Signalling
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OBJECTIVE: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. METHODS: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. RESULTS: When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. CONCLUSIONS: This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.
- MeSH
- dospělí MeSH
- interocepce * fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mapování mozku MeSH
- mladý dospělý MeSH
- mozek * patofyziologie diagnostické zobrazování MeSH
- nemoci nervového systému * patofyziologie diagnostické zobrazování MeSH
- pozornost fyziologie MeSH
- srdeční frekvence fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Asymmetric or unilateral hearing loss (AHL) may cause irreversible changes in the processing of acoustic signals in the auditory system. We aim to provide a comprehensive view of the auditory processing abilities for subjects with acquired AHL, and to examine the influence of AHL on speech perception under difficult conditions, and on auditory temporal and intensity processing. DESIGN: We examined peripheral and central auditory functions for 25 subjects with AHL resulting from vestibular schwannoma, and compared them to those from 24 normal-hearing controls that were matched with the AHL subjects in mean age and hearing thresholds in the healthy ear. Besides the basic hearing threshold assessment, the tests comprised the detection of tones and gaps in a continuous noise, comprehension of speech in babble noise, binaural interactions, difference limen of intensity, and detection of frequency modulation. For the AHL subjects, the selected tests were performed separately for the healthy and diseased ear. RESULTS: We observed that binaural speech comprehension, gap detection, and frequency modulation detection abilities were dominated by the healthy ear and were comparable for both groups. The AHL subjects were less sensitive to interaural delays, however, they exhibited a higher sensitivity to sound level, as indicated by lower difference limen of intensity and a higher sensitivity to interaural intensity difference. Correlations between the individual test scores indicated that speech comprehension by the AHL subjects was associated with different auditory processing mechanisms than for the control subjects. CONCLUSIONS: The data suggest that AHL influences both peripheral and central auditory processing abilities and that speech comprehension under difficult conditions relies on different mechanisms for the AHL subjects than for normal-hearing controls.
- MeSH
- dospělí MeSH
- jednostranná nedoslýchavost * patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- percepce řeči * fyziologie MeSH
- senioři MeSH
- sluchová percepce fyziologie MeSH
- sluchový práh * MeSH
- studie případů a kontrol MeSH
- vestibulární schwannom * patofyziologie komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Background: Activation of cannabinoid receptor 1 (CB1R) in the nervous system modulates the processing of acute and chronic pain. CB1R activity is regulated by desensitization and internalization. SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1) inhibits the internalization of CB1R. This causes increased and prolonged association of the desensitized receptor with G protein-coupled receptor kinase 3 (GRK3) and beta-arrestin on the cell membrane and results in decreased activation of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Genetic deletion of SGIP1 in mice leads to altered CB1R-related functions, such as decreased anxiety-like behaviors, modified cannabinoid tetrad behaviors, reduced acute nociception, and increased sensitivity to analgesics. In this work, we asked if deletion of SGIP1 affects chronic nociception and analgesic effect of Δ9-tetrahydrocannabinol (THC) and WIN 55,212-2 (WIN) in mice. Methods: We measured tactile responses of hind paws to increasing pressure in wild-type and SGIP1 knock-out mice. Inflammation in the paw was induced by local injection of carrageenan. To determine the mechanical sensitivity, the paw withdrawal threshold (PWT) was measured using an electronic von Frey instrument with the progression of the applied force. Results: The responses to mechanical stimuli varied depending on the sex, genotype, and treatment. SGIP1 knock-out male mice exhibited lower PWT than wild-type males. On the contrary, the female mice exhibited comparable PWT. Following THC or WIN treatment in male mice, SGIP1 knock-out males exhibited PWT lower than wild-type males. THC treatment in SGIP1 knock-out females resulted in PWT higher than after THC treatment of wild-type females. However, SGIP1 knock-out and wild-type female mice exhibited similar PWT after WIN treatment. Conclusions: We provide evidence that SGIP1, possibly by interacting with CB1R, is involved in processing the responses to chronic pain. The absence of SGIP1 results in enhanced sensitivity to mechanical stimuli in males, but not females. The antinociceptive effect of THC is superior to that of WIN in SGIP1 knock-out mice in the carrageenan-induced model of chronic pain.
- MeSH
- benzoxaziny * farmakologie MeSH
- hyperalgezie * genetika MeSH
- morfoliny farmakologie MeSH
- myši inbrední C57BL MeSH
- myši knockoutované * MeSH
- myši MeSH
- naftaleny MeSH
- nocicepce účinky léků MeSH
- receptor kanabinoidní CB1 * genetika metabolismus MeSH
- tetrahydrokanabinol * farmakologie MeSH
- zánět * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- zdánlivý pohyb,
- MeSH
- lidé MeSH
- oči MeSH
- péče o sebe * metody MeSH
- počítače MeSH
- pohybová aktivita MeSH
- pohyby očí MeSH
- relaxační terapie metody MeSH
- zrak * MeSH
- zraková percepce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- populární práce MeSH
- Klíčová slova
- čakry,
- MeSH
- adaptace na tmu * MeSH
- lidé MeSH
- meditace metody MeSH
- melatonin terapeutické užití MeSH
- oči MeSH
- oční nemoci terapie MeSH
- poruchy zraku terapie MeSH
- relaxační terapie metody MeSH
- senzorická deprivace MeSH
- spirituální terapie metody MeSH
- zrak MeSH
- Check Tag
- lidé MeSH
We investigated neural correlates of Emotion Recognition Accuracy (ERA) using the Assessment of Contextualized Emotions (ACE). ACE infuses context by presenting emotion expressions in a naturalistic group setting and distinguishes between accurately perceiving intended emotions (signal), and bias due to perceiving additional, secondary emotions (noise). This social perception process is argued to induce perspective taking in addition to pattern matching in ERA. Thirty participants were presented with an fMRI-compatible adaptation of the ACE consisting of blocks of neutral and emotional faces in single and group-embedded settings. Participants rated the central character's expressions categorically or using scalar scales in consequent fMRI scans. Distinct brain activations were associated with the perception of emotional vs. neutral faces in the four conditions. Moreover, accuracy and bias scores from the original ACE task performed on another day were associated with brain activation during the scalar (vs. categorical) condition for emotional (vs. neutral) faces embedded in group. These findings suggest distinct cognitive mechanisms linked to each type of emotional rating and highlight the importance of considering cognitive bias in the assessment of social emotion perception.
- MeSH
- dospělí MeSH
- emoce * fyziologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mapování mozku * MeSH
- mladý dospělý MeSH
- mozek * fyziologie diagnostické zobrazování MeSH
- rozpoznání obličeje fyziologie MeSH
- sociální percepce * MeSH
- světelná stimulace metody MeSH
- výraz obličeje * MeSH
- zkreslení výsledků (epidemiologie) MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Three decades ago, the first endocannabinoid, anandamide (AEA), was identified, and its analgesic effect was recognized in humans and preclinical models. However, clinical trial failures pointed out the complexity of the AEA-induced analgesia. The first synapses in the superficial laminae of the spinal cord dorsal horn represent an important modulatory site in nociceptive transmission and subsequent pain perception. The glutamatergic synaptic transmission at these synapses is strongly modulated by two primary AEA-activated receptors, cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1), both highly expressed on the presynaptic side formed by the endings of primary nociceptive neurons. Activation of these receptors can have predominantly inhibitory (CB1) and excitatory (TRPV1) effects that are further modulated under pathological conditions. In addition, dual AEA-mediated signaling and action may occur in primary sensory neurons and dorsal horn synapses. AEA application causes balanced inhibition and excitation of primary afferent synaptic input on superficial dorsal horn neurons in normal conditions, whereas peripheral inflammation promotes AEA-mediated inhibition. This review focuses mainly on the modulation of synaptic transmission at the spinal cord level and signaling in primary nociceptive neurons by AEA via CB1 and TRPV1 receptors. Furthermore, the spinal analgesic effect in preclinical studies and clinical aspects of AEA-mediated analgesia are considered.
- MeSH
- endokanabinoidy * metabolismus MeSH
- kationtové kanály TRPV metabolismus MeSH
- kyseliny arachidonové * metabolismus farmakologie MeSH
- lidé MeSH
- mícha * metabolismus účinky léků MeSH
- nervový přenos * fyziologie účinky léků MeSH
- nocicepce fyziologie účinky léků MeSH
- nociceptory metabolismus účinky léků fyziologie MeSH
- polynenasycené alkamidy * metabolismus MeSH
- receptor kanabinoidní CB1 metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways. METHODS: A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review. RESULTS: We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development. CONCLUSIONS: Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.
- MeSH
- bolest MeSH
- buněčný převod mechanických signálů * fyziologie MeSH
- migréna * diagnóza MeSH
- nocicepce fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- systematický přehled MeSH
INTRODUCTION: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year. METHODS: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52. RESULTS: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) μm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified. CONCLUSION: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540954.
- MeSH
- injekce intravitreální MeSH
- lidé středního věku MeSH
- lidé MeSH
- makulární degenerace * farmakoterapie MeSH
- receptory vaskulárního endoteliálního růstového faktoru * terapeutické užití MeSH
- rekombinantní fúzní proteiny * terapeutické užití MeSH
- senioři MeSH
- výsledek terapie MeSH
- zraková ostrost MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- hodnocení ekvivalence MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
Background: Visual occlusion reduces players' field of vision and directly affects their physical, technical and positional performance. Therefore, it is important to understand how visual perception is affected, and whether training with visual occlusion leads to an improvement in performance.Objective: This study aimed to examine whether training with visual occlusion could improve technical skills in young football players. Methods: Thirty male Under-14 amateur football players were randomly assigned to a visual occlusion group (OCC; n = 15) and a control group (CON; n = 15). In addition to the conventional training program, the OCC performed visual occlusion training sessions using spatial occlusion goggles that removed the sight of the participants' limbs and lower body. The CON performed only the conventional training program. The study consisted of a pre-test, two months of training intervention and a post-test. Contextualised technical skills were tested using the Loughborough Soccer Passing Test. Results: Both OCC (p = .21) and CON (p = .43) did not change Trial performance. However, the OCC experienced small-to-moderate improvements in Penalty time (p = .002; d = 0.51, 95% CI [0.10, 0.70]) and Global performance (p = .005, d = 0.44, 95% CI [0.05, 0.66]). The CON did not show changes in Penalty time (p = .61) and Global performance (p = .89) variables. A significant moment × group interaction was found in Penalty time (p = .016, ηp2 = .19, 95% CI [.03, .48]) and Global performance (p = .011, ηp2 = .21, 95% CI [.01, .45]). Conclusions: The OCC has shown a significant reduction in the amount of time required to complete the trial and the Penalty time. These results suggest that incorporating visual occlusion as a paradigm into a training program for football players may positively impact their technical skills.