Serotonin and human cognitive performance Schmitt, J A J; Wingen, M; Ramaekers, J G ...
Current pharmaceutical design,
07/2006, Letnik:
12, Številka:
20
Journal Article
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In the past decade, experimental studies involving healthy human volunteers have revealed that manipulations of the central serotonin (5-HT) system can produce quite specific changes in cognitive ...functioning, independent of overt mood changes. Reduced 5-HT turnover is consistently associated with impaired long-term memory functioning. Low 5-HT function may also impair cognitive flexibility and improve focused attention. On the other hand, stimulation of central 5-HT has repeatedly been found to impair performance in a true vigilance task. Currently, there is little evidence for mirrored cognitive changes due to opposite 5-HT manipulations in healthy volunteers. Given the mounting evidence for a role of 5-HT in human cognition, reduced 5-HT function could be directly linked to cognitive disturbances in certain conditions, such as in depression and Alzheimer's Disease (AD). There is evidence that stimulating (i.e. normalizing) 5-HT activity in depression may have specific beneficial effects on cognition, independent of a general relief of depressive symptoms, but this premise needs to be confirmed by larger-scale clinical studies. Recently, a potential role of 5-HT in the cognitive symptoms in AD has been identified, but there is insufficient data to evaluate the effects of 5-HT stimulation on cognitive symptoms in AD. It is concluded that serotonin is a potential target for pharmacological cognition enhancement, particularly for restoration of impaired cognitive performance due to 5-HT dysfunction. Further differentiation of the role of 5-HT in normal and disturbed cognition and evaluation of the effects of 5-HT manipulations in various populations is required to establish the full potential of 5-HT drugs as cognition enhancers.
Alterations in serotonin signalling within the brain-gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) ...decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD.
12 healthy females (19-25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24-50 years).
In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C.
The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced visceral hyperalgesia in healthy controls, and the near-identical effective connectivity pattern observed in patients with IBS-C, these findings suggest that dysregulation of this brain network may play a role in central pain amplification and IBS pathophysiology.
Microbial survival of heating and cross-contamination are the two transmission routes during food preparation in the consumers' kitchen that are relevant for QMRA (Quantitative Microbial Risk ...Assessment). The aim of the present study was to extend the limited amount of data on microbial survival during real-life preparation of meat and meat products and to obtain accessory temperature data that allow for a more general (product unspecific) approach. Therefore survival data were combined with extensive measurements of time- and location dependent temperature using an infrared camera for the surface and buttons for the inside of the product, supplemented with interpolation modelling. We investigated the survival of heating of Escherichia coli O111:H2 in beefsteak, hamburgers (beef and 50% beef 50% pork (HH)), meatballs (beef and HH) and crumbs (HH).
For beefsteak, survival as a whole is dominated by the sides, giving a log reduction of 1–2 (rare), 3–4 (medium) and 6–7 (done). Limited measurements indicated that done preparation gave 5–6 log reduction for crumbs and at least 8–9 log for the other products. Medium preparation gave a higher reduction in hamburgers (2–4 log) than in meatballs (1–2 log) and in beef (3–4) than in HH (2–3) hamburgers. In general, our ‘done’ results give larger inactivation than found in literature, whereas ‘rare’ and ‘medium’ results are similar.
The experiments resulted in two types of curves of D70/z-values, dependent on product, doneness and for beefsteaks sides vs. top/bottom. One type of curve agrees reasonably with literature D70/z estimates from isothermal temperature experiments, which supports using these estimates for home style cooking QMRA calculations. In case of the other type of curve, which is mainly found for (near) surface contamination in close contact with the pan, these literature estimates cannot be applied.
We also applied a simplified approach, assuming thermal inactivation is dominated by the highest temperatures reached. The time duration of this highest temperature gives accessory D-values which prove to fit with isothermal temperature literature data, thus suggesting application of such data for QMRA is possible by this approach also, which is less labor intensive both in terms of measurements and modelling.
In real life, variability in product properties and preparation styles is large. Further studies are needed to analyze the effect on survival, preferably focusing on determining the essential variables. More variation in heating time will allow for estimating D70/z point estimates rather than curves representing possible sets of D70/z-values.
•Survival of E. coli and temperature of meat were studied at home frying conditions.•We studied beefsteak, hamburgers, meat balls and crumbs.•Inactivation was from 1 to 2 log (rare beefsteak) to at least 8–9 log (done products).•Results from D/z- and simplified analysis partly agree with isothermal literature.•Isothermal data can therefore support the estimation of survival after home frying.
Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by central hypoventilation, leading to the majority of patients being dependent on ventilatory support during ...sleep. This condition is often accompanied by various associated symptoms, due to a PHOX2B gene variant involved in neuronal crest cell migration. This study is the first to review the characteristics and outcomes in children with CCHS on long-term mechanical ventilation in the Netherlands. We performed a retrospective study of all CCHS patients treated in the 4 Centers of Home Mechanical Ventilation of the University Medical Centers in the Netherlands from 2000 till 2022 by collecting information from the electronic medical records, documented during follow-up. We included 31 patients, out of which 27 exhibited a known genetic profile associated with CCHS, while no PHOX2B variant was identified in the remaining patients. Among the 27 patients with known genetic profiles, 10 patients had a non-polyalanine repeat expansion mutation (NPARM), followed by 20/27, 20/25, and 20/26 polyalanine repeat expansion mutations (PARMs) in descending order. The most common presentation involved respiratory failure or apneas during the neonatal period with an inability to wean off ventilation. The majority of patients required ventilatory support during sleep, with four patients experiencing life-threatening events related to this dependency. Daily use of ventilatory support varied among different genetic profiles. All genotypes reported comorbidities, with Hirschsprung’s disease and cardiac arrhythmias being the most reported comorbidities. Notably, Hirschprung’s disease was exclusively observed in patients with a 20/27 PHOX2B variant.
Conclusion
: Our study results suggest that in our cohort, the genotype is not easily associated to the phenotype in CCHS. Consistent with these findings and international literature, we recommend a thorough annual evaluation for all patients with CCHS to ensure optimal management and follow-up.
What is Known:
• The majority of CCHS patients are dependent on ventilatory support.
• Variants in the PHOX2B gene are responsible for the characteristics of CCHS.
What is New:
• This study provides insight into the clinical course and long-term outcomes of CCHS patients in the Netherlands.
• In CCHS, the genotype is not easily associated with the phenotype, requiring a thorough life-long follow-up for all patients.
Dopamine plays an important role in goal-directed behavior, through its modulatory influence on striatal neurons. It is unclear whether tonic dopamine levels, which regulate the vigor of acting, ...interact with the phasic dopamine response to reward that drives instrumental behavior. In a randomized placebo-controlled study in healthy volunteers, we show that methylphenidate, a drug that increases tonic dopamine levels, systematically reduced striatal phasic BOLD responses to gain and loss in a gambling task as measured with fMRI. It also increased response vigor and reward expectancy-related BOLD signals in the ventral striatum. These findings suggest that striatal tonic dopamine levels constitute an average reward expectation signal that modulates the phasic dopaminergic response to reward. This offers opportunities for treatment of behavioral disorders associated with abnormal reward sensitivity.
Abstract
The coherent electron spin dynamics of an ensemble of singly charged (In,Ga)As/GaAs quantum dots in a transverse magnetic field is driven by periodic optical excitation at 1 GHz repetition ...frequency. Despite the strong inhomogeneity of the electron
g
factor, the spectral spread of optical transitions, and the broad distribution of nuclear spin fluctuations, we are able to push the whole ensemble of excited spins into a single Larmor precession mode that is commensurate with the laser repetition frequency. Furthermore, we demonstrate that an optical detuning of the pump pulses from the probed optical transitions induces a directed dynamic nuclear polarization and leads to a discretization of the total magnetic field acting on the electron ensemble. Finally, we show that the highly periodic optical excitation can be used as universal tool for strongly reducing the nuclear spin fluctuations and preparation of a robust nuclear environment for subsequent manipulation of the electron spins, also at varying operation frequencies.
Cognitive flexibility is the ability to adjust behavior to changes in the environment or task conditions. Previous research suggested that serotonin (5-HT) is involved in cognitive flexibility. ...Disturbed 5-HT functioning in animals, psychiatric patients and healthy volunteers leads to more rigid behavior. A well recognized method to manipulate levels of brain 5-HT is acute tryptophan depletion (ATD). This method induces a transient and reversible lowering of plasma tryptophan that has been shown to result in decreased brain 5-HT. Only recently has ATD research been combined with functional Magnetic Resonance Imaging (fMRI). In this review, we discuss recent investigations into the effect of ATD on the Blood Oxygen Level Dependent (BOLD) response during tasks that require cognitive flexibility, in healthy volunteers. Functional MRI studies have shown that ATD changes brain activation during tasks that require cognitive flexibility. It is hypothesized that ATD changes the processing of negative feedback, rather than impairing response inhibition, impairing the response to an error or the loss of cognitive control during response interference. Although the results of these studies are intriguing, they are sometimes contradictory. This could be the result of the different paradigms that have been used. Importantly, these studies strongly suggest that future multidisciplinary research should evaluate the mechanisms underlying individual differences and control for variables that have been shown to interact with the effect of ATD on cognitive flexibility and the related brain activation.
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