12 tDCS modulation of pavlovian bias under intermittent loss of control

2020 ◽  
Vol 91 (8) ◽  
pp. e12.3-e13
Author(s):  
Terezie Lekscha Sedlinská ◽  
Lara Bolte ◽  
Eirik Melsæter ◽  
Gábor Csifcsák ◽  
Matthias Mittner
Keyword(s):  
Repeated Measures ◽  
Learning Task ◽  
Loss Of Control ◽  
Learning From Experience ◽  
Double Blind ◽  
Healthy Humans ◽  
Cortical Responses ◽  
Human Functioning ◽  
The Face ◽  
Response Feedback

Objectives/AimsLearning from experience and making decisions based on integrated environmental feedback is crucial for human functioning and wellbeing. Difficulties in learning and decision-making have been found in several psychiatric conditions. Pavlovian bias, a tendency to approach reward and remain passive in the face of punishment, can be advantageous in some situations, while in others, it can lead to maladaptive decisions and needs to be overcome by cognitive control. It has been suggested that healthy humans rely more heavily on Pavlovian bias when instrumental control over environmental reinforcers is compromised. In our study, we were focusing on the influence of transcranial direct current stimulation (tDCS) on Pavlovian bias during and after an intermittent loss of control over rewards and losses.MethodsIn our pilot study, 19 adults underwent three blocks of an orthogonalized go-nogo reinforcement learning task. Blocks 1 and 3 had a response-feedback contingency of 70–30%, enabling learning via trial-and-error. In the second block, the outcome was independent of the participants’ responses (50%-50% contingency level). Cortical responses of all participants were recorded via EEG. Multi-electrode tDCS targeting the medial prefrontal cortex was administered in a randomised, double-blind placebo-controlled manner.ResultsWe conducted a repeated-measures ANOVA with ‘session’ (PRE x tDCS x POST), ‘valence’ (Win x Avoid) and ‘PB-congruency’ (Pavlovian bias congruent x incongruent) as within-factors, ‘group’ (Active stimulation x Sham) as the between- factor and ‘accuracy’ as the dependent variable. The interaction of ‘session’ and ‘PB- congruency’ with F(2,16)=2.62, p=0.09 were marginally significant, pointing towards slightly enhanced Pavlovian bias in the second block. However, the interaction of ‘session’, ‘PB-congruency’ and ‘group’ was not significant (F(2,16)=0.46, p=0.63). The evaluation of the feedback-related negativity (FRN) in the EEG revealed gradually increasing amplitudes in reward trials in the sham group, whereas we found a trend towards reduced FRN amplitude in the active group with F(2,13)=2.83, p=0.08.ConclusionsOur preliminary data show that a loss of control over feedbacks might increase the effect of Pavlovian bias on the choices of all participants. Although active tDCS seems to attenuate cortical responses during feedback evaluation, this effect is not accompanied by alterations in choice behaviour. Our data collection is still ongoing. The results from the full sample of 50 participants will be analysed by February 2020.

scholarly journals Theta-gamma cross-frequency transcranial alternating current stimulation over the trough impairs cognitive control

2020 ◽  
Author(s):  
Zsolt Turi ◽  
Matthias Mittner ◽  
Albert Lehr ◽  
Hannah Bürger ◽  
Andrea Antal ◽  
...  
Keyword(s):  
Cognitive Control ◽  
Repeated Measures ◽  
Instrumental Learning ◽  
Learning Task ◽  
Alternating Current ◽  
Double Blind ◽  
Bayesian Hierarchical ◽  
Theta Wave ◽  
Gamma Frequency ◽  
Transcranial Alternating Current Stimulation

Cognitive control is a hypothetical mental process, which underlies adaptive goal-directed decisions. Previous studies have linked cognitive control to electrophysiological fluctuations in the theta band and theta-gamma cross-frequency coupling (CFC) arising from the cingulate and frontal cortices. Yet, to date the behavioral consequences of different forms of theta-gamma CFC remain elusive. Here, we studied the behavioral effects of the theta-gamma CFC via transcranial alternating current stimulation (tACS) designed to stimulate the frontal and cingulate cortices. Using a double-blind, randomized, repeated measures study design, 24 healthy participants were subjected to three main, active CFC-tACS protocols: Short gamma frequency bursts (80 Hz) were coupled to an ongoing theta cycle (4 Hz) to coincide with either the peaks or the troughs of the theta wave. In a third condition, the amplitude of the gamma oscillation was modulated by the phase of a theta cycle. In the fourth, control protocol, gamma was continuously superimposed over the theta cycle, therefore lacking any phase-specificity in the CFC. During the 20-minute stimulations, the participants performed a Go/NoGo monetary reward- and punishment-based instrumental learning task. A Bayesian hierarchical logistic regression analysis revealed that CFC-tACS over peak had no effects on the behavioral performance, whereas CFC-tACS over trough and, to a lesser extent, amplitude-modulated tACS reduced performance in conflicting trials. Our results suggest that cognitive control depends on the phase-specificity of the theta-gamma CFC.

scholarly journals Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of δ-9-THC

2018 ◽  
Vol 48 (16) ◽  
pp. 2748-2756 ◽  
Author(s):  
Sagnik Bhattacharyya ◽  
Thomas Sainsbury ◽  
Paul Allen ◽  
Chiara Nosarti ◽  
Zerrin Atakan ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Verbal Learning ◽  
Learning Task ◽  
Psychotic Symptoms ◽  
Neural Basis ◽  
Experimental Conditions ◽  
Double Blind ◽  
Left Hippocampus ◽  
Leave One Out ◽  
Psychotomimetic Effects

AbstractBackgroundCannabis and its main psychoactive ingredient δ-9-tetrahydrocannibidiol (THC) can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experience these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.MethodsWe investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared with those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomized, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n = 14) following THC administration and those who did not (NP; n = 22).ResultsUnder placebo conditions, there was significantly greater engagement of the left hippocampus (p < 0.001) in the TP group compared with the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (Spearman's ρ = 0.44, p = 0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC.ConclusionsThese results suggest that altered hippocampal activation during verbal encoding may serve as a marker of sensitivity to the acute psychotomimetic effects of THC.

scholarly journals Influence of intranasal oxytocin on fear consolidation in healthy humans

2019 ◽  
Vol 32 (6) ◽  
pp. e100131 ◽  
Author(s):  
Elizabeth Hoge ◽  
Eric Bui ◽  
Peter Rosencrans ◽  
Scott Orr ◽  
Rachel Ross ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Repeated Measures ◽  
Skin Conductance Response ◽  
De Novo ◽  
Fear Learning ◽  
Drug Trials ◽  
Conditioning Procedure ◽  
Double Blind ◽  
Healthy Humans ◽  
Main Effects

BackgroundAlthough recent data in healthy humans suggestthat treatment with intranasal oxytocin (OT) may facilitate extinction recall,to date, little is known about the effects of OT on memory consolidationprocesses.AimTo examine the effect of intranasal administration of OT compared with placebo on memory consolidation blockade of a de novo fear memory in a classical 2-day fear conditioning procedure.ResultsThere were no significant differences between the OT and the placebo groups on the first two extinction trials (mean (SD)=0.01 (0.39) vs 0.15 (0.31), t=−1.092, p=0.28). Similarly, during early extinction, analysis of variance for repeated measures failed to show significant main effects of extinction trials: trials (F(4, 112)=1.58, p=0.18), drug (F(1, 112)=0.13, p=0.72) or drug × trials interaction (F(4, 112)=0.76, p=0.56).ConclusionOur results suggest that OT administered in a double-blind fashion immediately after fear conditioning does not significantly reduce consolidation of fear learning as measured by a differential skin conductance response tested at the beginning of extinction.

Normalization of mediotemporal and prefrontal activity, and mediotemporal-striatal connectivity, may underlie antipsychotic effects of cannabidiol in psychosis

2020 ◽  
pp. 1-11 ◽  
Author(s):  
Aisling O'Neill ◽  
Robin Wilson ◽  
Grace Blest-Hopley ◽  
Luciano Annibale ◽  
Marco Colizzi ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Repeated Measures ◽  
Block Design ◽  
Study Drug ◽  
Learning Task ◽  
Blood Oxygen Level Dependent ◽  
Antipsychotic Treatment ◽  
Blood Oxygen Level ◽  
Double Blind ◽  
Associate Learning

Abstract Background Recent evidence suggests that cannabidiol (CBD), a non-intoxicating ingredient present in cannabis extract, has an antipsychotic effect in people with established psychosis. However, the effect of CBD on the neurocognitive mechanisms underlying psychosis is unknown. Methods Patients with established psychosis on standard antipsychotic treatment were studied on separate days at least one week apart, to investigate the effects of a single dose of orally administered CBD (600 mg) compared to a matched placebo (PLB), using a double-blind, randomized, PLB-controlled, repeated-measures, within-subject cross-over design. Three hours after taking the study drug participants were scanned using a block design functional magnetic resonance imaging (fMRI) paradigm, while performing a verbal paired associate learning task. Fifteen psychosis patients completed both study days, 13 completed both scanning sessions. Nineteen healthy controls (HC) were also scanned using the same fMRI paradigm under identical conditions, but without any drug administration. Effects of CBD on brain activation measured using the blood oxygen level-dependent hemodynamic response fMRI signal were studied in the mediotemporal, prefrontal, and striatal regions of interest. Results Compared to HC, psychosis patients under PLB had altered prefrontal activation during verbal encoding, as well as altered mediotemporal and prefrontal activation and greater mediotemporal-striatal functional connectivity during verbal recall. CBD attenuated dysfunction in these regions such that activation under its influence was intermediate between the PLB condition and HC. CBD also attenuated hippocampal-striatal functional connectivity and caused trend-level symptom reduction in psychosis patients. Conclusions This suggests that normalization of mediotemporal and prefrontal dysfunction and mediotemporal-striatal functional connectivity may underlie the antipsychotic effects of CBD.

scholarly journals Evidence of a Redox-Dependent Regulation of Immune Responses to Exercise-Induced Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Alexandra Sakelliou ◽  
Ioannis G. Fatouros ◽  
Ioannis Athanailidis ◽  
Dimitrios Tsoukas ◽  
Athanasios Chatzinikolaou ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Immune Cell ◽  
Redox Status ◽  
Creatine Kinase Activity ◽  
Protein Carbonyls ◽  
Antioxidant Supplementation ◽  
Double Blind ◽  
Repeated Measures Design ◽  
Healthy Humans ◽  
Exercise Induced

We used thiol-based antioxidant supplementation (n-acetylcysteine, NAC) to determine whether immune mobilisation following skeletal muscle microtrauma induced by exercise is redox-sensitive in healthy humans. According to a two-trial, double-blind, crossover, repeated measures design, 10 young men received either placebo or NAC (20 mg/kg/day) immediately after a muscle-damaging exercise protocol (300 eccentric contractions) and for eight consecutive days. Blood sampling and performance assessments were performed before exercise, after exercise, and daily throughout recovery. NAC reduced the decline of reduced glutathione in erythrocytes and the increase of plasma protein carbonyls, serum TAC and erythrocyte oxidized glutathione, and TBARS and catalase activity during recovery thereby altering postexercise redox status. The rise of muscle damage and inflammatory markers (muscle strength, creatine kinase activity, CRP, proinflammatory cytokines, and adhesion molecules) was less pronounced in NAC during the first phase of recovery. The rise of leukocyte and neutrophil count was decreased by NAC after exercise. Results on immune cell subpopulations obtained by flow cytometry indicated that NAC ingestion reduced the exercise-induced rise of total macrophages, HLA+macrophages, and 11B+macrophages and abolished the exercise-induced upregulation of B lymphocytes. Natural killer cells declined only in PLA immediately after exercise. These results indicate that thiol-based antioxidant supplementation blunts immune cell mobilisation in response to exercise-induced inflammation suggesting that leukocyte mobilization may be under redox-dependent regulation.

Un/re/production of Old Age inThe Taking of Deborah Logan

Somatechnics ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. 178-194
Author(s):  
Agnieszka Kotwasińska
Keyword(s):  
Alzheimer’S Disease ◽  
Old Age ◽  
Horror Film ◽  
Close Reading ◽  
Loss Of Control ◽  
Found Footage ◽  
Progressive Loss ◽  
The Face ◽  
Female Embodiment ◽  
Main Protagonist

The article offers a re-examination of abjected femininity and old age through a close reading of The Taking of Deborah Logan (2015), a found footage horror movie centered on spectral possession. While to a large extent the movie replicates an infamous monstrous old woman trope, it also effectively questions typical Alzheimer's disease (AD) narratives, which tend to portray life with AD as a story of unmitigated loss and debility. In The Taking of Deborah Logan, potentially destabilizing moments occur when in the face of progressive loss of control, memory, and bodily functions, the main protagonist is momentarily experienced as resisting the dehumanisation and loss of agency conventionally associated with AD and possession alike. The aim of this article is thus three-fold. The first part sketches the processes through which possession narratives generate a highly ambivalent space for aging femininity in horror film, and how aging, disability, and AD intersect both in popular understanding and in film. In the second part, the author examines how The Taking of Deborah Logan, as a found footage horror, shapes a discussion about selfhood, agency, and monstrous embodiment. Finally, the author argues that it is through the concept of transaging that one can find ways to destabilise traditional understandings of old age, female embodiment, and AD, and offer new narratives that highlight monstrous, if ambivalent, agency.

scholarly journals Relative absorption of silicon from different formulations of dietary supplements: a pilot randomized, double-blind, crossover post-prandial study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
N. Boqué ◽  
R. M. Valls ◽  
A. Pedret ◽  
F. Puiggrós ◽  
L. Arola ◽  
...  
Keyword(s):  
Dietary Supplements ◽  
Inductively Coupled Plasma ◽  
Aloe Vera ◽  
Emission Spectrometry ◽  
Orthosilicic Acid ◽  
Post Dose ◽  
Double Blind ◽  
Gold Standard Method ◽  
Healthy Humans ◽  
Relative Absorption

AbstractThe purpose of the present study was to compare the relative absorption of a new powder presentation of silicon (Si) as orthosilicic acid with maltodextrin (Orgono Powder) compared to usual Si liquid presentations as orthosilicic acid with Equisetum arvense and Rosmarinus officinalis (G5 Siliplant) and orthosilicic acid with aloe vera (G7 Aloe). All dietary supplements were administered at the same Si oral dose (21.6 mg) in a randomized, double-blind, crossover post-prandial study conducted in 5 healthy men. Urine was collected at baseline and over the 6-h post-dose period in 2 separate 3-h collections for the analysis of Si concentration, which was conducted by inductively coupled plasma optical emission spectrometry as the gold standard method. No significant differences in total urinary Si excretion were found after the intake of these 3 dietary supplements; 34.6%, 32.4% and 27.2% of the ingested Si from G7 Aloe, G5 Siliplant and Orgono Powder, respectively, was excreted in urine over the 6-h follow-up period. The 3 different oral Si formulations tested, in powder and liquid presentations, provide highly bioavailable Si and present an equivalent relative absorption in healthy humans.

scholarly journals Efficacy of galcanezumab in patients with migraine who did not benefit from commonly prescribed preventive treatments

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dulanji K. Kuruppu ◽  
Joshua Tobin ◽  
Yan Dong ◽  
Sheena K. Aurora ◽  
Laura Yunes-Medina ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Migraine Headache ◽  
Mixed Model ◽  
Preventive Treatment ◽  
Response Rates ◽  
Toxin A ◽  
Double Blind ◽  
Preventive Medication ◽  
Onabotulinum Toxin A ◽  
Post Hoc

Abstract Background Galcanezumab is a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) indicated for the preventive treatment of migraine. While galcanezumab has demonstrated efficacy in patients who did not respond to prior preventive medications in general, its efficacy in patients who did not benefit from individual, commonly prescribed preventive treatments due to inadequate efficacy or safety/tolerability remains unknown. Methods CONQUER was a 3-month, randomized, double-blind, placebo-controlled, phase 3b study that enrolled patients with episodic or chronic migraine who had 2 to 4 migraine preventive medication category failures in the past 10 years. Patients were randomly assigned 1:1 to receive placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). Post hoc analyses were conducted to determine the efficacy of galcanezumab in patients who had not benefited from six of the most commonly prescribed migraine preventive medications. The mean change from baseline in monthly migraine headache days and ≥ 50 % response rates were assessed over months 1–3. Improvement in Migraine-Specific Questionnaire Role Function-Restrictive (MSQ-RFR) scores were assessed at month 3. The endpoints were estimated via mixed model with repeated measures. Results The most common treatment failures due to inadequate efficacy or safety/tolerability, which at least 20 % of patients reported trying without benefit, included topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and metoprolol. Patients who had not previously benefited from these treatments had a greater mean reduction in monthly migraine headache days across months 1–3 in the galcanezumab group compared to placebo (all p < 0.01). More patients treated with galcanezumab experienced a ≥ 50 % reduction from baseline in monthly migraine headache days across months 1–3 compared to placebo (all p < 0.05). Galcanezumab-treated patients had a greater improvement in mean MSQ-RFR scores at month 3 compared to placebo (all p < 0.01). Conclusions In this population, galcanezumab was effective in reducing monthly migraine headache days, improving response rates, and enhancing quality of life in patients who had not previously benefited from topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and/or metoprolol due to inadequate efficacy or safety/tolerability. Trial registration ClinicalTrials.gov NCT03559257 (CONQUER).

506 Samelisant: Baseline Characteristics from a Phase 2 Study Evaluating Efficacy and Safety in Patients with Narcolepsy

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A199-A199
Author(s):  
Ramakrishna Nirogi ◽  
Jyothsna Ravula ◽  
Pradeep Jayarajan ◽  
Satish Jetta ◽  
Gopinadh Bhyrapuneni ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Demographic Data ◽  
Fixed Ratio ◽  
Study Drug ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Healthy Humans ◽  
Parallel Group ◽  
Secondary Endpoints ◽  
Baseline Characteristics

Abstract Introduction histamine H3 receptor (H3R) antagonists/ inverse agonists increase histaminergic neurotransmission and offer a therapeutic option for the treatment of narcolepsy. Samelisant (SUVN-G3031) is a potent and selective H3R inverse agonist exhibited selectivity over 70 other targets. Samelisant showed wake-promoting and anticataplectic effects in orexin knockout mice suggesting its potential therapeutic utility in the treatment of EDS and cataplexy associated with narcolepsy. Safety and tolerability studies in animals and healthy humans suggested a favorable risk/benefit profile. Methods The current study is a 2 week treatment, multicenter, double-blind, placebo controlled, parallel-group study in patients with Narcolepsy with or without Cataplexy. Eligibility criteria include age between 18 to 50 years old, an ESS score of ≥ 12; and mean MWT time of &lt; 12 minutes and a confirm diagnosis of narcolepsy as per ICSD-3. Further, the randomization will be stratified according to type of narcolepsy (Type-1 or Type-2). Each subject will receive either placebo or study drug once daily for 2 weeks in a fixed ratio of 1:1:1. The primary efficacy endpoint is change in maintenance of wakefulness test (MWT) score from baseline to week 2. Key secondary endpoints include change from baseline to week 2 in ESS and an improvement in CGI-S scores. Safety will be monitored by medical monitor and by an independent data safety monitoring committee. Baseline clinical and demographic data for the currently enrolled study is summarized descriptively. Since the study is blinded, a breakdown of baseline characteristics by treatment group will not be available until after completion. Results As of data cutoff date of Dec 20, 2020, a total of 54 subjects were completed in the study. The median age of subjects was 30 years (range: 18 - 50 years) with mean BMI of 28.6 (range: 18.3 - 43.1 kg/m2). Overall, 74% of subjects were female and 83% were Caucasian. Mean (SD) baseline values of MWT and ESS are 5.65 (3.5) and 16.7 (2.5), respectively. Conclusion Baseline characteristics are consistent with the general narcolepsy population. The study is currently enrolling the subjects with Narcolepsy with or without Cataplexy, and the Data readout is expected in the second half of 2021. Support (if any):

scholarly journals Associative learning and extinction of conditioned threat predictors across sensory modalities

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Laura. R. Koenen ◽  
Robert. J. Pawlik ◽  
Adriane Icenhour ◽  
Ljubov Petrakova ◽  
Katarina Forkmann ◽  
...  
Keyword(s):  
Visceral Pain ◽  
Neural Correlates ◽  
Imaging Studies ◽  
Somatic Pain ◽  
Healthy Humans ◽  
Sensory Modalities ◽  
The Face ◽  
Nocebo Effects ◽  
Conditioned Responses ◽  
Clinical Conditions

AbstractThe formation and persistence of negative pain-related expectations by classical conditioning remain incompletely understood. We elucidated behavioural and neural correlates involved in the acquisition and extinction of negative expectations towards different threats across sensory modalities. In two complementary functional magnetic resonance imaging studies in healthy humans, differential conditioning paradigms combined interoceptive visceral pain with somatic pain (study 1) and aversive tone (study 2) as exteroceptive threats. Conditioned responses to interoceptive threat predictors were enhanced in both studies, consistently involving the insula and cingulate cortex. Interoceptive threats had a greater impact on extinction efficacy, resulting in disruption of ongoing extinction (study 1), and selective resurgence of interoceptive CS-US associations after complete extinction (study 2). In the face of multiple threats, we preferentially learn, store, and remember interoceptive danger signals. As key mediators of nocebo effects, conditioned responses may be particularly relevant to clinical conditions involving disturbed interoception and chronic visceral pain.

Sign in / Sign up

Export Citation Format

Share Document