| 1. |
- Amat-Foraster, Maria, et al.
(författare)
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Modulation of thalamo-cortical activity by the NMDA receptor antagonists ketamine and phencyclidine in the awake freely-moving rat
- 2019
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Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 158
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Tidskriftsartikel (refereegranskat)abstract
- Non-competitive N-methyl-D-aspartate receptor antagonists mimic schizophrenia symptoms and produce immediate and persistent antidepressant effects. We investigated the effects of ketamine and phencyclidine (PCP) on thalamo-cortical network activity in awake, freely-moving male Wistar rats to gain new insight into the neuronal populations and brain circuits involved in the effects of NMDA-R antagonists. Single unit and local field potential (LFP) recordings were conducted in mediodorsal/centromedial thalamus and in medial prefrontal cortex (mPFC) using microelectrode arrays. Ketamine and PCP moderately increased the discharge rates of principal neurons in both areas while not attenuating the discharge of mPFC GABAergic interneurons. They also strongly affected LFP activity, reducing beta power and increasing that of gamma and high-frequency oscillation bands. These effects were short-lasting following the rapid pharmacokinetic profile of the drugs, and consequently were not present at 24 h after ketamine administration. The temporal profile of both drugs was remarkably different, with ketamine effects peaking earlier than PCP effects. Although this study is compatible with the glutamate hypothesis for fast-acting antidepressant action, it does not support a local disinhibition mechanism as the source for the increased pyramidal neuron activity in mPFC. The short-lasting increase in thalamo-cortical activity is likely associated with the rapid psychotomimetic action of both agents but could also be part of a cascade of events ultimately leading to the persistent antidepressant effects of ketamine. Changes in spectral contents of high-frequency bands by the drugs show potential as translational biomarkers for target engagement of NMDA-R modulators.
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| 2. |
- Behjat, Hamid, et al.
(författare)
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Signal-Adapted Tight Frames on Graphs
- 2016
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Ingår i: IEEE Transactions on Signal Processing. - 1053-587X. ; 64:22, s. 6017-6029
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Tidskriftsartikel (refereegranskat)abstract
- The analysis of signals on complex topologies modeled by graphs is a topic of increasing importance. Decompositions play a crucial role in the representation and processing of such information. Here, we propose a new tight frame design that is adapted to a class of signals on a graph. The construction starts from a prototype Meyer-type system of kernels with uniform subbands. The ensemble energy spectral density is then defined for a given set of signals defined on the graph. The prototype design is then warped such that the resulting subbands capture the same amount of energy for the signal class. This approach accounts at the same time for graph topology and signal features. The proposed frames are constructed for three different graph signal sets and are compared with non-signal-adapted frames. Vertex localization of a set of resulting atoms is studied. The frames are then used to decompose a set of real graph signals and are also used in a setting of signal denoising. The results illustrate the superiority of the designed signal-adapted frames, over frames blind to signal characteristics, in representing data and in denoising.
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| 3. |
- Belic, Jovana, 1987-, et al.
(författare)
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Behavior Discrimination Using a Discrete Wavelet Based Approach for Feature Extraction on Local Field Potentials in the Cortex and Striatum
- 2015
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Ingår i: 7th International IEEE/EMBS Conference on Neural Engineering (NER). - : IEEE conference proceedings. - 9781467363891 ; , s. 964-967
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Konferensbidrag (refereegranskat)abstract
- Linkage between behavioral states and neural activity is one of the most important challenges in neuroscience. The network activity patterns in the awake resting state and in the actively behaving state in rodents are not well understood, and a better tool for differentiating these states can provide insights on healthy brain functions and its alteration with disease. Therefore, we simultaneously recorded local field potentials (LFPs) bilaterally in motor cortex and striatum, and measured locomotion from healthy, freely behaving rats. Here we analyze spectral characteristics of the obtained signals and present an algorithm for automatic discrimination of the awake resting and the behavioral states. We used the Support Vector Machine (SVM) classifier and utilized features obtained by applying discrete wavelet transform (DWT) on LFPs, which arose as a solution with high accuracy.
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| 4. |
- Belic, Jovana, et al.
(författare)
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Corticostriatal circuits and their role in disease
- 2015
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Ingår i: Frontiers in Neuroscience. - Cairns, Australia : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 8, s. 31-
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Tidskriftsartikel (refereegranskat)abstract
- The basal ganglia (BG) represent subcortical structures considered to be involved in action selection and decision making [1]. Dysfunction of the BG circuitry leads to many motor and cognitive disorders such as Parkinson’s disease (PD), Tourette syndrome, Huntington’s disease, obsessive compulsive disorder and many others. Therefore, we simultaneously recorded local field potentials (LFPs) in primary motor cortex and sensorimotor striatum to study features directly related to healthy versus pathological states such as Parkinson disease and levodopa-induced dyskinesia [2], [3]. The striatum, the input stage of the basal ganglia (BG), is an inhibitory network that contains several distinct cell types and receives massive excitatory inputs from the cortex. Cortex sends direct projections to the striatum, while striatum can affect cortex only indirectly through other BG nuclei and thalamus. Firstly we analyzed spectral characteristics of the obtained signals and observed that during dyskinesia, the most prominent feature was a relative power increase in the high gamma frequency range around 80 Hz, while for PD it was the beta frequency range. Secondly our preliminary results have shown that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on striatal influence on cortex. In the case of dyskinesia we have also found a specifically high increase in effective connectivity at 80 Hz. In order to further understand the 80-Hz phenomenon we have performed cross-frequency analysis across all states and both structures and observed characteristic patterns in the case of dyskinesia in both structures but not in the case of PD and healthy state. We have seen a large relative decrease in the modulation of the amplitude at 80Hz by the phase of low frequency oscillations (up to ~10Hz). It has been suggested that the activity of local neural populations is modulated according to the global neuronal dynamics in the way that populations oscillate and synchronize at lower frequencies and smaller ensembles are active at higher frequencies Our results suggest unexpectedly a lack of coupling between the low frequency activity of a larger population and the synchronized activity of a smaller group of neurons active at 80Hz.
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| 5. |
- Belic, Jovana, 1987-, et al.
(författare)
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Untangling cortico-striatal connectivity and cross-frequency coupling in L-DOPA-induced dyskinesia
- 2016
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Ingår i: Frontiers in Systems Neuroscience. - : Frontiers. - 1662-5137. ; 10:26, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- We simultaneously recorded local field potentials in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats in order to study the features directly related to pathological states such as parkinsonian state and levodopa-induced dyskinesia. We analysed the spectral characteristics of the obtained signals and observed that during dyskinesia the most prominent feature was a relative power increase in the high gamma frequency range at around 80 Hz, while for the parkinsonian state it was in the beta frequency range. Here we show that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on the striatal influence on the cortex. In the case of dyskinesia, we also found a high increase in effective connectivity at 80 Hz. In order to further understand the 80- Hz phenomenon, we performed cross-frequency analysis and observed characteristic patterns in the case of dyskinesia but not in the case of the parkinsonian state or the healthy state. We noted a large decrease in the modulation of the amplitude at 80 Hz by the phase of low frequency oscillations (up to ~10 Hz) across both structures in the case of dyskinesia. This may suggest a lack of coupling between the low frequency activity of the recorded network and the group of neurons active at ~80 Hz.
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| 6. |
- Budczies, Jan, et al.
(författare)
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Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue - a GC-TOFMS based metabolomics study
- 2012
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS) is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far.RESULTS: A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468 metabolite peaks could be detected; out of these 368 (79%) were significantly changed between cancer and normal tissues (p<0.05 in training and validation set). Furthermore, 13 tumor and 7 normal tissue markers were identified that separated cancer from normal tissues with a sensitivity and a specificity of >80%. Two-metabolite classifiers, constructed as ratios of the tumor and normal tissues markers, separated cancer from normal tissues with high sensitivity and specificity. Specifically, the cytidine-5-monophosphate / pentadecanoic acid metabolic ratio was the most significant discriminator between cancer and normal tissues and allowed detection of cancer with a sensitivity of 94.8% and a specificity of 93.9%.CONCLUSIONS: For the first time, a comprehensive metabolic map of breast cancer was constructed by GC-TOF analysis of a large cohort of breast cancer and normal tissues. Furthermore, our results demonstrate that spectrometry-based approaches have the potential to contribute to the analysis of biopsies or clinical tissue samples complementary to histopathology.
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| 7. |
- Börjesson, Per Ola, et al.
(författare)
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Free-riding in Group Work - Mechanisms and Countermeasures
- 2006
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Ingår i: [Host publication title missing].
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Konferensbidrag (refereegranskat)abstract
- Studies have shown that group work offers great possibilities for deeper learning compared to some more traditional teaching formats [1], but it can also lead to some new problems such as free-riding. Different aspects of group psychology and behaviour as well as impropriate group sizes can be used to explain why and how free-riding develops in groups. With careful course planning teachers can seriously discourage students from free-riding. Especially the grading system should be carefully chosen not to promote free-riding but to stimulate deeper learning
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| 8. |
- de Jong, R. S., et al.
(författare)
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4MOST : Project overview and information for the First Call for Proposals
- 2019
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Ingår i: The Messenger. - : European Southern Observatory. - 0722-6691. ; 175, s. 3-11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We introduce the 4-metre Multi-Object Spectroscopic Telescope (4MOST), a new high-multiplex, wide-field spectroscopic survey facility under development for the four-metre-class Visible and Infrared Survey Telescope for Astronomy (VISTA) at Paranal. Its key specifications are: a large field of view (FoV) of 4.2 square degrees and a high multiplex capability, with 1624 fibres feeding two low-resolution spectrographs (R = λ/Δλ ~ 6500), and 812 fibres transferring light to the high-resolution spectrograph (R ~ 20 000). After a description of the instrument and its expected performance, a short overview is given of its operational scheme and planned 4MOST Consortium science; these aspects are covered in more detail in other articles in this edition of The Messenger. Finally, the processes, schedules, and policies concerning the selection of ESO Community Surveys are presented, commencing with a singular opportunity to submit Letters of Intent for Public Surveys during the first five years of 4MOST operations.
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| 9. |
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| 10. |
- Halje, Pär, et al.
(författare)
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Levodopa-induced dyskinesia is strongly associated with resonant cortical oscillations.
- 2012
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Ingår i: The Journal of Neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 32:47, s. 16541-16551
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Tidskriftsartikel (refereegranskat)abstract
- The standard pharmacological treatment for Parkinson's disease using the dopamine precursor levodopa is unfortunately limited by gradual development of disabling involuntary movements for which the underlying causes are poorly understood. Here we show that levodopa-induced dyskinesia in hemiparkinsonian rats is strongly associated with pronounced 80 Hz local field potential oscillations in the primary motor cortex following levodopa treatment. When this oscillation is interrupted by application of a dopamine antagonist onto the cortical surface the dyskinetic symptoms disappear. The finding that abnormal cortical oscillations are a key pathophysiological mechanism calls for a revision of the prevailing hypothesis that links levodopa-induced dyskinesia to an altered sensitivity to dopamine only in the striatum. Apart from having important implications for the treatment of Parkinson's disease, the discovered pathophysiological mechanism may also play a role in several other psychiatric and neurological conditions involving cortical dysfunction.
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| 11. |
- Hilbert, Kevin, et al.
(författare)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
-
Ingår i: The American Journal of Psychiatry. - 1535-7228.
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Tidskriftsartikel (refereegranskat)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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| 12. |
- Ivica, Nedjeljka, et al.
(författare)
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Changes in neuronal activity of cortico-basal ganglia-thalamic networks induced by acute dopaminergic manipulations in rats
- 2018
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X. ; 47:3, s. 236-250
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Tidskriftsartikel (refereegranskat)abstract
- The basal ganglia are thought to be particularly sensitive to changes in dopaminergic tone, and the realization that reduced dopaminergic signaling causes pronounced motor dysfunction is the rationale behind dopamine replacement therapy in Parkinson's disease. It has, however, proven difficult to identify which neurophysiological changes that ultimately lead to motor dysfunctions. To clarify this, we have here recorded neuronal activity throughout the cortico-basal ganglia-thalamic circuits in freely behaving rats during periods of immobility following acute dopaminergic manipulations, involving both vesicular dopamine depletion and antagonism of D1 and D2 type dopamine receptors. Synchronized and rhythmic activities were detected in the form of betaband oscillations in local field potentials and as cortical entrainment of action potentials in several basal ganglia structures. Analyses of the temporal development of synchronized oscillations revealed a spread from cortex to gradually also include deeper structures. In addition, firing rate changes involving neurons in all parts of the network were observed. These changes were typically relatively balanced within each structure, resulting in negligible net rate changes. Animals treated with D1 receptor antagonist showed a rapid onset of hypokinesia that preceded most of the neurophysiological changes, with the exception of these balanced rate changes. Parallel rate changes in functionally coupled ensembles of neurons in different structures may therefore be the first step in a cascade of neurophysiological changes underlying motor symptoms in the parkinsonian state. We suggest that balanced rate changes in distributed networks are possible mechanism of disease that should be further investigated in conditions involving dopaminergic dysfunction.
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| 13. |
- Ivica, Nedjeljka, et al.
(författare)
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Design of a high-density multi-channel electrode for multi-structure parallel recordings in rodents
- 2014
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Ingår i: 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). - 1557-170X. ; , s. 393-396
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Konferensbidrag (refereegranskat)abstract
- In neurophysiology, investigating brain connectivity within and between different brain structures is of fundamental importance for understanding nervous system function and its relation to behavior. Yet, parallel recordings in multiple brain structures is highly challenging, especially in rodents, which are most commonly employed in neurophysiological research but rather small in size. In this study, the design and manufacturing of a high-density multi-channel electrode for chronic, multi-structure parallel recordings in rats is presented and exemplified with functional neuronal recordings from 128 recording channels, placed bilaterally in eight different brain structures, in an awake, freely moving animal.
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| 14. |
- Ivica, Nedjeljka, et al.
(författare)
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Differential effects of skilled reaching training on the temporal and spatial organization of somatosensory input to cortical and striatal motor circuits
- 2022
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 127:1, s. 225-238
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Tidskriftsartikel (refereegranskat)abstract
- It has been hypothesized that to perform sensorimotor transformations efficiently, somatosensory information being fed back to a particular motor circuit is organized in accordance with the mechanical loading patterns of the skin that result from the motor activity generated by that circuit. Rearrangements of sensory information to different motor circuits could in this respect constitute a key component of sensorimotor learning. We here explored whether the organization of tactile input from the plantar forepaw of the rat to cortical and striatal circuits is affected by a period of extensive sensorimotor training in a skilled reaching and grasping task. Our data show that the representation of tactile stimuli in terms of both temporal and spatial response patterns changes as a consequence of the training and that spatial changes particularly involve the primary motor cortex. Based on the observed reorganization, we propose that reshaping of the spatiotemporal representation of the tactile afference to motor circuits is an integral component of the learning process that underlies skill acquisition in reaching and grasping.
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| 15. |
- Kursiša, Anta, et al.
(författare)
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Sprachenexpedition rund um die Ostsee : Unterrichtsmaterialien zur Mehrsprachigkeit mit Deutsch
- 2022
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Rapport (populärvet., debatt m.m.)abstract
- Das Material ist im Rahmen des Goethe-Institut-Projektes „Sprachenexpedition rund um die Ostsee“ entstanden und bereits von Lehrkräften in baltischen und nordischen Ländern eingesetzt worden. Die Lernenden beschäftigen sich in sechs Themeneinheiten mit ihrer eigenen inneren und äußeren Mehrsprachigkeit, mit der ihrer Umgebung und ihres Landes, mit Sprachenvergleich und den Grundlagen des Verstehens fremder Sprachen. Dabei laden alle Themen auch zum Vergleich und Austausch ein: Kooperieren Sie mit Lehrkräften in anderen Schulen bzw. Ländern, um die Ergebnisse der Arbeit mit dem Material miteinander auszutauschen – als Grundlage für weiteres Lernen.Das Lehrmaterial stützt sich auf die Prinzipien der Mehrsprachigkeitsdidaktik: Die Lernenden vergleichen, entdecken das Bekannte in neuen Sprachen und denken über Unterschiede und Gemeinsamkeiten zwischen den unterschiedlichen Sprachen nach. Das gesamte Lehrmaterial besteht aus den Arbeitsblättern, die Sie ausdrucken und den Lernenden aushändigen können, und aus den Lehrerhandreichungen zu jedem Arbeitsblatt, in denen Sie mehr über die theoretischen Hintergründe erfahren und Empfehlungen zur Durchführung der Unterrichtseinheit erhalten. In einer siebten Einheit finden Sie Vorschläge für Online-Begegnungen zwischen beteiligten Klassen, damit die Schülerinnen und Schüler ihre Arbeitsergebnisse selber präsentieren und so ins Gespräch miteinander kommen können.
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| 16. |
- Lejaeghere, Kurt, et al.
(författare)
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Reproducibility in density functional theory calculations of solids.
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 351:6280, s. 1415-1422
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Tidskriftsartikel (refereegranskat)abstract
- The widespread popularity of density functional theory has given rise to an extensive range of dedicated codes for predicting molecular and crystalline properties. However, each code implements the formalism in a different way, raising questions about the reproducibility of such predictions. We report the results of a community-wide effort that compared 15 solid-state codes, using 40 different potentials or basis set types, to assess the quality of the Perdew-Burke-Ernzerhof equations of state for 71 elemental crystals. We conclude that predictions from recent codes and pseudopotentials agree very well, with pairwise differences that are comparable to those between different high-precision experiments. Older methods, however, have less precise agreement. Our benchmark provides a framework for users and developers to document the precision of new applications and methodological improvements.
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| 17. |
- Ottová-Jordan, Veronika, et al.
(författare)
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Trends in health complaints from 2002 to 2010 in 34 countries and their association with health behaviours and social context factors at individual and macro-level
- 2015
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Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 25:2, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This article describes trends and stability over time in health complaints in adolescents from 2002 to 2010 and investigates associations between health complaints, behavioural and social contextual factors at individual level and economic factors at macro-level.METHODS: Comprising N = 510 876 11-, 13- and 15-year-old children and adolescents in Europe, North America and Israel, data came from three survey cycles of the international Health Behaviour in School-aged Children (HBSC) study. Age- and gender-adjusted trends in health complaints were examined in each country by means of linear regression. By using the country as the random effects variable, we tested to what extent individual and contextual variables were associated with health complaints.RESULTS: Significant associations are stronger for individual level determinants (e.g. being bullied, smoking) than for determinants at macro-level (e.g. GDP, Gini), as can be seen by the small effect sizes (less than 5% for different trends). Health complaints are fairly stable over time in most countries, and no clear international trend in health complaints can be observed between 2002 and 2010. The most prominent stable determinants were being female, being bullied, school pressure and smoking.CONCLUSION: Factors associated with health complaints are more related to the proximal environment than to distal macro-level factors. This points towards intensifying targeted interventions, (e.g. for bullying) and also targeting specific risk groups. The comparably small effect size at country-level indicates that country-level factors have an impact on health and should not be ignored.
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| 18. |
- Ottová-Jordan, Veronika, et al.
(författare)
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Trends in health complaints from 2002 to 2010 in 34 countries and their association with health behaviours and social context factors at individual and macro-level
- 2015
-
Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 25:Suppl 2, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This article describes trends and stability over time in health complaints in adolescents from 2002 to 2010 and investigates associations between health complaints, behavioural and social contextual factors at individual level and economic factors at macro-level.METHODS: Comprising N = 510 876 11-, 13- and 15-year-old children and adolescents in Europe, North America and Israel, data came from three survey cycles of the international Health Behaviour in School-aged Children (HBSC) study. Age- and gender-adjusted trends in health complaints were examined in each country by means of linear regression. By using the country as the random effects variable, we tested to what extent individual and contextual variables were associated with health complaints.RESULTS: Significant associations are stronger for individual level determinants (e.g. being bullied, smoking) than for determinants at macro-level (e.g. GDP, Gini), as can be seen by the small effect sizes (less than 5% for different trends). Health complaints are fairly stable over time in most countries, and no clear international trend in health complaints can be observed between 2002 and 2010. The most prominent stable determinants were being female, being bullied, school pressure and smoking.CONCLUSION: Factors associated with health complaints are more related to the proximal environment than to distal macro-level factors. This points towards intensifying targeted interventions, (e.g. for bullying) and also targeting specific risk groups. The comparably small effect size at country-level indicates that country-level factors have an impact on health and should not be ignored.
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| 19. |
- Pichora-Fuller, Kathleen M., et al.
(författare)
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Hearing Impairment and Cognitive Energy: The Framework for Understanding Effortful Listening (FUEL)
- 2016
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Ingår i: Ear and Hearing. - : LIPPINCOTT WILLIAMS & WILKINS. - 0196-0202 .- 1538-4667. ; 37, s. 5S-27S
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Tidskriftsartikel (refereegranskat)abstract
- The Fifth Eriksholm Workshop on "Hearing Impairment and Cognitive Energy" was convened to develop a consensus among interdisciplinary experts about what is known on the topic, gaps in knowledge, the use of terminology, priorities for future research, and implications for practice. The general term cognitive energy was chosen to facilitate the broadest possible discussion of the topic. It goes back to Titchener (1908) who described the effects of attention on perception; he used the term psychic energy for the notion that limited mental resources can be flexibly allocated among perceptual and mental activities. The workshop focused on three main areas: (1) theories, models, concepts, definitions, and frameworks; (2) methods and measures; and (3) knowledge translation. We defined effort as the deliberate allocation of mental resources to overcome obstacles in goal pursuit when carrying out a task, with listening effort applying more specifically when tasks involve listening. We adapted Kahnemans seminal (1973) Capacity Model of Attention to listening and proposed a heuristically useful Framework for Understanding Effortful Listening (FUEL). Our FUEL incorporates the well-known relationship between cognitive demand and the supply of cognitive capacity that is the foundation of cognitive theories of attention. Our FUEL also incorporates a motivation dimension based on complementary theories of motivational intensity, adaptive gain control, and optimal performance, fatigue, and pleasure. Using a three-dimensional illustration, we highlight how listening effort depends not only on hearing difficulties and task demands but also on the listeners motivation to expend mental effort in the challenging situations of everyday life.
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| 20. |
- Poli, Sven, et al.
(författare)
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Penumbral Rescue by normobaric O?=?O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial
- 2024
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Ingår i: INTERNATIONAL JOURNAL OF STROKE. - 1747-4930 .- 1747-4949. ; 19:1, s. 120-126
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs.Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.Methods and design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.Study outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted.Sample size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation.Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia.
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| 21. |
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| 22. |
- Richter, Ulrike, et al.
(författare)
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A novel approach to propagation pattern analysis in intracardiac atrial fibrillation signals
- 2011
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Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 1573-9686 .- 0090-6964. ; 39, s. 310-323
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to investigate propagation patterns in intracardiac signals recorded during atrial fibrillation (AF) using an approach based on partial directed coherence (PDC), which evaluates directional coupling between multiple signals in the frequency domain. The PDC is evaluated at the dominant frequency of AF signals and tested for significance using a surrogate data procedure specifically designed to assess causality. For significantly coupled sites, the approach allows also to estimate the delay in propagation. The methods potential is illustrated with two simulation scenarios based on a detailed ionic model of the human atrial myocyte as well as with real data recordings, selected to present typical propagation mechanisms and recording situations in atrial tachyarrhythmias. In both simulation scenarios the significant PDCs correctly reflect the direction of coupling and thus the propagation between all recording sites. In the real data recordings, clear propagation patterns are identified which agree with previous clinical observations. Thus, the results illustrate the ability of the novel approach to identify propagation patterns from intracardiac signals during AF, which can provide important information about the underlying AF mechanisms, potentially improving the planning and outcome of arrhythmia ablation.
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| 23. |
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| 24. |
- Richter, Ulrike, et al.
(författare)
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Mechanisms underlying cortical resonant states: implications for levodopa-induced dyskinesia
- 2013
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Ingår i: Reviews in the Neurosciences. - : Walter de Gruyter GmbH. - 0334-1763 .- 2191-0200. ; 24:4, s. 415-429
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Tidskriftsartikel (refereegranskat)abstract
- A common observation in recordings of neuronal activity from the cerebral cortex is that populations of neurons show patterns of synchronized oscillatory activity. However, it has been suggested that neuronal synchronization can, in certain pathological conditions, become excessive and possibly have a pathogenic role. In particular, aberrant oscillatory activation patterns have been implicated in conditions involving cortical dysfunction. We here review the mechanisms thought to be involved in the generation of cortical oscillations and discuss their relevance in relation to a recent finding indicating that high-frequency oscillations in the cerebral cortex have an important role in the generation of levodopa-induced dyskinesia. On the basis of these insights, it is suggested that the identification of physiological changes associated with symptoms of disease is a particularly important first step toward a more rapid development of novel treatment strategies.
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| 25. |
- Richter, Ulrike, et al.
(författare)
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Propagation pattern analysis during atrial fibrillation based on sparse modeling
- 2012
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Ingår i: IEEE Transactions on Biomedical Engineering. - 1558-2531. ; 59:5, s. 1319-1328
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedIn this study, sparse modeling is introduced for the estimation of propagation patterns in intracardiac atrial fibrillation (AF) signals. The estimation is based on the partial directed coherence function, derived from fitting a multivariate autoregressive model to the observed signal using least-squares (LS) estimation. The propagation pattern analysis incorporates prior information on sparse coupling as well as the distance between the recording sites. Two optimization methods are employed for estimation of the model parameters, namely, the adaptive group least absolute selection and shrinkage operator (aLASSO), and a novel method named the distance-adaptive group LASSO (dLASSO). Using simulated data, both optimization methods were superior to LS estimation with respect to detection and estimation performance. The normalized error between the true and estimated model parameters dropped from 0.20 +/- 0.04 for LS estimation to 0.03 +/- 0.01 for both aLASSO and dLASSO when the number of available data samples exceeded the number of model parameters by a factor of 5. For shorter data segments, the error reduction was more pronounced and information on the distance gained in importance. Propagation pattern analysis was also studied on intracardiac AF data, the results showing that the identification of propagation patterns is substantially simplified by the sparsity assumption.
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| 26. |
- Richter, Ulrike, et al.
(författare)
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Propagation pattern analysis during atrial fibrillation based on the adaptive group LASSO
- 2011
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Ingår i: Engineering in Medicine and Biology Society, EMBC, 2011 Annual International Conference of the IEEE. - 1557-170X. - 9781424441211 ; 3, s. 5535-5538
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Konferensbidrag (refereegranskat)abstract
- The present study introduces sparse modeling for the estimation of propagation patterns in intracardiac atrial fibrillation (AF) signals. The estimation is based on the partial directed coherence (PDC) function, derived from fitting a multivariate autoregressive model to the observed signals. A sparse optimization method is proposed for estimation of the model parameters, namely, the adaptive group least absolute selection and shrinkage operator (aLASSO). In simulations aLASSO was found superior to the commonly used least-squares (LS) estimation with respect to estimation performance. The normalized error between the true and estimated model parameters dropped from 0.20±0.04 for LS estimation to 0.03±0.01 for aLASSO when the number of available data samples exceeded the number of model parameters by a factor of 5. The error reduction was more pronounced for short data segments. Propagation patterns were also studied on intrac-ardiac AF data, the results showing that the identification of propagation patterns is substantially simplified by the sparsity assumption.
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| 27. |
- Richter, Ulrike, et al.
(författare)
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Right atrial organization and wavefront analysis in atrial fibrillation.
- 2009
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Ingår i: Medical & Biological Engineering & Computing. - : Springer Science and Business Media LLC. - 0140-0118 .- 1741-0444. ; 47, s. 1237-1246, s. 271-278
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to develop techniques to quantify the propagation pattern of the electrical activation during atrial fibrillation (AF) along a one-dimensional catheter. Taking intra-atrial signal organization aspects into account, the atrial activations are detected and combined into wavefronts. Parameters describing wavefront consistency and activation order along the catheter are defined, and the relationship of wavefront consistency to body surface parameters, namely AF frequency and exponential decay, is investigated. The database consisted of 26 10-s recordings from patients during drug-refractory AF, in which five adjacent bipolar electrograms from a catheter in the right atrium were recorded. The 12-lead ECG was recorded simultaneously. The degree of wavefront consistency provided insights into the temporal variability of the activation order, an aspect which was not reflected by the body surface parameters. However, AF frequency was able to distinguish between recordings with different degrees of intra-atrial signal organization (p = 0.008).
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| 28. |
- Richter, Ulrike, et al.
(författare)
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Spatial characteristics of atrial fibrillation electrocardiograms
- 2008
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 41:2, s. 165-172
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The present study investigates spatial properties of atrial fibrillation (AF) by analyzing vectorcardiogram loops synthesized from 12-lead electrocardiograms (ECGs). METHODS: After atrial signal extraction, spatial properties are characterized through analysis of successive, fixed-length signal segments and expressed in loop orientation, that is, azimuth and elevation, as well as in loop morphology, that is, planarity and planar geometry. It is hypothesized that more organized AF, expressed by a lower AF frequency, is associated with decreased variability in loop morphology. Atrial fibrillation frequency is determined using spectral analysis. RESULTS: Twenty-six patients with chronic AF were analyzed using 60-second ECG recordings. Loop orientation was similar when determined from either entire 60- or 1-second segments. For 1-second segments, the correlation between AF frequency and the parameters planarity and planar geometry were 0.608 (P < .001) and 0.543 (P < .005), respectively. CONCLUSIONS: Quantification of AF organization based on AF frequency and spatial characteristics from the ECG is possible. The results suggested a relatively weak coupling between loop morphology and AF frequency when determined from the surface ECG.
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| 29. |
- Richter, Ulrike
(författare)
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Spatial characteristics of atrial fibrillation using body surface and intra-atrial signals
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This licentiate thesis is in the field of biomedical signal processing with main focus on processing of cardiac signals measured on the body surface or invasively from patients with atrial fibrillation (AF). The first part addresses spatial analysis of AF using VCG data synthesized from the 12-lead ECG. Two parameters each are extracted to characterize the spatial orientation as well as the spatial extent of the VCG data during AF. In addition, the relation of the parameters to AF organization, which is expressed in AF frequency, is evaluated. It is concluded that the quantification of AF organization based on AF frequency and spatial characteristics from the surface ECG is possible. The results suggest a relatively weak coupling between loop morphology and AF frequency when determined from the surface ECG. In the second part, a novel technique to quantify the propagation pattern of the electrical activation during AF along a one-dimensional catheter in the right atrium is presented. Taking intra-atrial signal organization aspects into account, the atrial activations are detected from the electrograms and combined into wavefronts. Parameters related to the consistency of the detected wavefronts over time and the activation order along the catheter are developed and their relationship to body surface measures such as AF frequency is investigated. While the degree of wavefront consistency is not reflected by the body surface measures, AF frequency is able to distinguish between recordings with different degrees of intra-atrial signal organization, supporting the role of AF frequency as an organization measure of AF.
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| 30. |
- Richter, Ulrike, et al.
(författare)
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Spatial characteristics of atrial fibrillation using the surface ECG
- 2007
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Ingår i: Computers in Cardiology. - 0276-6574. - 9781424425334 ; 34, s. 273-276
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Konferensbidrag (refereegranskat)abstract
- The present study investigates spatial properties of atrial fibrillation (AF) by analyzing VCG loops synthesized from 12-lead ECGs. During intervals with ventricular activity, the atrial signal is extracted using spatiotemporal QRST cancellation, thus making continuous f-wave analysis possible. Spatial properties are characterized through joint analysis of successive fixed-length signal segments, either of 1-s length or related to the typical length of an f-wave. The spatial properties are expressed in terms of loop orientation, i.e., angles of azimuth and elevation, as well as in morphologic terms such as planarity and planar geometry of the loops and related temporal variability. Several parameters have been suggested to characterize the degree of AF organization from electrogram analysis, but only a few parameters for noninvasive, ECG-based characterization of which AF frequency is the most studied. This parameter is related to atrial refractoriness and reflects AF organization. In the present study, the significance of spatial (loop morphology) parameters is studied in relation to AF frequency, hypothesizing that more organized AF, being expressed by a lower frequency, is associated with decreased variability in loop morphology. A total of 26 patients with chronic AF were analyzed with respect to spatial properties, using 60-s ECG recordings. For the database AF frequency ranged from 3.9 to 7.7 Hz, with a mean of 6.4±1.0 Hz (mean±std). The results showed that loop orientation can be determined from global analysis (i.e., the entire 60-s segment was used for determining the two angles) or the mean of segment-based analysis, both types of analysis leading to similar results. The hypothesis that more organized AF is associated with decreased variability in loop morphology was to some extent confirmed for the parameters planarity and planar geometry; for 1-s segments, the correlation to AF frequency was 0.608 (p<0.001) and 0.543 (p<0.005). This finding also applied to segment lengths related to f-wave duration. In conclusion, the simpler analysis based on 1-s segments may be preferred since it does not require f-wave delineation. Global analysis and the mean of segment-based analysis (1-s segments) showed increased planarity and decreased planar geometry for lower AF frequencies, possibly related to higher similarity of successive loops in more organized AF.
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| 31. |
- Richter, Ulrike
(författare)
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Spatial Characterization and Estimation of Intracardiac Propagation Patterns During Atrial Fibrillation
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This doctoral thesis is in the field of biomedical signal processing with focus on methods for the analysis of atrial fibrillation (AF). Paper I of the present thesis addresses the challenge of extracting spatial properties of AF from body surface signals. Different parameters are extracted to estimate the preferred direction of atrial activation and the complexity of the atrial activation pattern. In addition, the relation of the spatial properties to AF organization, which is quantified by AF frequency, is evaluated. While no significant correlation between the preferred direction of atrial activation and AF frequency could be observed, the complexity of the atrial activation pattern was found to increase with AF frequency. The remaining three papers deal with the analysis of the propagation of the electrical activity in the atria during AF based on intracardiac signals. In Paper II, a time-domain method to quantify propagation patterns along a linear catheter based on the detected atrial activation times is developed. Taking aspects on intra-atrial signal organization into account, the detected activation times are combined into wavefronts, and parameters related to the consistency of the wavefronts over time and the activation order along the catheter are extracted. Furthermore, the potential relationship of the extracted parameters to established measures from body surface signals is investigated. While the degree of wavefront consistency was not reflected by the applied body surface measures, AF frequency could distinguish between recordings with different degrees of intra-atrial signal organization. This supports the role of AF frequency as an organization measure of AF. In Paper III, a novel method to analyze intracardiac propagation patterns based on causality analysis in the frequency domain is introduced. In particular, the approach is based on the partial directed coherence (PDC), which evaluates directional coupling between multiple signals in the frequency domain. The potential of the method is illustrated with simulation scenarios based on a detailed ionic model of the human atrial cell as well as with real data recordings, selected to present typical propagation mechanisms and recording situations in atrial tachyarrhythmias. For simulated data, the PDC is correctly reflecting the direction of coupling and thus the propagation between all recording sites. For real data, clear propagation patterns are identified which agree with previous clinical observations. Thus, the results illustrate the ability of the novel approach to identify propagation patterns from intracardiac signals during AF which can provide important information about the underlying AF mechanisms, potentially improving the planning and outcome of ablation. However, spurious couplings over long distances can be observed when analyzing real data comprised by a large number of simultaneously recorded signals, which gives room for further improvement of the method. The derivation of the PDC is entirely based on the fit of a multivariate autoregressive (MVAR) model, commonly estimated by the least-squares (LS) method. In Paper IV, the adaptive group least absolute selection and shrinkage operator (LASSO) is introduced in order to avoid overfitting of the MVAR model and to incorporate prior information such as sparsity of the solution. The sparsity can be motivated by the observation that direct couplings over longer distances are likely to be zero during AF; an information which has been further incorporated by proposing distance-adaptive group LASSO. In simulations, adaptive and distance-adaptive group LASSO are found to be superior to LS estimation in terms of both detection and estimation accuracy. In addition, the results of both simulations and real data analysis indicate that further improvements can be achieved when the distance between the recording sites is known or can be estimated. This further promotes the PDC as a method for analysis of AF propagation patterns, which may contribute to a better understanding of AF mechanisms as well as improved AF treatment.
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| 32. |
- Richter, Ulrike, et al.
(författare)
-
Wavefront detection from intra-atrial recordings
- 2007
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Ingår i: Computers in Cardiology. - 0276-6574. - 9781424425334 ; 34, s. 97-100
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Konferensbidrag (refereegranskat)abstract
- The present study deals with detection of intra-atrial wavefronts from atrial activation times in adjacent bipolar electrograms. A statistic of the delays within each wave-front was calculated and served as a basis for quantifying the wavefront consistency as well as the propagation of the electrical activity along the catheter. The database consisted of 19 patients for which five electrograms were recorded simultaneously during 10 s. The analysis resulted in 38plusmn2 complete wavefronts per patient, i.e., wavefronts consisting of one activation from each recording site. Two parameters were evaluated for quantifying wavefront consistency, which together with the propagation profile well reflect the overall wavefront timing. In most cases, electrical activity was observed first in the high septal right atrium, and then spread along the catheter.
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| 33. |
- Santana, Maxwell B, et al.
(författare)
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Spinal cord stimulation alleviates motor deficits in a primate model of Parkinson disease.
- 2014
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273. ; 84:4, s. 716-722
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Tidskriftsartikel (refereegranskat)abstract
- Although deep brain electrical stimulation can alleviate the motor symptoms of Parkinson disease (PD), just a small fraction of patients with PD can take advantage of this procedure due to its invasive nature. A significantly less invasive method-epidural spinal cord stimulation (SCS)-has been suggested as an alternative approach for symptomatic treatment of PD. However, the mechanisms underlying motor improvements through SCS are unknown. Here, we show that SCS reproducibly alleviates motor deficits in a primate model of PD. Simultaneous neuronal recordings from multiple structures of the cortico-basal ganglia-thalamic loop in parkinsonian monkeys revealed abnormal highly synchronized neuronal activity within each of these structures and excessive functional coupling among them. SCS disrupted this pathological circuit behavior in a manner that mimics the effects caused by pharmacological dopamine replacement therapy or deep brain stimulation. These results suggest that SCS should be considered as an additional treatment option for patients with PD.
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| 34. |
- Schiele, Miriam A., et al.
(författare)
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Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders : A meta-analysis
- 2021
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 44, s. 105-120
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Tidskriftsartikel (refereegranskat)abstract
- There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.
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| 35. |
- Tamté, Martin, et al.
(författare)
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Systems level neurophysiological state characteristics for drug evaluation in an animal model of levodopa-induced dyskinesia.
- 2016
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 115:3, s. 1713-1729
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Tidskriftsartikel (refereegranskat)abstract
- Disorders affecting the central nervous system have proven particularly hard to treat and disappointingly few of novel therapies have reached the clinics in the last decades. A better understanding of the physiological processes in the brain underlying various symptoms could therefore greatly improve the rate of progress in this field. We here show how systems level descriptions of different brain states reliably can be obtained through a newly developed method based on large-scale recordings in distributed neural networks encompassing several different brain structures. Using this technology we characterize the neurophysiological states associated with parkinsonism and levodopa-induced dyskinesia in a rodent model of Parkinson's disease together with pharmacological interventions aimed at reducing dyskinetic symptoms. Our results show that the obtained electrophysiological data add significant information to conventional behavioral evaluations and hereby elucidates the underlying effects of treatments in greater detail. Taken together, these results potentially open up for studies of neurophysiological mechanisms underlying symptoms in a wide range of neurologic and psychiatric conditions that until now have been very hard to investigate in animal models of disease.
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| 36. |
- Trost, Fabian, et al.
(författare)
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Imaging via Correlation of X-Ray Fluorescence Photons
- 2023
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 130:17
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that x-ray fluorescence emission, which cannot maintain a stationary interference pattern, can be used to obtain images of structures by recording photon-photon correlations in the manner of the stellar intensity interferometry of Hanbury Brown and Twiss. This is achieved utilizing femtosecondduration pulses of a hard x-ray free-electron laser to generate the emission in exposures comparable to the coherence time of the fluorescence. Iterative phasing of the photon correlation map generated a model-free real-space image of the structure of the emitters. Since fluorescence can dominate coherent scattering, this may enable imaging uncrystallised macromolecules.
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| 37. |
- Vedde, Jan, et al.
(författare)
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Technical Parameters Used in PV Financial Models: Review and Analysis
- 2016
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Ingår i: 32nd European Photovoltaic Solar Energy Conference and Exhibition. - 3936338418 ; , s. 2897-2902
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Konferensbidrag (refereegranskat)abstract
- When photovoltaic (PV) projects are developed and constructed for investment purposes, financing from professional investors and banks are required, and financial models are developed that describe the expected cash-flow generated by the PV plant over the economic lifetime of the project. The calculation is based on models that require both technical and financial inputs. In this paper we will review and analyse the technical assumptions in these models and discuss how the technical assumptions are typically used and to what extent the uncertainty related to the input parameters are appropriately addressed. Finally, a calculation and visualisation method is presented that highlights the nature and effect of this uncertainty.
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| 38. |
- Waldkirch, Eginhard S., et al.
(författare)
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Expression of cyclic AMP-dependent protein kinase isoforms in human cavernous arteries : functional significance and relation to phosphodiesterase type 4
- 2010
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Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6095 .- 1743-6109. ; 7:6, s. 2104-2111
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The cyclic adenosine monophosphate-dependent protein kinase (cAK) is considered a key protein in the control of smooth muscle tone in the cardiovascular system. There is evidence that erectile dysfunction might be linked to systemic vascular disorders and arterial insufficiency, subsequently resulting in structural changes in the penile tissue. The expression and significance of cAK in human cavernous arteries (HCA) have not been evaluated.AIMS: To evaluate the expression of cAK isoforms in HCA and examine the role of cAK in the cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-mediated control of penile vascular smooth muscle.METHODS: The expression and distribution of phosphodiesterase type 4 (PDE4) and cAK isoforms in sections of HCA were investigated by means of immunohistochemistry and Western blot analysis. The effects of the cAK inhibitor Rp-8-CPT-cAMPS on the relaxation of isolated preparations of HCA (diameter > 100 µm) induced by rolipram, sildenafil, tadalafil, and vardenafil were studied using the organ bath technique.MAIN OUTCOME MEASURES: Investigate the expression of cAK in relation to α-actin and PDE4 in HCA and evaluate the effects of an inhibition of cAK on the relaxation induced by inhibitors of PDE4 and PDE5 of isolated penile arteries.RESULTS: Immunosignals specific for cAKIα, IIα, and IIβ were observed within the wall of HCA. Double stainings revealed colocalization of cAK with α-actin and PDE4. The expression of cAK isoforms was confirmed by Western blot analysis. The reversion of tension induced by inhibitors of PDE4 and PDE5 of isolated penile vascular tissue were attenuated significantly by Rp-8-CPT-cAMPS.CONCLUSIONS: Our results demonstrate the expression of cAK isoforms in the smooth musculature of HCA and its colocalization with PDE4. A significant role for cAK in the regulation mediated by cAMP and cGMP of vascular smooth muscle tone in HCA can also be assumed.
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