering a dopamine agonist on the ability to ignore or update information in WM. Method: A single dose of cabergoline (1 mg) was administered to healthy older adult humans in a within-subject, double-blind, placebo-controlled study. In addition, we obtained measures of baseline WM ability and relatively WM-free cognitive control (overcoming response conflict). Results: Consistent with predictions, baseline WM ability significantly modulated the effect that drug administration had on the proficiency of ignoring and updating. High-WM individuals were relatively better at ignoring compared to updating after drug administration. Whereas the opposite occurred in low-WM individuals. Although the ability to overcome response conflict was not affected by cabergoline, a negative relationship between the effect the drug had on response conflict performance and ignoring was observed. Thus, both response conflict and ignoring are coupled to dopaminergic stimulation levels. Conclusions: Cumulatively, these results provide evidence that dopamine affects subcomponents of cognitive control in a diverse, antagonistic fashion and that the direction of these effects is dependent upon baseline WM.

scholarly journals No evidence that LSD microdosing affects recall or the balance between distracter resistance and updating

2021 ◽  
Author(s):  
Sean James Fallon
Keyword(s):  
Working Memory ◽  
Computational Models ◽  
Small Sample ◽  
Controlled Study ◽  
Memory Recall ◽  
Or Efficiency ◽  
Double Blind ◽  
Match To Sample ◽  
States Of Consciousness ◽  
Dmts Task

AbstractThe effect of low doses (<=20 μg) of LSD on working memory, in the absence of altered states of consciousness, remain largely unexplored. Given its possible effects on serotonin 5-HT2A receptors and dopaminergic signalling, it could be hypothesised that LSD microdoses modulate working memory recall. Moreover, in line with computational models, LSD microdoses could exert antagonistic effects on distracter resistance and updating. Here, we tested this hypothesis in a randomised double-blind, placebo-controlled study comparing three different LSD microdoses (5 μg, 10μg and 20μg) with placebo. After capsule administration, participants performed a modified delay-match-to-sample (DMTS) dopamine-sensitive task. The standard DMTS task was modified to include novel items in the delay period between encoding and probe. These novel items either had to be ignored or updated into working memory. There was no evidence that LSD microdoses affected the accuracy or efficiency of working memory recall and there was no evidence for differential effects on ignoring or updating. Due to the small sample of participants, these results are preliminary and larger studies are required to establish whether LSD microdoses affect short-term recall.

scholarly journals Stress matters: a double-blind, randomized controlled trial on the effects of a multispecies probiotic on neurocognition

2018 ◽  
Author(s):  
Papalini S. ◽  
Michels F. ◽  
Kohn N. ◽  
Wegman J. ◽  
van Hemert S. ◽  
...  
Keyword(s):  
Working Memory ◽  
Emotion Regulation ◽  
Placebo Group ◽  
Cognitive Control ◽  
Digit Span ◽  
Self Report ◽  
List Type ◽  
Double Blind ◽  
Emotion Reactivity ◽  
Neurocognitive Measures

AbstractProbiotics are microorganisms that can provide health benefits when consumed. Recent animal studies have demonstrated that probiotics can reverse gut microbiome-related alterations in anxiety and depression-like symptoms, in hormonal responses to stress, and in cognition. However, in humans, the effects of probiotics on neurocognition remain poorly understood and a causal understanding of the gut-brain link in emotion and cognition is lacking. We aimed to fill this gap by studying the effects of a probiotics intervention versus placebo on neurocognition in healthy human volunteers.We set out to investigate the effects of a multispecies probiotic (Ecologic®Barrier) on specific neurocognitive measures of emotion reactivity, emotion regulation, and cognitive control using fMRI. Critically, we also tested whether the use of probiotics can buffer against the detrimental effects of acute stress on working memory. In a double blind, randomized, placebo-controlled, between-subjects intervention study, 58 healthy participants were tested twice, once before and once after 28 days of intervention with probiotics or placebo.Probiotics versus placebo did not affect emotion reactivity, emotion regulation, and cognitive control processes at brain or behavioral level, neither related self-report measures. However, relative to the placebo group, the probiotics group did show a significant stress-related increase in working memory performance after versus before supplementation (digit span backward, p=0.039, ηp2=.07). Interestingly, this change was associated with intervention-related neural changes in frontal cortex during cognitive control in the probiotics group, but not in the placebo group. Overall, our results show that neurocognitive effects of supplementation with a multispecies probiotic in healthy women become visible under challenging (stress) situations. Probiotics buffered against the detrimental effects of stress in terms of cognition, especially in those individuals with probiotics-induced changes in frontal brain regions during cognitive control.HighlightsWe ran a randomized placebo-controlled fMRI study with a multispecies probioticProbiotics did not affect neurocognitive measures of emotion and cognitive controlProbiotics did affect stress-related working memory and neural correlatesProbiotics in healthy individuals can support cognition under stress

scholarly journals Safety and Effectiveness of SEP−363856 in Schizophrenia: Results of a 6-Month, Open-Label Extension Study

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 148-149
Author(s):  
Christoph U. Correll ◽  
Kenneth S. Koblan ◽  
Seth C. Hopkins ◽  
Justine Kent ◽  
Hailong Cheng ◽  
...  
Keyword(s):  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Receptor Occupancy ◽  
Term Treatment ◽  
Extension Study ◽  
Controlled Study ◽  
Minimal Risk ◽  
Symptom Scale ◽  
Open Label ◽  
Double Blind

AbstractBackgroundSEP-363856 is a novel psychotropic agent without dopamine D2 receptor occupancy. Although its mechanism of action has not been fully elucidated, preclinical data suggest that agonism at trace amine receptor 1 (TAAR1) and the serotonin 5-H1A receptor contributes to its efficacy. In a double-blind (DB), placebo-controlled study, SEP−363856 demonstrated significant efficacy in the treatment of an exacerbation of schizophrenia (Koblan et al, NEJM 2020; 82:1497–1506). We present results of a 6-month extension study whose aim was to evaluate the safety and effectiveness of longer-term treatment with SEP−363856.MethodPatients with an acute exacerbation of schizophrenia who completed a 4-week, DB, placebo-controlled, flexible-dose (50 or 75 mg) study of SEP−363856 were given the option to enroll in an extension study in which they were treated, open-label (OL), with flexible doses (25/50/75 mg/d) of SEP−363856 for 26-weeks. The primary outcomes were safety measures; effectiveness outcomes were secondary and included the PANSS total score and the Brief Negative Symptom Scale (BNSS) total score.ResultsA total of 193 patients completed the 4-week DB study, and 156 (80.8%) were dosed in the OL extension study and received at least one dose of SEP−363856 (safety population). Study completer rate was 66.9%; reasons for discontinuation consisted of adverse event (11.5%), withdrawal of consent (10.2%), lack of efficacy (5.1%), and other (6.4%). 15 patients experienced an SAE: schizophrenia (n=11); acute psychosis (N=1); uterine hemorrhage and suicidal ideation (N=1 each); there were no deaths in the study. Individual AEs with an incidence =2% were schizophrenia (12.2%), headache (11.5%), insomnia (8.3%), anxiety (5.1%), somnolence (4.5%), nasopharyngitis (4.5%), nausea (3.8%), irritability (3.2%), influenza (3.2%), weight decreased (3.2%), and prolactin increased (2.6%). On movement scales, minimal mean change from OL-baseline to Week 26 occurred on the Barnes total score (−0.1), AIMS total score (0.0) and SAS score (−0.1). Mean month 6 change from DB baseline in weight was −0.3 kg. No clinically meaningful median changes were observed at week 26 in metabolic laboratory parameters (total and LDL cholesterol, triglycerides, hemoglobin A1c) or in prolactin levels. During 6 months of OL treatment, one patient had an increase in QTcF =60 msec; no patients had a QTcF interval =480 msec. Treatment with SEP−363856 was associated with significant improvement from OL baseline to week 26 in PANSS total score (−22.6) and BNSS total score (−11.3).ConclusionTreatment with SEP−363856 was associated with continued improvement from open-label baseline in the PANSS total (−22.6) and BNSS total (−11.3) scores. The most frequently reported adverse events (= 5%) were schizophrenia, headache, insomnia and anxiety. SEP−363856 had minimal effects on weight, lipids, glycemic indices, prolactin, and was associated with minimal risk of extrapyramidal symptom.FundingSunovion Pharmaceuticals Inc.

scholarly journals The Acute and Chronic Cognitive Effects of a Sage Extract: A Randomized, Placebo Controlled Study in Healthy Humans

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 218
Author(s):  
Emma L. Wightman ◽  
Philippa A. Jackson ◽  
Bethany Spittlehouse ◽  
Thomas Heffernan ◽  
Damien Guillemet ◽  
...  
Keyword(s):  
Working Memory ◽  
Brain Function ◽  
Cognitive Outcomes ◽  
Controlled Study ◽  
Post Dose ◽  
Double Blind ◽  
Healthy Humans ◽  
The Impact

The sage (Salvia) plant contains a host of terpenes and phenolics which interact with mechanisms pertinent to brain function and improve aspects of cognitive performance. However, previous studies in humans have looked at these phytochemicals in isolation and following acute consumption only. A preclinical in vivo study in rodents, however, has demonstrated improved cognitive outcomes following 2-week consumption of CogniviaTM, a proprietary extract of both Salvia officinalis polyphenols and Salvia lavandulaefolia terpenoids, suggesting that a combination of phytochemicals from sage might be more efficacious over a longer period of time. The current study investigated the impact of this sage combination on cognitive functions in humans with acute and chronic outcomes. Participants (n = 94, 25 M, 69 F, 30–60 years old) took part in this randomised, double-blind, placebo-controlled, parallel groups design where a comprehensive array of cognitions were assessed 120- and 240-min post-dose acutely and following 29-day supplementation with either 600 mg of the sage combination or placebo. A consistent, significant benefit of the sage combination was observed throughout working memory and accuracy task outcome measures (specifically on the Corsi Blocks, Numeric Working Memory, and Name to Face Recall tasks) both acutely (i.e., changes within day 1 and day 29) and chronically (i.e., changes between day 1 to day 29). These results fall slightly outside of those reported previously with single Salvia administration, and therefore, a follow-up study with the single and combined extracts is required to confirm how these effects differ within the same cohort.

Single Oral Dose Administration Of A Specific Thromboxane Synthetase Inhibitor To Normal Volunteers - A Double Blind Placebo Controlled Study

1981 ◽  
Author(s):  
V V Kakkar ◽  
J Westwick ◽  
J Zahavi ◽  
H Tyler
Keyword(s):  
Oral Dose ◽  
Drug Administration ◽  
Clinical Chemistry ◽  
Controlled Study ◽  
Central Research ◽  
Double Blind ◽  
Platelet Factor ◽  
Synthetase Inhibitor ◽  
Thromboxane Synthetase Inhibitor ◽  
Thromboxane Synthetase

A specific thromboxane synthetase inhibitor (UK-37248-01) is a new imidazole derivative synthesised by Pfizer Central Research. In vitro and animal experiments showed the compound to be a potent, selective and orally active one.Six healthy male volunteers received a single dose of 100mg of a specific thromboxane synthetase inhibitor or a matching placebo in a double blind cross-over study, there being a 2 week interval between treatments. Production of thromboxane B2 in serum was markedly reduced 1 hour after the drug administration, with about 50% inhibition still evident at 6 hours. The drug had no effect no circulating β-thromboglobulin and platelet factor 4 antigen levels, or on platelet aggregation to ADP or collagen, though release of 5HT was reduced. Increase in bleeding time (2-3 minutes) was recorded in 3 volunteers 1 hour after the drug administration.Chemical assay of the compound showed that up to 45% of the oral dose was excreted in the urine within 24 hours; 90% of this was excreted within the first 4 hours. Routine haematology and clinical chemistry tests repeated 24 hours and 4 days after dosing gave no indication of drug related toxicity.

scholarly journals Consequences Of Prefrontal TDCS On Inhibitory Control And Reactive Aggression

2020 ◽  
Author(s):  
Carmen Weidler ◽  
Ute Habel ◽  
Paul Wallheinke ◽  
Lisa Wagels ◽  
Lena Hofhansel ◽  
...  
Keyword(s):  
Cognitive Control ◽  
Aggressive Behavior ◽  
Risk Groups ◽  
Cortical Activation ◽  
Stop Signal Task ◽  
Controlled Study ◽  
Double Blind ◽  
Taylor Aggression Paradigm ◽  
Dorsolateral Prefrontal ◽  
The Right

Abstract Increased aggression and impulsivity represent a key component of several psychiatric disorders, including substance use disorder, which is often associated with deficient prefrontal brain activation. Thus, innovative tools to increase cognitive control are highly warranted. The current study investigates the potential of transcranial direct current stimulation (tDCS), a tool to modulate cortical activation, to increase cognitive control in individuals with a high potential for impulsive and aggressive behavior. In a double-blind, sham-controlled study, we applied anodal tDCS over the right dorsolateral prefrontal cortex in an all-male sample of alcohol dependent patients (AD), tobacco users (TU) and healthy controls (HC) who completed the Taylor Aggression Paradigm and Stop Signal Task twice. While there were no observable effects of tDCS in controls, results revealed altered aggressive behavior in AD following active stimulation. Specifically, these individuals did not show the standard increase in aggression over time seen in the other groups. Furthermore, improved response inhibition was found in AD and TU following active but not sham stimulation. Our study demonstrates that prefrontal tDCS improves our laboratory measure of impulse control in at-risk groups, illustrating the importance of sample characteristics such as nicotine intake and personality traits for understanding the effects of brain stimulation.

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