Serotonergic modulation of cognition; An acute challenge

2017 ◽  
Vol 41 (S1) ◽  
pp. S350-S350
Author(s):  
N. Skandali ◽  
J. Rowe ◽  
J. Deakin ◽  
T. Robbins ◽  
B. Sahakian

AbstractSerotonin is well known to affect the multifaceted construct of impulsivity. Lowering brain serotonin levels is shown to increase impulsive choice in delay-discounting tasks (1) but improves response inhibition in stop-signal paradigms. (2) Administration of the antidepressant citalopram in healthy people increases tendency to perform go choices in a Go/No-Go task independent of outcome valence (3). It is rather unclear thought how serotonergic neurotransmission affects several aspects of cognition. We administered a single dose of 20 mg escitalopram, a selective serotonin reuptake inhibitor, to 66 healthy participants, aged 18–45 years old, in a double-blind, randomized, placebo-controlled, parallel-groups study. Acute escitalopram administration had a beneficial effect on inhibitory control with reduced stop-signal reaction time observed in the treatment group. Participants made significantly more errors in a probabilistic learning task and had lower accuracy during the discrimination stage in an instrumental learning task thus indicating a learning impairment. More errors in the CANTAB intra-extra dimensional set shift task were also observed in the escitalopram-treated group. Our findings following acute administration of a clinically relevant dose of escitalopram show a dissociate role for serotonin in modulating cognition mediated by a potentially differential modulation of fronto-striatal loops.Disclosure of interestThe authors have not supplied their declaration of competing interest.

2020 ◽  
Author(s):  
Zsolt Turi ◽  
Matthias Mittner ◽  
Albert Lehr ◽  
Hannah Bürger ◽  
Andrea Antal ◽  
...  

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.


Author(s):  
Dora Matzke ◽  
Conor V. Dolan ◽  
Gordon D. Logan ◽  
Scott D. Brown ◽  
Eric-Jan Wagenmakers

1974 ◽  
Vol 32 (02/03) ◽  
pp. 468-482 ◽  
Author(s):  
O Storm ◽  
P Ollendorff ◽  
E Drewsen ◽  
P Tang

SummaryThe thrombolytic effect of pig plasmin was tested in a double blind trial on patients with deep venous thrombosis in the lower limb. Only patients with not more than three days old thrombi were selected for this study. The diagnosis of deep vein thrombosis was made clinically and confirmed by phlebography. Lysofibrin Novo (porcine plasmin) or placebo (porcine plasminogen) was administered intravenously to the patients. The enzyme and the placebo were delivered as lyophilized powder in labelled bottles - the contents of the bottles were unknown to the doctor in charge of the clinical administration of the trial. An initial dose of plasmin/plasminogen of 30 unit per kg body weight given slowly intravenously (1-1% hours infusion) was followed by a maintenance dosis of 15 per cent the initial dose per hour for the following 5-7 hours. In most cases a similar maintenance dosis was given the next day. In all patients heparin was administered after ending the plasmin/plasminogen infusion. The results of the treatment was evaluated clinically as well as by control phlebo- grams the following days.A statistically significant improvement was found in the plasmin treated group compared with the placebo (plasminogen) treated group. Thrombolysis was obtained clinically and phlebographically in 65 per cent of the plasmin treated group, but only in 15 per cent of the control patients were improvements found.This study has thus demonstrated that plasmin treatment according to a standard scheme was able to induce thrombolysis. There were only a few and insignificant side effects. Allergic reactions have not been seen and only very simple tests are required.


2021 ◽  
Vol 11 (4) ◽  
pp. 461
Author(s):  
Francesca Morreale ◽  
Zinovia Kefalopoulou ◽  
Ludvic Zrinzo ◽  
Patricia Limousin ◽  
Eileen Joyce ◽  
...  

As part of the first randomized double-blind trial of deep brain stimulation (DBS) of the globus pallidus (GPi) in Tourette syndrome, we examined the effect of stimulation on response initiation and inhibition. A total of 14 patients with severe Tourette syndrome were recruited and tested on the stop signal task prior to and after GPi-DBS surgery and compared to eight age-matched healthy controls. Tics were significantly improved following GPi-DBS. The main measure of reactive inhibition, the stop signal reaction time did not change from before to after surgery and did not differ from that of healthy controls either before or after GPi-DBS surgery. This suggests that patients with Tourette syndrome have normal reactive inhibition which is not significantly altered by GPi-DBS.


Author(s):  
Martina Montalti ◽  
Marta Calbi ◽  
Valentina Cuccio ◽  
Maria Alessandra Umiltà ◽  
Vittorio Gallese

AbstractIn the last decades, the embodied approach to cognition and language gained momentum in the scientific debate, leading to evidence in different aspects of language processing. However, while the bodily grounding of concrete concepts seems to be relatively not controversial, abstract aspects, like the negation logical operator, are still today one of the main challenges for this research paradigm. In this framework, the present study has a twofold aim: (1) to assess whether mechanisms for motor inhibition underpin the processing of sentential negation, thus, providing evidence for a bodily grounding of this logic operator, (2) to determine whether the Stop-Signal Task, which has been used to investigate motor inhibition, could represent a good tool to explore this issue. Twenty-three participants were recruited in this experiment. Ten hand-action-related sentences, both in affirmative and negative polarity, were presented on a screen. Participants were instructed to respond as quickly and accurately as possible to the direction of the Go Stimulus (an arrow) and to withhold their response when they heard a sound following the arrow. This paradigm allows estimating the Stop Signal Reaction Time (SSRT), a covert reaction time underlying the inhibitory process. Our results show that the SSRT measured after reading negative sentences are longer than after reading affirmative ones, highlighting the recruitment of inhibitory mechanisms while processing negative sentences. Furthermore, our methodological considerations suggest that the Stop-Signal Task is a good paradigm to assess motor inhibition’s role in the processing of sentence negation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mario Paci ◽  
Giulio Di Cosmo ◽  
Mauro Gianni Perrucci ◽  
Francesca Ferri ◽  
Marcello Costantini

AbstractInhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to regulate impulses and responses. This ability can be measured via the Stop Signal Task, which provides a temporal index of response inhibition, namely the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) allows to investigate motor inhibition within the primary motor cortex (M1), such as the cortical silent period (CSP) which is an index of GABAB-mediated intracortical inhibition within M1. Although there is strong evidence that intracortical inhibition varies during action stopping, it is still not clear whether differences in the neurophysiological markers of intracortical inhibition contribute to behavioral differences in actual inhibitory capacities. Hence, here we explored the relationship between intracortical inhibition within M1 and behavioral response inhibition. GABABergic-mediated inhibition in M1 was determined by the duration of CSP, while behavioral inhibition was assessed by the SSRT. We found a significant positive correlation between CSP’s duration and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition seem to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities.


BJPsych Open ◽  
2020 ◽  
Vol 6 (6) ◽  
Author(s):  
Catherine Hobbs ◽  
Susannah E. Murphy ◽  
Lucy Wright ◽  
James Carson ◽  
Indra Van Assche ◽  
...  

Background Depression is characterised by negative views of the self. Antidepressant treatment may remediate negative self-schema through increasing processing of positive information about the self. Changes in affective processing during social interactions may increase expression of prosocial behaviours, improving interpersonal communications. Aims To examine whether acute administration of citalopram is associated with an increase in positive affective learning biases about the self and prosocial behaviour. Method Healthy volunteers (n = 41) were randomised to either an acute 20 mg dose of citalopram or matched placebo in a between-subjects double-blind design. Participants completed computer-based cognitive tasks designed to measure referential affective processing, social cognition and expression of prosocial behaviours. Results Participants administered citalopram made more cooperative choices than those administered placebo in a prisoner's dilemma task (β = 20%, 95% CI: 2%, 37%). Exploratory analyses indicated that participants administered citalopram showed a positive bias when learning social evaluations about a friend (β = 4.06, 95% CI: 0.88, 7.24), but not about the self or a stranger. Similarly, exploratory analyses found evidence of increased recall of positive words and reduced recall of negative words about others (β = 2.41, 95% CI: 0.89, 3.93), but not the self, in the citalopram group. Conclusions Participants administered citalopram showed greater prosocial behaviours, increased positive recall and increased positive learning of social evaluations towards others. The increase in positive affective bias and prosocial behaviours towards others may, at least partially, be a mechanism of antidepressant effect. However, we found no evidence that citalopram influenced self-referential processing.


1997 ◽  
Vol 25 (4) ◽  
pp. 358-364
Author(s):  
W. Rushatamukayanunt ◽  
T. Tritrakarn

A comparison between midazolam and midazolam-flumazenil for total intravenous anaesthesia in combination with topical anaesthesia and muscle relaxants was performed in a double-blind, parallel study in 40 patients scheduled for microlaryngoscopy with or without bronchoscopic procedures using jet ventilation with oxygen. A single intravenous injection of midazolam 0.3 mg/kg, lignocaine spray and muscle relaxants provided adequate anaesthesia and good operative conditions throughout the procedures, which took 20 to 30 minutes. Patients who had placebo at the end of the procedures had a longer recovery and a high incidence of airway obstruction (20%). Administration of flumazenil provided prompt awakening in 19 of 20 patients (95%) within five minutes, resulting in rapid and favourable recovery without resedation or other side-effects, while only three of 20 (15%) patients in the placebo-treated group had improved consciousness within five minutes. The simplicity and reliability of the midazolam-flumazenil technique is attractive. We consider it worthy of further investigation for wider application in clinical practice.


CNS Spectrums ◽  
2006 ◽  
Vol 11 (12) ◽  
pp. 956-965 ◽  
Author(s):  
Stefano Pallanti ◽  
Silvia Bernardi ◽  
Leonardo Quercioli ◽  
Concetta DeCaria ◽  
Eric Hollander

ABSTRACTObjectiveAcute administration of the partial serotonin (5-HT) agonist meta-chlorophenylpi-perazine (m-CPP), that is used also as a street drug, has been reported to induce a “high” and craving response in various impulsive and sub-stance addiction disorders.IntroductionTo clarify altered 5-HT metabolism in pathological gamblers and to explore the specific role of serotonergic system in non substance addictions, we assessed behavioral (“high” and “craving”) and neuroendocrine (prolactin and cortisol) responses to an oral single dose of m-CPP and placebo in pathological gamblers and matched controls. Moreover, the relationship between neuroendocrine outcome and clinical severity has been assessed.MethodTwenty-six pathological gamblers and 26 healthy control subjects enter a double-blind, placebo-controlled-crossed administration of orally dose m-CPP 0.5 mg/kg. Outcome measures included prolactin and cortisol levels, gambling severity, mood, craving and “high” scales.ResultsPathological gamblers had significantly increased prolactin response compared to controls at 180 minutes and at 210 minutes post–administration. Greater pathological gamblers severity correlated with increased neuroendocrine responsiveness to m-CCP, suggesting greater 5-HT dysregulation. Pathological gambling patients had a significantly increased “high” sensation after m-CPP administration compared with control.ConclusionThese results provide additional evidence for 5-HT disturbance in pathological gamblers and they support the hypotheses that the role of the 5-HT dysfunction related to the experience of “high” might represent the path-way that leads to dyscontrolled behavior in patho-logical gamblers. Furthermore, the “high” feeling induced by m-CPP in pathological subjects may represent a marker of vulnerability to both behav-ioral and substance addictions.


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