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Abstract Background The R192Q mutation of the CACNA1A gene, encoding for the α1 subunit of voltage-gated P/Q Ca2+ channels (Cav2.1), is associated with familial hemiplegic migraine-1. We investigated whether this gain-of-function mutation changed the structure and function of trigeminal neuron P2X3 receptors that are thought to be important contributors to migraine pain. Results Using in vitro trigeminal sensory neurons of a mouse genetic model knockin for the CACNA1A R192Q mutation, we performed patch clamp recording and intracellular Ca2+ imaging that showed how these knockin ganglion neurons generated P2X3 receptor-mediated responses significantly larger than wt neurons. These enhanced effects were reversed by the Cav2.1 blocker ω-agatoxin. We, thus, explored intracellular signalling dependent on kinases and phosphatases to understand the molecular regulation of P2X3 receptors of knockin neurons. In such cells we observed strong activation of CaMKII reversed by ω-agatoxin treatment. The CaMKII inhibitor KN-93 blocked CaMKII phosphorylation and the hyperesponsive P2X3 phenotype. Although no significant difference in membrane expression of knockin receptors was found, serine phosphorylation of knockin P2X3 receptors was constitutively decreased and restored by KN-93. No change in threonine or tyrosine phosphorylation was detected. Finally, pharmacological inhibitors of the phosphatase calcineurin normalized the enhanced P2X3 receptor responses of knockin neurons and increased their serine phosphorylation. Conclusions The present results suggest that the CACNA1A mutation conferred a novel molecular phenotype to P2X3 receptors of trigeminal ganglion neurons via CaMKII-dependent activation of calcineurin that selectively impaired the serine phosphorylation state of such receptors, thus potentiating their effects in transducing trigeminal nociception.

The physical distancing measures necessitated by COVID-19 have resulted in a severe withdrawal from the patterns of daily life, necessitating significantly reduced contact with other people. To many, such withdrawal can be a major cause of distress. But, to some, this sort of withdrawal is an integral part of growth, a pathway to a more enriching life. The present study uses a sequential explanatory QUAN-qual design to investigate whether people who felt that their lives had changed for the better after being forced to engage in physical distancing, what factors predicted such well-being, and how they spent their time to generate this sense of well-being. We invited 614 participants who reported closely following physical distancing recommendations to complete a survey exploring this topic. Our analyses, after controlling for all other variables in the regression model, found a greater positive association between presence of meaning in life, coping style, and self-transcendent wisdom and residualized current well-being accounting for retrospective assessments of well-being prior to physical distancing. An extreme-case content analysis of participants' personal projects found that participants with low self-transcendent wisdom reported more survival-oriented projects (e.g., acquiring groceries or engaging in distracting entertainments), while participants reporting high self-transcendent wisdom reported more projects involving deepening interactions with other people, especially family. Our findings suggest a more nuanced pathway from adversity to a deeper sense of well-being by showing the importance of not merely coping with adversity, but truly transcending it. [ABSTRACT FROM AUTHOR]

Migraine patients often report (inter)ictal hypersensitivity to light, but the underlying mechanisms remain an enigma. Both hypo‐ and hyperresponsivity of the visual network have been reported, which may reflect either intra‐individual dynamics of the network or large inter‐individual variation in the measurement of human visual evoked potential data. Therefore, we studied visual system responsivity in freely behaving mice using combined epidural electroencephalography and intracortical multi‐unit activity to reduce variation in recordings and gain insight into visual cortex dynamics. For better clinical translation, we investigated transgenic mice that carry the human pathogenic R192Q missense mutation in the α1A subunit of voltage‐gated CaV2.1 Ca2+ channels leading to enhanced neurotransmission and familial hemiplegic migraine type 1 in patients. Visual evoked potentials were studied in response to visual stimulation paradigms with flashes of light. Following intensity‐dependent visual stimulation, FHM1 mutant mice displayed faster visual evoked potential responses, with lower initial amplitude, followed by less pronounced neuronal suppression compared to wild‐type mice. Similar to what was reported for migraine patients, frequency‐dependent stimulation in mutant mice revealed enhanced photic drive in the EEG beta‐gamma band. The frequency‐dependent increases in visual network responses in mutant mice may reflect the context‐dependent enhancement of visual cortex excitability, which could contribute to our understanding of sensory hypersensitivity in migraine. [ABSTRACT FROM AUTHOR]

This is the first electroencephalogram study exploring the personal perspective effect on wise advising. Participants advised hypothetical protagonists in life dilemmas from both the 2nd- and 3rd-person perspective. Their advice for each dilemma was rated by two independent raters on wisdom criteria, i.e., metacognitive humility, metacognitive flexibility, and perspective taking. The results revealed that participants felt a significantly shorter psychological distance from protagonists when advising from the 2nd- (vs. the 3rd-) person perspective, p < 0.001. However, there was no significant effect of perspective condition on the wisdom score. Nevertheless, stronger resting-state absolute EEG powers in the frontal lobe were associated with wiser advising from the 2nd-, but not the 3rd-person perspective. Moreover, Z tests revealed that the correlations between the resting-state absolute EEG powers and wisdom scores were significantly stronger during advising from the 2nd- than the 3rd-person perspective. These results suggest that advising from the 2nd-person perspective was more self-related, and mental activities during rest contributed to advising from the 2nd- but not the 3rd-person perspective. [ABSTRACT FROM AUTHOR]

This study investigates the relationship between motivation and the development of wisdom. Eighty Canadian participants were interviewed and completed Ardelt's Three-Dimensional Wisdom Scale (3D-WS). Using a mixed method design, we assessed wisdom definitions, interpersonal causal attributions, and mind-set about developing wisdom. A chi-square analysis revealed a significant relationship between attribution and mind-set about wisdom development. Two multivariate analyses of variance showed that both factors significantly influenced wisdom scores on the 3D-WS. These results suggest that people who consider wisdom development to be controllable and believe that their personal wisdom can be developed (i.e., growth mind-set) tend to be wiser, regardless of their definition of wisdom. By introducing the importance of mind-set and attribution, this study will open new avenues for research on teaching for wisdom and allow educators to develop programs to cultivate wisdom that focus on altering attribution and mind-set. [ABSTRACT FROM AUTHOR]

Although white matter lesions are frequently detected in migraine patients, underlying mechanisms remain unclear. Low carotid artery endothelial shear stress has been associated with white matter lesions. We aimed to investigate the association between carotid artery endothelial shear stress and white matter lesions in migraine. In 40 elderly migraine patients (n = 29 females, 75 years [SD 3]) and 219 controls (n = 80 females, 74 years [SD 3]) from the PROSPER-MRI study, carotid artery endothelial shear stress was estimated on 1.5 T gradient-echo phase contrast MRI. White matter lesion volumes were calculated from structural MRI scans. Analyses were adjusted for age, sex, cardiovascular risk factors and cardiovascular disease. Migraine patients had lower mean endothelial shear stress compared to controls (0.90 [SD 0.15] vs. 0.98 [SD 0.16] Pa; P = 0.03). The association between mean endothelial shear stress and white matter lesion volume was greater for the migraine group than control group (P for interaction = 0.05). Within the migraine group, white matter lesion volume increased with decreasing endothelial shear stress (β-0.421; P = 0.01). In conclusion, migraine patients had lower endothelial shear stress which was associated with higher white matter lesion volume. [ABSTRACT FROM AUTHOR]

We have introduced a common wisdom model to establish a shared language, clarify underlying theoretical assumptions, advance assessment tools, and foster evidence-based interventions for stimulating wisdom during challenging societal times. The common wisdom model synthesizes the views of numerous contemporary scientists working on wisdom and includes two components: perspectival meta-cognition and moral aspirations. Having received insightful commentaries on our model, here we consider the overall motivation for the model, address remaining jingle-jangle fallacies, clarify the meaning of morality for wisdom, and expand upon the relationship between moral and meta-cognitive components within the common wisdom model. We reflect on how the common wisdom model provides a nexus for integrating insights across multiple areas of research, affording plentiful opportunities for future research into wisdom's development, function, and underlying processes. We situate our reflections in the context of present-day pandemic-related uncertainties and unfolding societal shifts. [ABSTRACT FROM AUTHOR]

Interest in wisdom in the cognitive sciences, psychology, and education has been paralleled by conceptual confusions about its nature and assessment. To clarify these issues and promote consensus in the field, wisdom researchers met in Toronto in July of 2019, resolving disputes through discussion. Guided by a survey of scientists who study wisdom-related constructs, we established a common wisdom model, observing that empirical approaches to wisdom converge on the morally-grounded application of metacognition to reasoning and problem-solving. After outlining the function of relevant metacognitive and moral processes, we critically evaluate existing empirical approaches to measurement and offer recommendations for best practices. In the subsequent sections, we use the common wisdom model to selectively review evidence about the role of individual differences for development and manifestation of wisdom, approaches to wisdom development and training, as well as cultural, subcultural, and social-contextual differences. We conclude by discussing wisdom's conceptual overlap with a host of other constructs and outline unresolved conceptual and methodological challenges. [ABSTRACT FROM AUTHOR]

Cluster headache is characterised by attacks of excruciating unilateral headache or facial pain lasting 15 min to 3 h and is seen as one of the most intense forms of pain. Cluster headache attacks are accompanied by ipsilateral autonomic symptoms such as ptosis, miosis, redness or flushing of the face, nasal congestion, rhinorrhoea, peri-orbital swelling and/or restlessness or agitation. Cluster headache treatment entails fast-acting abortive treatment, transitional treatment and preventive treatment. The primary goal of prophylactic and transitional treatment is to achieve attack freedom, although this is not always possible. Subcutaneous sumatriptan and high-flow oxygen are the most proven abortive treatments for cluster headache attacks, but other treatment options such as intranasal triptans may be effective. Verapamil and lithium are the preventive drugs of first choice and the most widely used in first-line preventive treatment. Given its possible cardiac side effects, electrocardiogram (ECG) is recommended before treating with verapamil. Liver and kidney functioning should be evaluated before and during treatment with lithium. If verapamil and lithium are ineffective, contraindicated or discontinued because of side effects, the second choice is topiramate. If all these drugs fail, other options with lower levels of evidence are available (e.g. melatonin, clomiphene, dihydroergotamine, pizotifen). However, since the evidence level is low, we also recommend considering one of several neuromodulatory options in patients with refractory chronic cluster headache. A new addition to the preventive treatment options in episodic cluster headache is galcanezumab, although the long-term effects remain unknown. Since effective preventive treatment can take several weeks to titrate, transitional treatment can be of great importance in the treatment of cluster headache. At present, greater occipital nerve injection is the most proven transitional treatment. Other options are high-dose prednisone or frovatriptan. [ABSTRACT FROM AUTHOR]

Background: Patients with migraine might be more susceptible of spreading depolarizations, which are known to affect vascular and neuronal function and penumbra recovery after stroke. We investigated whether these patients have more severe stroke progression and less favorable outcomes after recanalization therapy. Methods: We included patients from a prospective multicenter ischemic stroke cohort. Lifetime migraine history was based on the International Classification of Headache Disorders II criteria. Patients without confirmed migraine diagnosis were excluded. Patients underwent CT angiography and CT perfusion <9 h of onset and follow-up CT after three days. On admission, presence of a perfusion deficit, infarct core and penumbra volume, and blood brain barrier permeability (BBBP) were assessed. At follow-up we assessed malignant edema, hemorrhagic transformation, and final infarct volume. Outcome at three months was evaluated with the modified Rankin Scale (mRS). We calculated adjusted relative risks (aRR) or difference of means (aB) with regression analyses. Results: We included 600 patients of whom 43 had migraine. There were no differences between patients with or without migraine in presence of a perfusion deficit on admission (aRR: 0.98, 95%CI: 0.77–1.25), infarct core volume (aB: -10.8, 95%CI: -27.04–5.51), penumbra volume (aB: -11.6, 95%CI: -26.52–3.38), mean blood brain barrier permeability (aB: 0.08, 95%CI: -3.11–2.96), malignant edema (0% vs. 5%), hemorrhagic transformation (aRR: 0.26, 95%CI: 0.04–1.73), final infarct volume (aB: -14.8, 95%CI: 29.9–0.2) or outcome after recanalization therapy (mRS > 2, aRR: 0.50, 95%CI: 0.21–1.22). Conclusion: Elderly patients with a history of migraine do not seem to have more severe stroke progression and have similar treatment outcomes compared with patients without migraine. [ABSTRACT FROM AUTHOR]

Scholars within the Berlin paradigm have analysed participants' responses to a hypothetical vignette about a friend's suicide ideation. However, no study has yet focused on participants' emotional reactions to this scenario, an important aspect of wisdom performance. We conducted a Thin‐Slice Wisdom study where participants were asked to give advice to a hypothetical friend contemplating suicide. We analysed their emotional profiles using facial expression analysis software (FACET2.1 and FACEREADER7.1). Participants' verbal responses were also transcribed and then scored by 10 raters using the Berlin criteria. Results revealed that the sadder the participants felt, the wiser their performance. Wiser participants may have been better at exploring this sad, but true, existential human dilemma. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s12144-022-02816-6Correction to: Current Psychology (2021)https://doi.org/10.1007/s12144-022-02816-6The original version of this article unfortunately contained a mistake. The right affiliation of Fengyan Wang and Juan Shi has been corrected.The original article has been corrected.Publisher's noteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.By Kaili Zhang; Juan Shi; Fengyan Wang and Michel FerrariReported by Author; Author; Author; Author [Extracted from the article]