Cognitive flexibility is a major requirement for successful goal-directed behavior and their neurobiological underpinnings are becoming better understood. However, the role of the norepinephrine system during task switching is largely enigmatic, despite neurobiological considerations make it likely that the norepinephrine system likely plays an important role. Theoretical considerations also suggest that the norepinephrine system mainly modulates task-switching processes when these rely upon working memory mechanisms. This topic was examined in the current system neurophysiological study integrating event-related potential (ERP) with pupil diameter data as a proximate the norepinephrine system activity. Combined with source localization methods, human brain structure, brain function, and phasic modulations by an important neurobiological system were integrated. The results show that cognitive-neurophysiological subprocesses during the actual switching processes, reflected by the N2 and P3 ERP components, are not modulated by the norepinephrine system. Rather, this system modulates preparatory processes in the fore period of stimuli signaling possible switches of response sets. The source localization results show that this is achieved by modulating neural processes in the temporo-parietal junction (BA40). Importantly, these phasic modulatory effects of the norepinephrine system were only evident when working memory processes had to be used to guide the selection of the appropriate responses for task switching.
- MeSH
- dospělí MeSH
- elektroencefalografie MeSH
- evokované potenciály fyziologie MeSH
- kognice fyziologie MeSH
- lidé MeSH
- mapování mozku * MeSH
- mladý dospělý MeSH
- noradrenalin fyziologie MeSH
- paměť fyziologie MeSH
- podněty MeSH
- pozornost fyziologie MeSH
- pupila MeSH
- reakční čas fyziologie MeSH
- temenní lalok fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The ability to execute several actions in a specific temporal order to achieve an overarching goal, a process often termed action cascading or multi-component behavior, is essential for everyday life requirements. We are only at the beginning to understand the neurobiological mechanisms important for these cognitive processes. However, it is likely that the locus coeruleus-norepinephrine (LC-NE) system may be of importance. In the current study we examine the relevance of the LC-NE system for action cascading processes using a system neurophysiological approach combining high-density EEG recordings and source localization to analyze event-related potentials (ERPs) with recordings of pupil diameter as a proximate of LC-NE system activity. N=25 healthy participants performed an action cascading stop-change paradigm. Integrating ERPs and pupil diameter using Pearson correlations, the results show that the LC-NE system is important for processes related to multi-component behavior. However, the LC-NE system does not seem to be important during the time period of response selection processes during multi-component behavior (reflected in the P3) as well as during perceptual and attentional selection (P1 and N1 ERPs). Rather, it seems that the neurophysiological processes in the fore period of a possibly upcoming imperative stimulus to initiate multi-component behavior are correlated with the LC-NE system. It seems that the LC-NE system facilitates responses to task-relevant processes and supports task-related decision and response selection processes by preparing cognitive control processes in case these are required during multi-component behavior rather than modulating these processes once they are operating.
- MeSH
- dospělí MeSH
- elektroencefalografie MeSH
- evokované potenciály MeSH
- exekutivní funkce fyziologie MeSH
- inhibice (psychologie) * MeSH
- lidé MeSH
- locus coeruleus fyziologie MeSH
- mladý dospělý MeSH
- noradrenalin fyziologie MeSH
- pozornost fyziologie MeSH
- psychomotorický výkon MeSH
- pupila fyziologie MeSH
- reakční čas MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Response inhibition processes are important for goal-directed behavior and particularly demanded when it is unlikely to inhibit automatically executed responses. It has been suggested that the norepinephrine (NE) system is important to consider for such likelihood effects. As an indirect measure of the NE system activity we used the pupil diameter and integrated this data with neurophysiological (EEG) data and beamforming analyses. The study shows that inhibitory control processes reflected by theta oscillations are strongly modulated by the likelihood to employ these processes and that these mechanisms were related to neural processes in the SMA and SFG. Probably, the modulations observed for theta band activity may reflect modulations in the encoding of a surprise, or conflict signal. Interestingly, correlation analyses of neuronal activity at the sensor and the source level with pupil diameter data revealed strong correlations that were only seen in the condition where inhibitory control processes were rarely demanded. On the basis of findings and theoretical models suggesting that the pupil diameter can be interpreted as a proximate of NE system activity the results may be interpreted that the NE system modulates inhibitory control processes via theta band activity in the SFB when the likelihood to inhibit a prepotent response tendency is low. From this it may be speculated that the NE system dynamically gains and loses relevance to modulate inhibitory control depending on boundary conditions that determine the mode of responding.
- MeSH
- dospělí MeSH
- elektroencefalografie metody MeSH
- evokované potenciály fyziologie MeSH
- exekutivní funkce fyziologie MeSH
- inhibice (psychologie) * MeSH
- lidé MeSH
- mladý dospělý MeSH
- noradrenalin fyziologie MeSH
- prefrontální mozková kůra fyziologie MeSH
- psychomotorický výkon fyziologie MeSH
- pupila fyziologie MeSH
- theta rytmus EEG fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Inhibitory control processes are a central executive function. Several lines of evidence suggest that the GABAergic and the norepinephrine (NE) system modulate inhibitory control processes. Yet, the effects of conjoint increases in the GABAergic and NE system activity on inhibitory control have not been examined. OBJECTIVE/HYPOTHESIS: We examine the conjoint effects of the GABA and NE system for inhibitory control. METHODS: We used transcutaneous vagus nerve stimulation (tVNS), which has been shown to modulate both the GABAergic and NE system. We examine the effects of tVNS in two experimental paradigms examining different aspect of inhibitory control; i.e. a backward inhibition paradigm and a response inhibition paradigm modulating working memory load. RESULTS: There were no effects of tVNS on backward inhibition processes, but on response inhibition processes. Yet, these only emerged when working memory processes were needed to control response inhibition. Compared to a sham stimulation, tVNS induced better response inhibition performance (i.e. fewer false alarms). CONCLUSIONS: A concomitant modulation of the GABAergic and NE system, as induced by tVNS, affects inhibitory control processes, but only when working memory processes play an important role for inhibitory control. Even though both the GABAergic and the NE system are modulated by tVNS, the results suggest that the modulation of the NE system is most important for the emerging effects.
- MeSH
- dospělí MeSH
- exekutivní funkce fyziologie MeSH
- GABA fyziologie MeSH
- inhibice (psychologie) * MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- noradrenalin fyziologie MeSH
- transkutánní elektrická neurostimulace metody MeSH
- vagová stimulace metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Sexuální dysfunkce jsou kvantitativními poruchami sexuální výkonnosti. Vyskytují se u jedinců obou pohlaví a jejich prevalence bývá udávána 15–40 %. Příčiny sexuálních dysfunkcí jsou velmi pestré, mohou mít organickou či psychogenní povahu a velmi často lze předpokládat multifaktoriální etiologii, tedy kombinaci organických, psychogenních a interpersonálních příčin. K narušení sexuálních funkcí však může dojít i při užívání některých léčiv. Sexuální dysfunkce jako nežádoucí účinek farmakoterapie jsou častým problémem např. při užívání některých antihypertenziv, antidepresiv, neuroleptik, antiepileptik, léčiv používaných v terapii benigní hyperplazie prostaty a mnoha dalších. Nežádoucí účinky léčiv na sexuální funkce se na první pohled mohou zdát nevýznamnými. Je však nutné si uvědomit, že sexuální život je v běžné populaci považován za velmi důležitou složku kvality života a sexuální dysfunkce navozené farmakoterapií mohou pacienty poměrně výrazně obtěžovat a mohou být zásadním důvodem jejich nonadherence k léčbě.
Sexual dysfunctions are quantitative disorders of sexual performance in both women and men, the prevalence is reported 15–40%. Causes of sexual dysfunctions are very varied, they can have organic or psychogenic character and in many cases we can expect multifactorial etiology, thus combination of organic, psychogenic and interpersonal causes. However, using of some drugs can lead to sexual dysfunctions. Sexual dysfunctions as adverse effect of pharmacotherapy are a frequent problem in the treatment with some antihypertensives, antidepressants, antipsychotics, antiepileptics, drugs for the treatment of benign prostatic hyperplasia and a lot of other drugs. Sexual adverse effects of pharmacotherapy seem to be unimportant at first glance. But it should be noted that sexuality is very important component of quality of life and sexual dysfunctions caused by pharmacotherapy can be inconveniencing and they can be the principal reason of medication nonadherence.
- MeSH
- acetylcholin fyziologie škodlivé účinky MeSH
- adherence k farmakoterapii MeSH
- dopamin fyziologie škodlivé účinky MeSH
- lidé MeSH
- noradrenalin fyziologie škodlivé účinky MeSH
- pohlavní steroidní hormony fyziologie škodlivé účinky MeSH
- prolaktin fyziologie škodlivé účinky MeSH
- serotonin fyziologie škodlivé účinky MeSH
- sexuální chování účinky léků MeSH
- sexuální dysfunkce fyziologická * etiologie chemicky indukované MeSH
- Check Tag
- lidé MeSH
Panická porucha je psychická porucha charakterizovaná rekurentními panickými atakami, které jsou doprovázeny výraznými somatickými a psychickými symptomy. Navzdory definovanému klinickému obrazu a ověřeným algoritmům léčby zůstává etiopatogeneze panické poruchy nejasná. Vzhledem k záchvatovému charakteru poruchy a symptomové rozmanitosti přinášejí funkční zobrazovací metody nejednoznačné výsledky. Nejlépe rozpracované jsou neurotransmiterové teorie opírající se o prokazatelnou úspěšnost antidepresiv. Tyto zahrnují roli řady neurotrasmiterů podílejících se na modulaci okruhu strachu (serotonin, noradrenalin, gamaaminomáselná kyselina, glutamát, kortikoliberin aj.). Z neuroanatomického hlediska se zdá pro spuštění panické ataky klíčová role centrálního jádra amygdaly, z nějž vystupuje velké množství drah zapojených do přípravy panické reakce. Oproti tomu protrahované úzkostné ladění je spojeno s aktivací lůžkového jádra striae terminalis. Celý proces je však komplexní a zahrnuje interakce jak s centry mozkového kmene, tak s vyššími centry kortikálními. Jejich role spočívá v modulaci afektivity limbického systému a jeho podřízení volním procesům.
Panic disorder is a mental disorder characterized by recurrent panic attacks accompanied by significant somatic and psychological symptoms. Ethiopathogenesis of panic disorder remains unclear although clinical manifestation and proven algorithms of treatment are known. Due to paroxysmal nature of the disorder and its symptoms, functional imaging techniques provide ambiguous results. Leading neurotransmitter theories are based on the proven efficacy of antidepressants treatment. This includes the role of the neurotransmitters involved in modulation of fear circuit (serotonin, norepinephrine, gamma-aminobutyric acid, glutamate, cortikoliberin etc.). From neuroanatomical point of view, the nucleus of amygdala, with a large number of pathways involved in the panic reaction, plays the key role in triggering panic attacks. In contrast, prolonged anxiety is associated with activation of bed nucleus striae terminalis. The entire process is complex and involves interaction of the brainstem and cortical centres, the role of which consists of affective modulation of the limbic system and its regulation by volitional processes. Key words: panic disorder – magnetic resonance imaging – positron emission tomography –serotonin – norepinephrine – amygdala –locus coeruleus – prefrontal lobes The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
- MeSH
- amygdala fyziologie patofyziologie MeSH
- lidé MeSH
- locus coeruleus fyziologie MeSH
- magnetická rezonanční tomografie MeSH
- modely neurologické * MeSH
- neurotransmiterové látky MeSH
- noradrenalin fyziologie MeSH
- panická porucha * etiologie patofyziologie MeSH
- pozitronová emisní tomografie MeSH
- prefrontální mozková kůra fyziologie MeSH
- receptory neurotransmiterů MeSH
- serotonin * fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Klíčová slova
- G proteiny, kontraktilita,
- MeSH
- adrenalin fyziologie MeSH
- adrenergní receptory fyziologie MeSH
- financování organizované MeSH
- kardiomyocyty fyziologie MeSH
- kontrakce myokardu fyziologie MeSH
- noradrenalin fyziologie MeSH
- proteiny vázající GTP fyziologie MeSH
- savci fyziologie MeSH
- srdce fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- adrenergní receptory fyziologie klasifikace MeSH
- agonisté adrenergních alfa-receptorů MeSH
- agonisté adrenergních beta-receptorů MeSH
- alfa blokátory klasifikace MeSH
- alfa-adrenergní receptory fyziologie klasifikace MeSH
- beta blokátory klasifikace MeSH
- beta-adrenergní receptory fyziologie klasifikace MeSH
- centrální nervový systém fyziologie MeSH
- chování MeSH
- financování organizované MeSH
- kognitivní poruchy MeSH
- lidé MeSH
- lokomoce MeSH
- noradrenalin fyziologie MeSH
- paměť MeSH
- pohybová aktivita MeSH
- pozornost MeSH
- učení MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
Mesenteric veins are more sensitive than arteries to the constrictor effects of sympathetic nerve stimulation and alpha-adrenoceptor agonists. We tested the hypothesis that alpha(1)- and alpha(2)-adrenoceptors interact to enhance adrenergic reactivity of mesenteric veins. We studied neurogenic and agonist-induced constrictions of mesenteric veins and arteries in vitro. Norepinephrine concentration-response curves were left-shifted in veins compared to arteries. UK 14,304 (0.01-1 microM, alpha(2)-adrenoceptor receptor agonist) did not constrict arteries or veins but enhanced constrictions and Ca(2+) signals mediated by alpha(1)-adrenoceptor stimulation in veins. Yohimbine (alpha(2)-adrenoceptor receptor antagonist) and MK912 (alpha(2C)-adrenoceptor receptor antagonist), but not alpha(2A)- or alpha(2B)-adrenoceptor antagonists, produced rightward shifts in norepinephrine concentration-response curves in veins. Pharmacological studies revealed that alpha(1D)-adrenoceptors mediate venous constrictions. Norepinephrine responses in veins from alpha(2C)-adrenoceptor knock-out (KO) mice were not different from wild type veins. Yohimbine inhibited norepinephrine constrictions in alpha(2C)-adrenoceptor KO veins suggesting that there is upregulation of other alpha(2)-adrenoceptors in alpha(2C)-KO mice. These data indicate that alpha(1D)- and alpha(2C)-adrenoceptors interact in veins but not in arteries. This interaction enhances venous adrenergic reactivity. Mesenteric vein-specific alpha(2)-adrenoceptor linked Ca(2+) and perhaps other signaling pathways account for enhanced venous adrenergic reactivity.
- MeSH
- alfa-1-adrenergní receptory - agonisté farmakologie MeSH
- alfa-1-adrenergní receptory metabolismus fyziologie MeSH
- alfa-2-adrenergní receptory - agonisté farmakologie MeSH
- alfa-2-adrenergní receptory - antagonisté farmakologie MeSH
- alfa-2-adrenergní receptory genetika metabolismus fyziologie MeSH
- arteriae mesentericae účinky léků fyziologie MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- noradrenalin fyziologie MeSH
- protein - isoformy antagonisté a inhibitory MeSH
- sympatický nervový systém účinky léků MeSH
- techniky in vitro MeSH
- vápníková signalizace účinky léků MeSH
- vazokonstrikce účinky léků MeSH
- vena mesenterica účinky léků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- srovnávací studie MeSH