| 1. |
- Ali, Muhaddisa Barat, 1986, et al.
(författare)
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Domain Mapping and Deep Learning from Multiple MRI Clinical Datasets for Prediction of Molecular Subtypes in Low Grade Gliomas
- 2020
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Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 10:7, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- Brain tumors, such as low grade gliomas (LGG), are molecularly classified which require the surgical collection of tissue samples. The pre-surgical or non-operative identification of LGG molecular type could improve patient counseling and treatment decisions. However, radiographic approaches to LGG molecular classification are currently lacking, as clinicians are unable to reliably predict LGG molecular type using magnetic resonance imaging (MRI) studies. Machine learning approaches may improve the prediction of LGG molecular classification through MRI, however, the development of these techniques requires large annotated data sets. Merging clinical data from different hospitals to increase case numbers is needed, but the use of different scanners and settings can affect the results and simply combining them into a large dataset often have a significant negative impact on performance. This calls for efficient domain adaption methods. Despite some previous studies on domain adaptations, mapping MR images from different datasets to a common domain without affecting subtitle molecular-biomarker information has not been reported yet. In this paper, we propose an effective domain adaptation method based on Cycle Generative Adversarial Network (CycleGAN). The dataset is further enlarged by augmenting more MRIs using another GAN approach. Further, to tackle the issue of brain tumor segmentation that requires time and anatomical expertise to put exact boundary around the tumor, we have used a tight bounding box as a strategy. Finally, an efficient deep feature learning method, multi-stream convolutional autoencoder (CAE) and feature fusion, is proposed for the prediction of molecular subtypes (1p/19q-codeletion and IDH mutation). The experiments were conducted on a total of 161 patients consisting of FLAIR and T1 weighted with contrast enhanced (T1ce) MRIs from two different institutions in the USA and France. The proposed scheme is shown to achieve the test accuracy of 74.81% on 1p/19q codeletion and 81.19% on IDH mutation, with marked improvement over the results obtained without domain mapping. This approach is also shown to have comparable performance to several state-of-the-art methods.
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| 2. |
- Alonso, Fabiola, et al.
(författare)
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Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems : A Simulation Study
- 2018
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome
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| 3. |
- Alonso, Fabiola, et al.
(författare)
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Investigation into Deep Brain Stimulation Lead Designs : A Patient-Specific Simulation Study
- 2016
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 6:3, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a “virtual” ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode.
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| 4. |
- Anzani, S, et al.
(författare)
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OXTR Gene DNA Methylation Levels Are Associated with Discounting Behavior with Untrustworthy Proposers
- 2022
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Individual differences in temporal and probabilistic discounting are associated with a wide range of life outcomes in literature. Traditional approaches have focused on impulsiveness and cognitive control skills, on goal-oriented personality traits as well as on the psychological perception of time. More recently, literature started to consider the role of social and contextual factors in discounting behavior. Between others, higher generalized trust in human beings and specific trust in people who will deliver the future/probabilistic rewards have been related to a stronger willingness to wait and to assume risk. Moreover, the tendency to trust others has been associated with the oxytocin receptor gene regulation that can be modified by life experiences. In this perspective, we hypothesized that differences in the tendency to wait and to take risks for a more desirable reward according to the proposer’s trustworthiness could be related to a different level of DNA methylation at the oxytocin receptor gene. Findings confirmed that participants are less willing to wait and to risk when the proposer is considered highly untrustworthy and revealed how higher oxytocin receptor gene DNA methylation is associated with a stronger effect due to the presence of an untrustworthy proposer. Limits and future directions are outlined.
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| 5. |
- Barua, Shaibal, et al.
(författare)
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Towards Intelligent Data Analytics : A Case Study in Driver Cognitive Load Classification
- 2020
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Ingår i: Brain Sciences. - Switzerland : MDPI AG. - 2076-3425. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- One debatable issue in traffic safety research is that cognitive load by secondary tasks reduces primary task performance, i.e., driving. In this paper, the study adopted a version of the n-back task as a cognitively loading secondary task on the primary task i.e., driving; where drivers drove in three different simulated driving scenarios. This paper has taken a multimodal approach to perform ‘intelligent multivariate data analytics’ based on machine learning (ML). Here, k-nearest neighbour (k-NN), support vector machine (SVM) and random forest (RF) are used for driver cognitive load classification. Moreover, physiological measures have proven to be sophisticated in cognitive load identification, yet it suffers from confounding factors and noise. Therefore, this work uses multi-component signals, i.e., physiological measures and vehicular features to overcome that problem. Both multiclass and binary classifications have been performed to distinguish normal driving from cognitive load tasks. To identify the optimal feature set, two feature selection algorithms, i.e., Sequential Forward Floating Selection (SFFS) and Random Forest have been applied where out of 323 features, a sub-set of 42 features has been selected as the best feature subset. For the classification, the RF has shown better performance with F1-score of 0.75 and 0.80 than two other algorithms. Also, the result shows that using multicomponent features classifiers could classify better than using features from a single source.
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| 6. |
- Belin, Andrea Carmine, et al.
(författare)
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Calcitonin gene-related peptide (CGRP) and cluster headache
- 2020
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Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 10:1
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Forskningsöversikt (refereegranskat)abstract
- Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP receptor complex have recently taken center stage as therapeutic targets for primary headaches, such as migraine. Multiple CGRP and CGRP receptor monoclonal antibodies, as well as small molecule antagonists (gepants) are on their way constituting a new frontier of migraine and possibly CH medication. During a CH attack, there is an activation of the trigeminal-autonomic reflex with the release of CGRP, and inversely if CGRP is administered to a CH patient in an active disease phase, it triggers an attack. Increased levels of CGRP have been found in ipsilateral jugular vein blood during the active phase of CH. This process is hypothesized to have a key role in the intense pain perception and in the associated distinctive vasodilation. So far, clinical tests of CGRP antibodies have been inconclusive in CH patients. This review summarizes the current state of knowledge on the role of CGRP in CH pathology, and as a target for future treatments.
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| 7. |
- Bergen, K., et al.
(författare)
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Neurite Growth and Polarization on Vitronectin Substrate after in Vitro Trauma is not Enhanced after IGF Treatment
- 2018
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Following traumatic brain injuries (TBI), insulin-like growth factor (IGF) is cortically widely upregulated. This upregulation has a potential role in the recovery of neuronal tissue, plasticity, and neurotrophic activity, though the molecular mechanisms involved in IGF regulation and the exact role of IGF after TBI remain unclear. Vitronectin (VN), an extracellular matrix (ECM) molecule, has recently been shown to be of importance for IGF-mediated cellular growth and migration. Since VN is downregulated after TBI, we hypothesized that insufficient VN levels after TBI impairs the potential beneficial activity of IGF. To test if vitronectin and IGF-1/IGFBP-2 could contribute to neurite growth, we cultured hippocampal neurons on +/- vitronectin-coated coverslips and them treated with +/- IGF-1/IGF binding protein 2 (IGFBP-2). Under same conditions, cell cultures were also subjected to in vitro trauma to investigate differences in the posttraumatic regenerative capacity with +/- vitronectin-coated coverslips and with +/- IGF-1/IGFBP-2 treatment. In both the control and trauma situations, hippocampal neurons showed a stronger growth pattern on vitronectin than on the control substrate. Surprisingly, the addition of IGF-1/IGFBP-2 showed a decrease in neurite growth. Since neurite growth was measured as the number of neurites per area, we hypothesized that IGF-1/IGFBP-2 contributes to the polarization of neurons and thus induced a less dense neurite network after IGF-1/IGFBP-2 treatment. This hypothesis could not be confirmed and we therefore conclude that vitronectin has a positive effect on neurite growth in vitro both under normal conditions and after trauma, but that addition of IGF-1/IGFBP-2 does not have a positive additive effect.
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| 8. |
- Böhme, Rebecca, et al.
(författare)
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Anhedonia to Gentle Touch in Fibromyalgia: Normal Sensory Processing but Abnormal Evaluation
- 2020
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Social touch is important for interpersonal interaction. Gentle touch and slow brushing are typically perceived as pleasant, the degree of pleasantness is linked to the activity of the C-tactile (CT) fibers, a class of unmyelinated nerves in the skin. The inability to experience pleasure in general is called anhedonia, a common phenomenon in the chronic pain condition fibromyalgia. Here, we studied the perception and cortical processing of gentle touch in a well-characterized cohort of fibromyalgia. Patients and controls participated in functional brain imaging while receiving tactile stimuli (brushing) on the forearm. They were asked to provide ratings of pleasantness of the tactile stimulus and ongoing pain. We found high distress, pain catastrophizing, and insomnia, and a low perceived state of health in fibromyalgia. Further, patients rated both slow (CT-optimal) and fast (CT-suboptimal) brushing as less pleasant than healthy participants. While there was no difference in brain activity during touch, patients showed deactivation in the right posterior insula (contralateral to the stimulated arm) during pleasantness rating and activation during pain rating. The opposite pattern was observed in healthy participants. Voxel-based morphometry analysis revealed reduced grey matter density in patients, in the bilateral hippocampus and anterior insula. Our results suggest anhedonia to gentle touch in fibromyalgia with intact early-stage sensory processing but dysfunctional evaluative processing. These findings contribute to our understanding of the mechanisms underlying anhedonia in fibromyalgia.
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| 9. |
- Frick, Claudia, et al.
(författare)
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Age-Dependency of Neurite Outgrowth in Postnatal Mouse Cochlear Spiral Ganglion Explants
- 2020
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The spatial gap between cochlear implants (CIs) and the auditory nerve limits frequency selectivity as large populations of spiral ganglion neurons (SGNs) are electrically stimulated synchronously. To improve CI performance, a possible strategy is to promote neurite outgrowth toward the CI, thereby allowing a discrete stimulation of small SGN subpopulations. Brain-derived neurotrophic factor (BDNF) is effective to stimulate neurite outgrowth from SGNs.Method: TrkB (tropomyosin receptor kinase B) agonists, BDNF, and five known small-molecule BDNF mimetics were tested for their efficacy in stimulating neurite outgrowth in postnatal SGN explants. To modulate Trk receptor-mediated effects, TrkB and TrkC ligands were scavenged by an excess of recombinant receptor proteins. The pan-Trk inhibitor K252a was used to block Trk receptor actions.Results: THF (7,8,3 '-trihydroxyflavone) partly reproduced the BDNF effect in postnatal day 7 (P7) mouse cochlear spiral ganglion explants (SGEs), but failed to show effectiveness in P4 SGEs. During the same postnatal period, spontaneous and BDNF-stimulated neurite outgrowth increased. The increased neurite outgrowth in P7 SGEs was not caused by the TrkB/TrkC ligands, BDNF and neurotrophin-3 (NT-3).Conclusions: The age-dependency of induction of neurite outgrowth in SGEs was very likely dependent on presently unidentified factors and/or molecular mechanisms which may also be decisive for the age-dependent efficacy of the small-molecule TrkB receptor agonist THF.
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| 10. |
- Hornsby, N, et al.
(författare)
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The Use of Magnetic Resonance Imaging Techniques in Assessing the Effects of Alcohol Consumption and Heavy Drinking on the Adolescent Brain: A Scoping Review Protocol
- 2021
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Alcohol consumption, specifically heavy drinking during adolescence, has been shown to be accompanied by adverse structural brain changes in adolescent drinkers. This scoping review will aim to quantify and evaluate the quality of studies in which magnetic resonance imaging (MRI) techniques are used to assess regional brain deficits among adolescents who consume alcohol. Methods and analysis: This scoping review will be conducted following the Arksey and O’Malley scoping review methodology framework and will be reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews (PRISMA-ScR) guidelines. Literature will be searched for the period January 1999 to March 2021. Two reviewers will independently screen titles/abstracts and full-texts in two consecutive screening stages. Eligible studies will be independently reviewed to ensure that inclusion criteria are met. Cohen’s Kappa (κ) will be used to calculate inter-rater agreement. A third reviewer will resolve any disagreements. The Joanna Briggs Institute (JBI) Appraisal Tools will be used for quality appraisal of the included studies. Findings will be reported by means of a narrative overview, tabular presentation of study characteristics, and quality assessment, and a thematic analysis of major themes. This scoping review has been registered with the Open Science Framework. Ethics and dissemination: Scoping reviews do not require ethical approval, however, this review forms part of a larger study that has obtained approval from the Faculty of Health and Medical Sciences, Health Research Ethics Committee at Stellenbosch University (S20/04/086). Findings will be disseminated by means of peer-reviewed publications and conferences.
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| 11. |
- Islam, Mir Riyanul, Doctoral Student, 1991-, et al.
(författare)
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A Novel Mutual Information based Feature Set for Drivers’ Mental Workload Evaluation Using Machine Learning
- 2020
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Ingår i: Brain Sciences. - Switzerland : MDPI AG. - 2076-3425. ; 10:8, s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of physiological signals, electroencephalography in more specific notion, is considered as a very promising technique to obtain objective measures for mental workload evaluation, however, it requires complex apparatus to record and thus with poor usability in monitoring in-vehicle drivers’mental workload. This study proposes amethodology of constructing a novel mutual information-based feature set from the fusion of electroencephalography and vehicular signals acquired through real driving experiment and deployed in evaluating drivers’ mental workload. Mutual information of electroencephalography and vehicular signals were used as the prime factor for the fusion of features. In order to assess the reliability of the developed feature set mental workload score prediction, classification and event classification tasks were performed using different machine learning models. Moreover, features extracted from electroencephalography were used to compare the performance. In the prediction of mental workload score, expert-defined scores were used as the target values. For classification tasks, true labels were set from contextual information of the experiment. An extensive evaluation of every prediction tasks was carried out using different validation methods. In predicting mental workload score from the proposed feature set lowest mean absolute error was 0.09 and for classifying mental workload highest accuracy was 94%. According to the outcome of the study, it can be stated that the novel mutual information based features developed through the proposed approach can be employed to classify and monitor in-vehicle drivers’ mental workload.
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| 12. |
- Jiang, MF, et al.
(författare)
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Image Classification of Alzheimer's Disease Based on External-Attention Mechanism and Fully Convolutional Network
- 2022
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Automatic and accurate classification of Alzheimer’s disease is a challenging and promising task. Fully Convolutional Network (FCN) can classify images at the pixel level. Adding an attention mechanism to the Fully Convolutional Network can effectively improve the classification performance of the model. However, the self-attention mechanism ignores the potential correlation between different samples. Aiming at this problem, we propose a new method for image classification of Alzheimer’s disease based on the external-attention mechanism. The external-attention module is added after the fourth convolutional block of the fully convolutional network model. At the same time, the double normalization method of Softmax and L1 norm is introduced to obtain a better classification performance and richer feature information of the disease probability map. The activation function Softmax can increase the degree of fitting of the neural network to the training set, which transforms linearity into nonlinearity, thereby increasing the flexibility of the neural network. The L1 norm can avoid the attention map being affected by especially large (especially small) eigenvalues. The experiments in this paper use 550 three-dimensional MRI images and use five-fold cross-validation. The experimental results show that the proposed image classification method for Alzheimer’s disease, combining the external-attention mechanism with double normalization, can effectively improve the classification performance of the model. With this method, the accuracy of the MLP-A model is 92.36%, the accuracy of the MLP-B model is 98.55%, and the accuracy of the fusion model MLP-C is 98.73%. The classification performance of the model is higher than similar models without adding any attention mechanism, and it is better than other comparison methods.
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| 13. |
- Kang, Jie, et al.
(författare)
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Aerobic exercise prevents depression via alleviating hippocampus injury in chronic stressed depression rats
- 2021
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Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 11:1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Depression is one of the overwhelming public health problems. Alleviating hippocampus injury may prevent depression development. Herein, we established the chronic unpredictable mild stress (CUMS) model and aimed to investigate whether aerobic exercise (AE) could alleviate CUMS induced depression-like behaviors and hippocampus injury. (2) Methods: Forty-eight healthy male Sprague-Dawley rats (200 ± 20 g) were randomly divided into 4 groups (control, CUMS, CUMS + 7 days AE, CUMS + 14 days AE). Rats with AE treatments were subjected to 45 min treadmill per day. (3) Results: AE intervention significantly improved CUMS-induced depressive behaviors, e.g., running square numbers and immobility time assessed by the open field and forced swimming test, suppressed hippocampal neuron apoptosis, reduced levels of phosphorylation of NMDA receptor and homocysteine in hippocampus, as well as serum glucocorticoids, compared to the CUMS rats. In contrast, AE upregulated phosphorylation of AMPAR receptor and brain-derived neurotrophic factor (BDNF) hippocampus in CUMS depression rats. The 14 day-AE treatment exhibited better performance than 7 day-AE on the improvement of the hippocampal function. (4) Conclusion: AE might be an efficient strategy for prevention of CUMS-induced depression via ameliorating hippocampus functions. Underlying mechanisms may be related with glutamatergic system, the neurotoxic effects of homocysteine, and/or influences in glucocorticoids-BDNF expression interaction.
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| 14. |
- Lee, Jinhee, et al.
(författare)
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Genetic Variation and Autism : A Field Synopsis and Systematic Meta-Analysis
- 2020
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to verify noteworthy findings between genetic risk factors and autism spectrum disorder (ASD) by employing the false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP). PubMed and the Genome-Wide Association Studies (GWAS) catalog were searched from inception to 1 August, 2019. We included meta-analyses on genetic factors of ASD of any study design. Overall, twenty-seven meta-analyses articles from literature searches, and four manually added articles from the GWAS catalog were re-analyzed. This showed that five of 31 comparisons for meta-analyses of observational studies, 40 out of 203 comparisons for the GWAS meta-analyses, and 18 out of 20 comparisons for the GWAS catalog, respectively, had noteworthy estimations under both Bayesian approaches. In this study, we found noteworthy genetic comparisons highly related to an increased risk of ASD. Multiple genetic comparisons were shown to be associated with ASD risk; however, genuine associations should be carefully verified and understood.
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| 15. |
- Lindblom, Julius, et al.
(författare)
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Biomarkers in Neuropsychiatric Systemic Lupus Erythematosus : A Systematic Literature Review of the Last Decade
- 2022
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 12:2
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Forskningsöversikt (refereegranskat)abstract
- Nervous system involvement in patients with SLE, termed neuropsychiatric SLE (NPSLE), constitutes a diagnostic challenge, and its management is still poorly optimised. This review summarises recent insights over the past decade in laboratory biomarkers of diagnosis, monitoring, and prognosis of NPSLE. An initial systematic search in the Medline and Web of Science was conducted to guide the selection of articles. Emerging diagnostic biomarkers in NPSLE that displayed satisfactory ability to discriminate between NPSLE and controls include serum interleukin (IL)-6, microRNA (miR)-23a, miR-155, and cerebrospinal fluid (CSF) α-Klotho. CSF lipocalin-2, macrophage colony-stimulating factor (M-CSF), and immunoglobulin (Ig)M also displayed such ability in two ethnically diverse cohorts. Serum interferon (IFN)-α and neuron specific enolase (NSE) were recently reported to moderately correlate with disease activity in patients with active NPSLE. CSF IL-8, IL-13, and granulocyte colony-stimulating factor (G-CSF) exhibited excellent sensitivity, yet poorer specificity, as predictors of response to therapy in patients with NPSLE. The overall lack of validation studies across multiple and diverse cohorts necessitates further and well-concerted investigations. Nevertheless, we propound CSF lipocalin 2 among molecules that hold promise as reliable diagnostic biomarkers in NPSLE.
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| 16. |
- Lopachev, Alexander, V, et al.
(författare)
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Ouabain-Induced Gene Expression Changes in Human iPSC-Derived Neuron Culture Expressing Dopamine and cAMP-Regulated Phosphoprotein 32 and GABA Receptors
- 2021
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Cardiotonic steroids (CTS) are specific inhibitors and endogenous ligands of a key enzyme in the CNS-the Na+, K+-ATPase, which maintains and creates an ion gradient on the plasma membrane of neurons. CTS cause the activation of various signaling cascades and changes in gene expression in neurons and other cell types. It is known that intracerebroventricular injection of cardiotonic steroid ouabain causes mania-like behavior in rodents, in part due to activation of dopamine-related signaling cascades in the dopamine and cAMP-regulated phosphoprotein 32 (DARPP-32) expressing medium spiny neurons in the striatum. Dopaminergic projections in the striatum innervate these GABAergic medium spiny neurons. The objective of this study was to assess changes in the expression of all genes in human iPSC-derived expressing DARPP-32 and GABA receptors neurons under the influence of ouabain. We noted a large number of statistically significant upregulated and downregulated genes after a 16-h incubation with non-toxic concentration (30 nM) of ouabain. These changes in the transcriptional activity were accomplished with activation of MAP-kinase ERK1/2 and transcriptional factor cAMP response element-binding protein (CREB). Thus, it can be concluded that 30 nM ouabain incubated for 16 h with human iPSC-derived expressing DARPP-32 and GABA receptors neurons activates genes associated with neuronal maturation and synapse formation, by increasing the expression of genes associated with translation, vesicular transport, and increased electron transport chain function. At the same time, the expression of genes associated with proliferation, migration, and early development of neurons decreases. These data indicate that non-toxic concentrations of ouabain may induce neuronal maturation, neurite growth, and increased synaptogenesis in dopamine-receptive GABAergic neurons, suggesting formation of plasticity and the establishment of new neuronal junctions.
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| 17. |
- Losurdo, Michela, et al.
(författare)
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Diffuse Axonal Injury in the Rat Brain: Axonal Injury and Oligodendrocyte Activity Following Rotational Injury
- 2020
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Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) commonly results in primary diffuse axonal injury (DAI) and associated secondary injuries that evolve through a cascade of pathological mechanisms. We aim at assessing how myelin and oligodendrocytes react to head angular-acceleration-induced TBI in a previously described model. This model induces axonal injuries visible by amyloid precursor protein (APP) expression, predominantly in the corpus callosum and its borders. Brain tissue from a total of 27 adult rats was collected at 24 h, 72 h and 7 d post-injury. Coronal sections were prepared for immunohistochemistry and RNAscope(R) to investigate DAI and myelin changes (APP, MBP, Rip), oligodendrocyte lineage cell loss (Olig2), oligodendrocyte progenitor cells (OPCs) (NG2, PDGFRa) and neuronal stress (HSP70, ATF3). Oligodendrocytes and OPCs numbers (expressed as percentage of positive cells out of total number of cells) were measured in areas with high APP expression. Results showed non-statistically significant trends with a decrease in oligodendrocyte lineage cells and an increase in OPCs. Levels of myelination were mostly unaltered, although Rip expression differed significantly between sham and injured animals in the frontal brain. Neuronal stress markers were induced at the dorsal cortex and habenular nuclei. We conclude that rotational injury induces DAI and neuronal stress in specific areas. We noticed indications of oligodendrocyte death and regeneration without statistically significant changes at the timepoints measured, despite indications of axonal injuries and neuronal stress. This might suggest that oligodendrocytes are robust enough to withstand this kind of trauma, knowledge important for the understanding of thresholds for cell injury and post-traumatic recovery potential.
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| 18. |
- Mazumder, Atiqul Haq, et al.
(författare)
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Reaction time and visual memory in connection to alcohol use in persons with bipolar disorder
- 2021
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to explore the association of cognition with hazardous drinking and alcohol-related disorder in persons with bipolar disorder (BD). The study population included 1268 persons from Finland with bipolar disorder. Alcohol use was assessed through hazardous drinking and alcohol-related disorder including alcohol use disorder (AUD). Hazardous drinking was screened with the Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) screening tool. Alcohol-related disorder diagnoses were obtained from the national registrar data. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on A tablet computer: the 5-choice serial reaction time task, or reaction time (RT) test and the Paired Associative Learning (PAL) test. Depressive symptoms were assessed with the Mental Health Inventory with five items (MHI-5). However, no assessment of current manic symptoms was available. Association between RT-test and alcohol use was analyzed with log-linear regression, and eβ with 95% confidence intervals (CI) are reported. PAL first trial memory score was analyzed with linear regression, and β with 95% CI are reported. PAL total errors adjusted was analyzed with logistic regression and odds ratios (OR) with 95% CI are reported. After adjustment of age, education, housing status and depression, hazardous drinking was associated with lower median and less variable RT in females while AUD was associated with a poorer PAL test performance in terms of the total errors adjusted scores in females. Our findings of positive associations between alcohol use and cognition in persons with bipolar disorder are difficult to explain because of the methodological flaw of not being able to separately assess only participants in euthymic phase.
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| 19. |
- Mazumder, Atiqul Haq, et al.
(författare)
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Reaction time and visual memory in connection to hazardous drinking polygenic scores in schizophrenia, schizoaffective and bipolar disorder
- 2021
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to explore the association of cognition with hazardous drinking Polygenic Scores (PGS) in 2649 schizophrenia, 558 schizoaffective disorder, and 1125 bipolar disorder patients in Finland. Hazardous drinking PGS was computed using the LDPred program. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on a tablet computer: the 5-choice serial reaction time task, or Reaction Time (RT) test, and the Paired Associative Learning (PAL) test. The association between hazardous drinking PGS and cognition was measured using four cognition variables. Log-linear regression was used in Reaction Time (RT) assessment, and logistic regression was used in PAL assessment. All analyses were conducted separately for males and females. After adjustment of age, age of onset, education, household pattern, and depressive symptoms, hazardous drinking PGS was not associated with reaction time or visual memory in male or female patients with schizophrenia, schizoaffective, and bipolar disorder.
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| 20. |
- Mazumder, Atiqul Haq, et al.
(författare)
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Reaction time and visual memory in connection with alcohol use in schizophrenia and schizoaffective disorder
- 2021
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to explore the association between cognition and hazardous drinking and alcohol use disorder in schizophrenia and schizoaffective disorder. Cognition is more or less compromised in schizophrenia, and schizoaffective disorder and alcohol use might aggravate this phenomenon. The study population included 3362 individuals from Finland with diagnoses of schizophrenia or schizoaffective disorder. Hazardous drinking was screened with the AUDIT-C (Alcohol Use Disorders Identification Test for Consumption) screening tool. Alcohol use disorder (AUD) diagnoses were obtained from national registrar data. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on a tablet computer: The Five-Choice Serial Reaction Time Task (5-CSRTT) or the reaction time (RT) test and the Paired Associative Learning (PAL) test. The association between alcohol use and the RT and PAL tests was analyzed with log-linear regression and logistic regression, respectively. After adjustment for age, education, housing status, and the age at which the respondents had their first psychotic episodes, hazardous drinking was associated with a lower median RT in females and less variable RT in males, while AUD was associated with a poorer PAL test performance in terms of the total errors adjusted scores (TEASs) in females. Our findings of positive associations between alcohol and cognition in schizophrenia and schizoaffective disorder are unique.
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| 21. |
- Mishra, S, et al.
(författare)
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Neurophysiological Correlates of Cognition as Revealed by Virtual Reality: Delving the Brain with a Synergistic Approach
- 2021
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The synergy of perceptual psychology, technology, and neuroscience can be used to comprehend how virtual reality affects cognition of human brain. Numerous studies have used neuroimaging modalities to assess the cognitive state and response of the brain with various external stimulations. The virtual reality-based devices are well known to incur visual, auditory, and haptic induced perceptions. Neurophysiological recordings together with virtual stimulations can assist in correlating humans’ physiological perception with response in the environment designed virtually. The effective combination of these two has been utilized to study human behavior, spatial navigation performance, and spatial presence, to name a few. Moreover, virtual reality-based devices can be evaluated for the neurophysiological correlates of cognition through neurophysiological recordings. Challenges exist in the integration of real-time neuronal signals with virtual reality-based devices, and enhancing the experience together with real-time feedback and control through neuronal signals. This article provides an overview of neurophysiological correlates of cognition as revealed by virtual reality experience, together with a description of perception and virtual reality-based neuromodulation, various applications, and existing challenges in this field of research.
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| 22. |
- Moller, ML, et al.
(författare)
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Improving Visual Function after Mild Traumatic Brain Injury Using a Vision Therapy Program: Case Reports
- 2020
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 10:12
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This case report describes the outcome of vision therapy for three patients who were referred to therapy due to visual symptoms after mild traumatic brain injury (MTBI). The criterion for inclusion was a high score (>21p) on the Convergence Insufficiency Symptom Survey (CISS) scale. The vision therapy program (VTP) included both face-to-face sessions and home-based tasks. Cases #1 and #2 had a substantial CISS scale evaluation improvement, and case #2 normalized the CISS scale score from 36 to 19. All patients agreed that vision therapy helped them understand their own vision and changes in their vision, which helped their overall recovery after MTBI. Rehabilitation professionals have an important role in screening for vision impairments and treating functional vision challenges after mild traumatic brain injury.
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| 23. |
- Moulin, Thiago, et al.
(författare)
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Transient Administration of Dopaminergic Precursor Causes Inheritable Overfeeding Behavior in Young Drosophila melanogaster Adults
- 2020
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Imbalances in dopaminergic signaling during development have been indicated as part of the underlying neurobiology of several psychiatric illnesses, including schizophrenia, major depression, bipolar disorder, and food addiction. Yet, how transient manipulation of dopaminergic signaling influences long-lasting behavioral consequences, or if these modifications can induce inheritable traits, it is still not understood. In this study, we used theDrosophila melanogastermodel to test if transient pharmacological activation of the dopaminergic system leads to modulations of feeding and locomotion in adult flies. We observed that transient administration of a dopaminergic precursor, levodopa, at 6 h, 3 days or 5 days post-eclosion, induced overfeeding behavior, while we did not find significant effects on locomotion. Moreover, this phenotype was inherited by the offspring of flies treated 6 h or 3 days post-eclosion, but not the offspring of those treated 5 days post-eclosion. These results indicate that transient alterations in dopaminergic signaling can produce behavioral alterations in adults, which can then be carried to descendants. These findings provide novel insights into the conditions in which environmental factors can produce transgenerational eating disorders.
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| 24. |
- Mårtensson, Johan, et al.
(författare)
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Structural changes on mri demonstrate specific cerebellar involvement in sle patients—a vbm study
- 2021
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Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to investigate possible differences in brain structure, as measured by T1-weighted MRI, between patients with systemic lupus erythematosus (SLE) and healthy controls (HC), and whether any observed differences were in turn more severe in SLE patients with neuropsychiatric manifestations (NPSLE) than those without (non-NPSLE). Structural T1weighted MRI was performed on 69 female SLE patients (mean age = 35.8 years, range = 18–51 years) and 24 age-matched female HC (mean age = 36.8 years, range = 23–52 years) in conjunction with neuropsychological assessment using the CNS Vital Signs test battery. T1-weighted images were preprocessed and analyzed by FSL-VBM. The results show that SLE patients had lower grey matter probability values than the control group in the VIIIa of the cerebellum bilaterally, a region that has previously been implied in sensorimotor processing in human and non-human primates. No structural differences for this region were found between NPSLE and non-NPSLE patients. VBM values from the VIIIa region showed a weak positive correlation with the psychomotor speed domain from CNS Vital Signs (p = 0.05, r = 0.21), which is in line with its presumed role as a sensorimotor processing area.
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| 25. |
- Nalvarte, I
(författare)
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Sex Stratified Treatment of Neurological Disorders: Challenges and Perspectives
- 2020
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 10:2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Despite the obvious sex differences in many of the most common neuropsychiatric and neurodegenerative disorders, males and females are still often treated the same from a clinical perspective. Why is that? The simple answer is that there is still too little known about this very complex matter. Sex hormone signaling, genetic sex, sex-biased comorbidities, and social gender perceptions all interact, making discrimination between the impacts of each of these factors hard to evaluate. Adding to the complexity is that important species differences must be taken into account when interpreting data from animal models. Clearly, to overcome this, larger efforts are needed that incorporate epidemiological, experimental, and clinical data to provide a solid scientific base for more personalized and informed clinical decisions that will benefit both men and women suffering from neurological disorders.
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| 26. |
- Olofsgard, FJ, et al.
(författare)
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PER Gene Family Polymorphisms in Relation to Cluster Headache and Circadian Rhythm in Sweden
- 2021
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- The trigeminal autonomic cephalalgia, cluster headache (CH), is one of the most painful disorders known to man. One of the disorder’s most striking features is the reported diurnal rhythmicity of the attacks. For a majority of patients, the headache attacks occur at approximately the same time every day. Genetic variants of genes involved in the circadian rhythm such as Period Circadian Regulator 1, 2, and 3 (PER1, 2 and 3) are hypothesized to have an effect on the rhythmicity of the attacks. Six PER1, 2 and 3 genetic markers; the indel rs57875989 and five single nucleotide polymorphisms (SNPs), rs2735611, rs2304672, rs934945, rs10462020, and rs228697, were genotyped, using TaqMan® or regular polymerase chain reaction (PCR), in a Swedish CH case control material. Logistic regression showed no association between CH and any of the six genetic variants; rs57875989, p = 0.523; rs2735611, p = 0.416; rs2304672, p = 0.732; rs934945, p = 0.907; rs10462020, p = 0.726; and rs228697, p = 0.717. Furthermore, no difference in allele frequency was found for patients reporting diurnal rhythmicity of attacks, nor were any of the variants linked to diurnal preference. The results of this study indicate no involvement of these PER genetic variants in CH or diurnal phenotype in Sweden.
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| 27. |
- Peteri, Ulla Kaisa, et al.
(författare)
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Generation of the human pluripotent stem-cell-derived astrocyte model with forebrain identity
- 2021
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Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytes form functionally and morphologically distinct populations of cells with brain-region-specific properties. Human pluripotent stem cells (hPSCs) offer possibilities to generate astroglia for studies investigating mechanisms governing the emergence of astrocytic diversity. We established a method to generate human astrocytes from hPSCs with forebrain patterning and final specification with ciliary neurotrophic factor (CNTF). Transcriptome profiling and gene enrichment analysis monitored the sequential expression of genes determining astrocyte differentiation and confirmed activation of forebrain differentiation pathways at Day 30 (D30) and D60 of differentiation in vitro. More than 90% of astrocytes aged D95 in vitro co-expressed the astrocytic markers glial fibrillary acidic protein (GFAP) and S100β. Intracellular calcium responses to ATP indicated differentiation of the functional astrocyte population with constitutive monocyte chemoattractant protein-1 (MCP-1/CCL2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) expression. The method was reproducible across several hPSC lines, and the data demonstrated the usefulness of forebrain astrocyte modeling in research investigating forebrain pathology.
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| 28. |
- Ran, CE, et al.
(författare)
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Analysis of NOS Gene Polymorphisms in Relation to Cluster Headache and Predisposing Factors in Sweden
- 2021
-
Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Cluster headache is characterized by activation of the autonomic-trigeminal reflex. Nitric oxide can trigger headaches in patients, and nitric oxide signaling is known to be affected in cluster headache. Based on the hypothesis of nitric oxide being involved in cluster headache pathophysiology we investigated nitric oxide synthases as potential candidate genes for cluster headache. We analyzed eight variants in the three forms of nitric oxide synthase (NOS) genes, inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS), and tested for association with cluster headache. Swedish cluster headache patients (n = 542) and controls (n = 581) were genotyped using TaqMan® assays on an Applied Biosystems 7500 qPCR cycler. This is the largest performed genetic study on NOS involvement in cluster headache so far. We found an association between cluster headache and one iNOS haplotype consisting of the minor alleles of rs2297518 and rs2779249 (p = 0.022). In addition, one of the analyzed nNOS variants, rs2682826, was associated with reported triptan use (p = 0.039). Our data suggest that genetic variants in NOS genes do not have a strong influence on cluster headache pathophysiology, but that certain combinations of genetic variants in NOS genes may influence the risk of developing the disorder or triptan use.
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| 29. |
- Ran, C, et al.
(författare)
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Anoctamin 3: A Possible Link between Cluster Headache and Ca2+ Signaling
- 2019
-
Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Cluster headache is a severe primary headache characterized by extremely painful attacks of unilateral headache. Verapamil is commonly used as a prophylactic treatment with good effect. In order to search for new pathways involved in the pathophysiology of cluster headache, we analyzed genetic variants that were previously linked to verapamil response in migraine in a Swedish cluster headache case-control sample. We used TaqMan qPCR for genetic screening and performed a gene expression analysis on associated genes in patient-derived fibroblasts, and further investigated which reference genes were suitable for analysis in fibroblasts from cluster headache patients. We discovered a significant association between anoctamin 3, a gene encoding a calcium-activated ion channel, and cluster headache. The association was not dependent on verapamil treatment since the associated variant, rs1531394, was also overrepresented in patients not using verapamil. No difference was found in the anoctamin 3 gene expression between controls and patients. Also, we determined that TBP, IPO8 and PDHB were suitable reference genes in cluster headache fibroblasts. This finding is the first report of an association between a variant in a gene encoding an ion-channel and cluster headache, and the first significant genetic evidence of calcium involvement in cluster headache pathophysiology.
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| 30. |
- Rasa-Dzelzkaleja, S, et al.
(författare)
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Persistent Roseoloviruses Infection in Adult Patients with Epilepsy
- 2020
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Human herpesviruses (HHV)-6A, HHV-6B and HHV-7 are considered to be involved in the pathogenesis of epilepsy, a common neurological disorder. The objective of this study was to determine the association of roseoloviruses infection with epilepsy. Methods: 53 epilepsy patients and 104 ordinary blood donors were analyzed to determine presence of virus-specific antibodies by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA), genomic sequences, viral load and gene expression by polymerase chain reactions (PCRs) and restriction analysis, HHV-6 protein expression by IFA and level of cytokines by ELISA. Results: Roseoloviruses genomic sequences in DNA samples from whole blood were found in 86.8% of patients versus 54.8% of controls and active infection was revealed only in patients with epilepsy (19.6% of roseolovirus-positive patients). Significantly higher viral load and more frequent gene expression was detected in patients compared to the controls. HHV-6-encoded protein expression was demonstrated in 53.3% of patients with previously detected HHV-6 DNA. Changes in level of cytokines were determined in patients with elevated viral load compared to the patients without elevated viral loads and to the controls. Conclusions: Results on frequent active HHV-6 and HHV-7 infection in epilepsy patient’ peripheral blood indicate on possible involvement of these viruses in the disease development.
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| 31. |
- Rosqvist, Kristina, et al.
(författare)
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Caregiver Burden and Quality of Life in Late Stage Parkinson’s Disease
- 2022
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Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Parkinson’s disease (PD) is a chronic, progressive, neurodegenerative disease involving both motor and non-motor symptoms (NMS). In the late stage of the disease, Hoehn and Yahr (HY) stages IV-V, the symptomatology is often severe and patients become increasingly dependent on help in their daily life, resulting in an increased burden for the informal caregivers. To assess the implications of the caregiver burden, caregiver quality of life (QoL) was assessed in 74 informal caregivers to patients in late stage PD, by the Alzheimer’s Patient Partners Life Impact Questionnaire (APPLIQue), which has been found useful also in PD. The majority of caregivers were the spouse/partner. Individual items provided information on which aspects of caregiver burden were the most common, i.e., items: “feel guilty if not there” (71% affirmed), “situation wears me down” (65% affirmed) and “always on my mind” (61% affirmed). In simple linear regression analyses, female patient gender (p = 0.007), better cognition (p = 0.004), lower NMS burden (p = 0.012) and not being the partner (p = 0.022) were associated with better caregiver QoL. Multivariable linear regression analyses identified better cognition (p = 0.004) and female patient gender (p = 0.035) as independently associated with better informal caregiver QoL. Identifying and treating NMS as well as recognizing and alleviating caregiver burden seem essential to enhance QoL for both patients and caregivers in late stage PD.
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| 32. |
- Saldert, Charlotta, 1966, et al.
(författare)
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Multifaceted communication problems in everyday conversations involving people with Parkinson’s Disease
- 2017
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Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- It is known that Parkinson’s disease is often accompanied by a motor speech disorder, which results in impaired communication. However, people with Parkinson’s disease may also have impaired word retrieval (anomia) and other communicative problems, which have a negative impact on their ability to participate in conversations with family as well as healthcare staff. The aim of the present study was to explore effects of impaired speech and language on communication and how this is managed by people with Parkinson’s disease and their spouses. Using a qualitative method based on Conversation Analysis, in-depth analyses were performed on natural conversational interaction in five dyads including elderly men who were at different stages of Parkinson’s disease. The findings showed that the motor speech disorder in combination with word retrieval difficulties and adaptations, such as using communication strategies, may result in atypical utterances that are difficult for communication partners to understand. The coexistence of several communication problems compounds the difficulties faced in conversations and individuals with Parkinson’s disease are often dependent on cooperation with their communication partner to make themselves understood.
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| 33. |
- Shell, Amy, et al.
(författare)
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The Link between Attachment Style and Self-Reported Olfactory Ability : A Preliminary Investigation
- 2021
-
Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 11:10
-
Tidskriftsartikel (refereegranskat)abstract
- Individuals in healthy romantic relationships gain significant benefits to their psychological wellbeing and physiological health. Notably, the majority of relationship research has focused on how adult attachment influences these relationship outcomes while the role of olfaction remains an emerging research focus. The aim of the current study was to bring together these seemingly unrelated factors–attachment and olfaction–in an online quasi-experimental design. The participants were 401 undergraduate students, predominantly females, ranging in age from 17 to 70 years. Participants completed a battery of questionnaires that evaluated their attachment tendencies, olfactory ability and experiences in romantic relationships. Results indicated that attachment insecurity, across both attachment anxiety and avoidance, was associated with decreased olfactory functioning for females. These findings provide preliminary evidence that olfaction is related to romantic relationship maintenance and suggests that body odors could be fundamental for evoking the attachment system. These findings also elicit enticing new avenues of research which can assist psychologists to provide targeted treatments to individuals with olfactory deficits and insecure attachment tendencies.
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| 34. |
- Smailovic, Una, et al.
(författare)
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Decreased Global EEG Synchronization in Amyloid Positive Mild Cognitive Impairment and Alzheimer’s Disease Patients—Relationship to APOE ε4
- 2021
-
Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 11:10
-
Tidskriftsartikel (refereegranskat)abstract
- The apolipoprotein E (APOE) ε4 allele is a risk factor for Alzheimer’s disease (AD) that has been linked to changes in brain structure and function as well as to different biological subtypes of the disease. The present study aimed to investigate the association of APOE ε4 genotypes with brain functional impairment, as assessed by quantitative EEG (qEEG) in patients on the AD continuum. The study population included 101 amyloid positive patients diagnosed with mild cognitive impairment (MCI) (n = 50) and AD (n = 51) that underwent resting-state EEG recording and CSF Aβ42 analysis. In total, 31 patients were APOE ε4 non-carriers, 42 were carriers of one, and 28 were carriers of two APOE ε4 alleles. Quantitative EEG analysis included computation of the global field power (GFP) and global field synchronization (GFS) in conventional frequency bands. Amyloid positive patients who were carriers of APOE ε4 allele(s) had significantly higher GFP beta and significantly lower GFS in theta and beta bands compared to APOE ε4 non-carriers. Increased global EEG power in beta band in APOE ε4 carriers may represent a brain functional compensatory mechanism that offsets global EEG slowing in AD patients. Our findings suggest that decreased EEG measures of global synchronization in theta and beta bands reflect brain functional deficits related to the APOE ε4 genotype in patients that are on a biomarker-verified AD continuum.
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| 35. |
- Smedfors, G, et al.
(författare)
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Genetic Screening of Plasticity Regulating Nogo-Type Signaling Genes in Migraine
- 2020
-
Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Migraine is the sixth most prevalent disease in the world and a substantial number of experiments have been conducted to analyze potential differences between the migraine brain and the healthy brain. Results from these investigations point to the possibility that development and aggravation of migraine may include grey matter plasticity. Nogo-type signaling is a potent plasticity regulating system in the CNS and consists of ligands, receptors, co-receptors and modulators with a dynamic age- and activity-related expression in cortical and subcortical regions. Here we investigated a potential link between migraine and five key Nogo-type signaling genes: RTN4, OMGP, MAG, RTN4R and LINGO1, by screening 15 single nucleotide polymorphisms (SNPs) within these genes. In a large Swedish migraine cohort (749 migraine patients and 4032 controls), using a logistic regression with sex as covariate, we found that there was no such association. In addition, a haplotype analysis was performed which revealed three haplotype blocks. These blocks had no significant association with migraine. However, to robustly conclude that Nogo-type genotypes signaling do not influence the prevalence of migraine, further studies are encouraged.
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| 36. |
- Srinivas, NS, et al.
(författare)
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An Overview on Cognitive Function Enhancement through Physical Exercises
- 2021
-
Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 11:10
-
Tidskriftsartikel (refereegranskat)abstract
- This review is extensively focused on the enhancement of cognitive functions while performing physical exercises categorized into cardiovascular exercises, resistance training, martial arts, racquet sports, dancing and mind-body exercises. Imaging modalities, viz. functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), have been included in this review. This review indicates that differences are present in cognitive functioning while changing the type of physical activity performed. This study concludes that employing fNIRS helps overcome certain limitations of fMRI. Further, the effects of physical activity on a diverse variety of the population, from active children to the old people, are discussed.
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| 37. |
- Svennigsen, Åsa Fex, et al.
(författare)
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Repair of the peripheral nerve-remyelination that works
- 2013
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Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 3:3, s. 1182-1197
-
Forskningsöversikt (refereegranskat)abstract
- In this review we summarize the events known to occur after an injury in the peripheral nervous system. We have focused on the Schwann cells, as they are the most important cells for the repair process and facilitate axonal outgrowth. The environment created by this cell type is essential for the outcome of the repair process. The review starts with a description of the current state of knowledge about the initial events after injury, followed by Wallerian degeneration, and subsequent regeneration. The importance of surgical repair, carried out as soon as possible to increase the chances of a good outcome, is emphasized throughout the review. The review concludes by describing the target re-innervation, which today is one of the most serious problems for nerve regeneration. It is clear, compiling this data, that even though regeneration of the peripheral nervous system is possible, more research in this area is needed in order to perfect the outcome.
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| 38. |
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| 39. |
- Vega-Mendoza, Mariana, et al.
(författare)
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Testing the Foreign Language Effect on Cognitive Reflection in Older Adults
- 2021
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 11:11
-
Tidskriftsartikel (refereegranskat)abstract
- An increasing number of people around the world communicate in more than one language, resulting in them having to make decisions in a foreign language on a daily basis. Interestingly, a burgeoning body of literature suggests that people’s decision-making is affected by whether they are reasoning in their native language (NL) or their foreign language (FL). According to the foreign language effect (FLe), people are less susceptible to bias in many decision-making tasks and more likely to display utilitarian cost-benefit analysis in moral decision-making when reasoning in a FL. While these differences have often been attributed to a reduced emotionality in the FL, an emerging body of literature has started to test the extent to which these could be attributable to increased deliberation in the FL. The present study tests whether increased deliberation leads to a FLe on cognitive reflection in a population of older adults (Mage = 65.1), from the successful aging project in Umeå, Sweden. We explored whether performance on a 6-item version of the cognitive reflection test (CRT) adapted to Swedish would differ between participants for whom Swedish was their NL and those for whom Swedish was their FL. The CRT is a task designed to elicit an incorrect, intuitive answer. In order to override the intuitive answer, one requires engaging in deliberative, analytical thinking to determine the correct answer. Therefore, we hypothesized that if thinking in a FL increases deliberation, then those performing the task in their FL would exhibit higher accuracy rates than those performing in their NL. Our results showed that age and level of education predicted performance on the task but performance on the CRT did not differ between the NL and the FL groups. In addition, in the FL group, proficiency in the FL was not related to performance in the CRT. Our results, therefore, do not provide evidence that thinking in a FL increases deliberation in a group of older adults performing a logical reasoning task that is not typically associated with an emotional connotation.
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| 40. |
- Vismara, M, et al.
(författare)
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Peripheral Biomarkers in DSM-5 Anxiety Disorders: An Updated Overview
- 2020
-
Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 10:8
-
Tidskriftsartikel (refereegranskat)abstract
- Anxiety disorders are prevalent and highly disabling mental disorders. In recent years, intensive efforts focused on the search for potential neuroimaging, genetic, and peripheral biomarkers in order to better understand the pathophysiology of these disorders, support their diagnosis, and characterize the treatment response. Of note, peripheral blood biomarkers, as surrogates for the central nervous system, represent a promising instrument to characterize psychiatric disorders, although their role has not been extensively applied to clinical practice. In this report, the state of the art on peripheral biomarkers of DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) Anxiety Disorders is presented, in order to examine their role in the pathogenesis of these conditions and their potential application for diagnosis and treatment. Available data on the cerebrospinal fluid and blood-based biomarkers related to neurotransmitters, neuropeptides, the hypothalamic–pituitary–adrenal axis, neurotrophic factors, and the inflammation and immune system are reviewed. Despite the wide scientific literature and the promising results in the field, only a few of the proposed peripheral biomarkers have been defined as a specific diagnostic instrument or have been identified as a guide in the treatment response to DSM-5 Anxiety Disorders. Therefore, further investigations are needed to provide new biological insights into the pathogenesis of anxiety disorders, to help in their diagnosis, and to tailor a treatment.
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| 41. |
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| 42. |
- Aspli, Klaus Thanke, et al.
(författare)
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CSF, Blood, and MRI Biomarkers in Skogholt’s Disease - A Rare Neurodegenerative Disease in a Norwegian Kindred
- 2023
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Ingår i: Brain Sciences. - 2076-3425. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Skogholt’s disease is a rare neurological disorder that is only observed in a small Norwegian kindred. It typically manifests in adulthood with uncharacteristic neurological symptoms from both the peripheral and central nervous systems. The etiology of the observed cerebral white matter lesions and peripheral myelin pathology is unclear. Increased cerebrospinal fluid (CSF) concentrations of protein have been confirmed, and recently, very high concentrations of CSF total and phosphorylated tau have been detected in Skogholt patients. The symptoms and observed biomarker changes in Skogholt’s disease are largely nonspecific, and further studies are necessary to elucidate the disease mechanisms. Here, we report the results of neurochemical analyses of plasma and CSF, as well as results from the morphometric segmentation of cerebral magnetic resonance imaging. We analyzed the biomarkers Aβ1––42, Aβ1–40, Aβx–38, Aβx–40, Aβx–42, total and phosphorylated tau, glial fibrillary acidic protein, neurofilament light chain, platelet-derived growth factor receptor beta, and beta-trace protein. All analyzed CSF biomarkers, except neurofilament light chain and Aβ1/x–42, were increased several-fold. In blood, none of these biomarkers were significantly different between the Skogholt and control groups. MRI volumetric segmentation revealed decreases in the ventricular, white matter, and choroid plexus volumes in the Skogholt group, with an accompanying increase in white matter lesions. The cortical thickness and subcortical gray matter volumes were increased in the Skogholt group. Pathophysiological changes resulting from choroidal dysfunction and/or abnormal CSF turnover, which may cause the increases in CSF protein and brain biomarker levels, are discussed.
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| 43. |
- Balter, Leonie J. T., et al.
(författare)
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Experimental Sleep Deprivation Results in Diminished Perceptual Stability Independently of Psychosis Proneness
- 2022
-
Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 12:10
-
Tidskriftsartikel (refereegranskat)abstract
- Psychotic disorders as well as psychosis proneness in the general population have been associated with perceptual instability, suggesting weakened predictive processing. Sleep disturbances play a prominent role in psychosis and schizophrenia, but it is unclear whether perceptual stability diminishes with sleep deprivation, and whether the effects of sleep deprivation differ as a function of psychosis proneness. In the current study, we aimed to clarify this matter. In this preregistered study, 146 participants successfully completed an intermittent version of the random dot kinematogram (RDK) task and the 21-item Peters Delusion Inventory (PDI-21) to assess perceptual stability and psychosis proneness, respectively. Participants were randomized to sleep either as normal (8 to 9 h in bed) (n = 72; Mage = 24.7, SD = 6.2, 41 women) or to stay awake through the night (n = 74; Mage = 24.8, SD = 5.1, 44 women). Sleep deprivation resulted in diminished perceptual stability, as well as in decreases in perceptual stability over the course of the task. However, we did not observe any association between perceptual stability and PDI-21 scores, nor a tendency for individuals with higher PDI-21 scores to be more vulnerable to sleep-deprivation-induced decreases in perceptual stability. The present study suggests a compromised predictive processing system in the brain after sleep deprivation, but variation in psychosis trait is not related to greater vulnerability to sleep deprivation in our dataset. Further studies in risk groups and patients with psychosis are needed to evaluate whether sleep loss plays a role in the occurrence of objectively measured perceptual-related clinical symptoms.
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| 44. |
- Bencze, J, et al.
(författare)
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Lemur Tyrosine Kinase 2 (LMTK2) Level Inversely Correlates with Phospho-Tau in Neuropathological Stages of Alzheimer's Disease
- 2020
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is the most common neurodegenerative dementia. Mapping the pathomechanism and providing novel therapeutic options have paramount significance. Recent studies have proposed the role of LMTK2 in AD. However, its expression pattern and association with the pathognomonic neurofibrillary tangles (NFTs) in different brain regions and neuropathological stages of AD is not clear. We performed chromogenic (CHR) LMTK2 and fluorescent phospho-tau/LMTK2 double-labelling (FDL) immunohistochemistry (IHC) on 10–10 postmortem middle frontal gyrus (MFG) and anterior hippocampus (aHPC) samples with early and late neuropathological Braak tau stages of AD. MFG in early stage was our ‘endogenous control’ region as it is not affected by NFTs. Semiquantitative CHR-IHC intensity scoring revealed significantly higher (p < 0.001) LMTK2 values in this group compared to NFT-affected regions. FDL-IHC demonstrated LMTK2 predominance in the endogenous control region, while phospho-tau overburden and decreased LMTK2 immunolabelling were detected in NFT-affected groups (aHPC in early and both regions in late stage). Spearman’s correlation coefficient showed strong negative correlation between phospho-tau/LMTK2 signals within each group. According to our results, LMTK2 expression is inversely proportionate to the extent of NFT pathology, and decreased LMTK2 level is not a general feature in AD brain, rather it is characteristic of the NFT-affected regions.
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| 45. |
- Beukes, Eldre W, et al.
(författare)
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Experiential Characteristics among Individuals with Tinnitus Seeking Online Psychological Interventions : A Cluster Analysis
- 2022
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study was designed to gain insights regarding patterns of social representations (values, ideas, beliefs) of tinnitus and their relation to demographic and clinical factors.METHOD: A cross-sectional survey design was used including 399 adults seeking help and reporting interest in internet-based cognitive behavior therapy for tinnitus. Data were collected using a free association task and analysis used qualitative (content analysis) and quantitative (cluster analysis and chi-square analysis) using the Iramuteq software.RESULTS: The social representations identified the negative impact of tinnitus and included the way it sounded (descriptions of the way tinnitus sounds (18%), annoyance (13.5%), and persistence (8%)). Four clusters were identified representing four levels of tinnitus severity, namely debilitating tinnitus (24%), distressing tinnitus (10%), annoying tinnitus (46%), and accepting tinnitus (20%). Cluster identity was associated with demographic and clinical variables.DISCUSSION: The identified clusters represented tinnitus severity experience in four stages, ranging from debilitating tinnitus to acceptance of tinnitus. These findings are important for clinical practice where tinnitus descriptions can indicate the stage of the tinnitus experience and which intervention pathway may be most appropriate.
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| 46. |
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| 47. |
- Cannito, L, et al.
(författare)
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The Role of Stress and Cognitive Absorption in Predicting Social Network Addiction
- 2022
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Nowadays, the use of social networks (SNs) is pervasive and ubiquitous. Among other things, SNs have become a key resource for establishing and maintaining personal relationships, as further demonstrated by the emergence of the pandemic. However, easy access to SNs may be a source of addictive behaviour, especially among the younger population. The literature highlights various psychological and physiological factors as possible predictors of vulnerability to SN addiction. This paper explores the joint effects of stress level and cognitive absorption, in the form of temporal dissociation while on SNs, on the addiction of university students to SNs. Here, 312 participants were involved in an online survey. About 14% of the sample presented a risk for SN addiction. Moreover, it was found that stress level predicted SN addiction both directly and indirectly through the effect of individual temporal dissociation, as experienced during SN usage. These results suggest a significant role of perceived stress level on addiction risk, while also pointing out additional vulnerability to SN addiction for cognitive profiles that are relatively more prone to temporal dissociation while online.
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| 48. |
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| 49. |
- Chahla, MA, et al.
(författare)
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Biological Factors Underpinning Suicidal Behaviour: An Update
- 2023
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Suicide, a global health burden, represents the 17th leading cause of death worldwide (1.3%), but the 4th among young people aged between 15 and 29 years of age, according to World Health Organization (WHO), 2019. Suicidal behaviour is a complex, multi-factorial, polygenic and independent mental health problem caused by a combination of alterations and dysfunctions of several biological pathways and disruption of normal mechanisms in brain regions that remain poorly understood and need further investigation to be deciphered. Suicide complexity and unpredictability gained international interest as a field of research. Several studies have been conducted at the neuropathological, inflammatory, genetic, and molecular levels to uncover the triggers behind suicidal behaviour and develop convenient and effective therapeutic or at least preventive procedures. This review aims to summarise and focus on current knowledge of diverse biological pathways involved in the neurobiology of suicidal behaviour, and briefly highlights future potential therapeutic pathways to prevent or even treat this significant public health problem.
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| 50. |
- De Rosa, Oreste, et al.
(författare)
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Habitual Videogame Playing Does Not Compromise Subjective Sleep Quality and Is Associated with Improved Daytime Functioning
- 2023
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Research on the effects of videogames (VGs) on health has produced mixed results. Here, we assess the relationships of VG playing with sleep; chronotype; sleepiness; and levels of depression, anxiety, and stress; and how they are modulated by the level of exposure to VGs. Four hundred-and two adult participants (age = 26.2 +/- 7.84; 227 F) completed an online survey including questions on VG use and a set of standardized questionnaires. The sample was divided into three groups: habitual gamers (HGs, 42.2%), nonhabitual gamers (NHGs, 36.5%), and non-gamers (NGs, 21.3%). No between-group differences emerged in sleepiness (Epworth Sleepiness Scale) or Pittsburgh Sleep Quality Index measures except the sleep disturbances subscore, which was higher in NHGs. HGs showed delayed bed- and risetimes and higher eveningness (reduced Morningness-Eveningness Questionnaire). HGs and NHGs showed higher depression subscores (Depression Anxiety Stress Scale) but remained in the subclinical range. Moreover, hours/week of VG playing predicted delayed sleep timing, lower daytime dysfunction, and lower sleepiness. Our data suggest that VG playing does not necessarily compromise sleep quality and may even benefit daytime functioning, underlining the need to reconsider the relationships between VG use and health by taking into account possible modulating factors such as habitual VG exposure.
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