Neuronale Synchronisation während perzeptueller Organisation in Schizophrenie-Patienten

Current theories of schizophrenia suggest that the pathophysiology of the disorder may be the result of a deficit in the coordination of neural activity within and between areas of the brain, which may lead to impairments in basic cognitive functions such as contextual disambiguation and dynamic grouping (Phillips and Silverstein, 2003). This notion has been supported by recent studies showing that patients with schizophrenia are characterized by reduced synchronous, oscillatory activity in the gamma-frequency band during sensory processing (Spencer et al. 2003, Green et al. 2003, Wynn et al. 2005). However, it is currently unclear to what extent high-frequency gamma-band oscillations (> 60 Hz) contribute to impaired neural synchronization as research has so far focussed on gamma-band oscillations between 30 and 60 Hz. In addition, it is not known whether deficits in high-frequency oscillations are already present at the onset of the disorder and to what extent reductions may be related to the confounding influence of antipsychotic medication. Finally, the neural generators underlying impairments in synchronous oscillatory activity in schizophrenia have not been investigated yet. To address these questions, we recorded MEG activity during a visual closure task (Mooney faces task) in medicated chronic schizophrenia patients, drug-naive first-episode schizophrenia patients and healthy controls. MEG data were analysed for spectral power between 25 and 150 Hz, and beamforming techniques were used to localize the sources of oscillatory gamma-band activity. In healthy controls, we observed that the processing of Mooney faces was associated with sustained high-frequency gamma-band activity (> 60 Hz). A time-resolved analysis of the neural generators underlying perceptual closure revealed a network of distributed sources in occipito-temporal, parietal and frontal regions, which were differentially activated during specific time intervals. In chronic schizophrenia patients, we found a pronounced reduction of high-frequency gamma-band oscillatory activity that was accompanied by an impairment in perceptual organization and involved reduced source power in various brain regions associated with perceptual closure. First-episode patients were also characterized by a deficit in high-frequency gamma-band activity and reductions of source power in multiple areas; these impairments, however, were less pronounced than in chronic patients. Regarding behavioral performance, first-episode patients were not impaired in their ability to detect Mooney faces, but exhibited a loss in specificity of face detection. In conclusion, our results suggest that schizophrenia is associated with a widespread reduction in high-frequency oscillations that indicate local network abnormalities. These dysfunctions are independent of medication status and already present at illness onset, suggesting a possible progressive deficit during the course of the disorder.Aktuelle Theorien gehen davon aus, dass die Pathophysiologie der Schizophrenie auf eine Störung in der Koordination neuronaler Prozesse zurückzuführen ist, welche zu einer Beeinträchtigung in der Integration von Informationen führt und sich in Defiziten bei frühen Wahrnehmungsprozessen und höheren kognitiven Funktionen widerspiegelt. Diese Hypothese wird durch eine Reihe von Studien gestützt, die eine Reduktion oszillatorischer Aktivität im Beta- und Gamma-Frequenzband im Elektroenzephalogramm während visueller Wahrnehmungsprozesse bei Patienten mit Schizophrenie nachweisen konnten. Die Bedeutung von hochfrequenten Gamma-Band Oszillationen (> 60 Hz) für das Verständnis von perzeptuellen Dysfunktionen bei Patienten mit Schizophrenie ist jedoch bislang wenig erforscht. Zudem ist unklar, ob und in welchem Umfang eine Veränderung oszillatorischer Aktivität bereits zu Beginn der Erkrankung und ohne den Einfluss von antipsychotischen Medikamenten vorhanden ist. Des Weiteren gibt es bislang keine Befunde zu den neuronalen Quellen, die den Defiziten oszillatorischer Aktivität bei Schizophrenie-Patienten zugrunde liegen. Um diese Fragen zu untersuchen, wurden im Rahmen der vorliegenden Dissertation drei Studien durchgeführt, in denen die Hirnaktivität während einer visuellen Gestaltaufgabe (Mooney faces-Aufgabe) bei chronischen medizierten Schizophrenie-Patienten, ersterkrankten nicht-medizierten Schizophrenie-Patienten sowie bei gesunden Kontrollprobanden mittels Magnetoenzephalographie (MEG) gemessen wurde. Die Auswertung der MEG-Daten beinhaltete auf der Sensoren-Ebene eine Auswertung der spektralen Power zwischen 25 und 150 Hz und auf der Quellen-Ebene eine Rekonstruktion der Generatoren oszillatorischer Aktivität mit Hilfe von Beamforming-Techniken. Die Hauptbefunde lassen sich wie folgt zusammenfassen: Das neuronale Netzwerk perzeptueller Organisation bei Mooney faces zeigte eine ausgeprägte oszillatorische Aktivität im hochfrequenten Gamma-Band (> 60 Hz) in gesunden Kontrollprobanden und umfasste okzipito-temporale, parietale und frontale Areale, die zu verschiedenen Zeitpunkten der Informationsverarbeitung aktiviert wurden. Unsere Ergebnisse lassen vermuten, dass perzeptuelle Organisationsprozesse bei Mooney faces auf einer frühen Interaktion zwischen Arealen beruhen, die mit der Verarbeitung von Schattierungsreizen zusammenhängen, gesichtsspezifischen Arealen, und Arealen, die mit dem Abruf von Informationen aus dem Langzeitgedächtnis in Verbindung stehen. Im Vergleich zu den Kontrollprobanden zeigten chronische Schizophrenie-Patienten ein deutliches Defizit in der hochfrequenten (60 – 120 Hz) Gamma-Band Power, welches mit reduzierten Detektionsraten bei der Mooney faces-Aufgabe und mit verringerten Aktivierungen in den für perzeptuelle Organisationsprozesse relevanten Arealen einherging. Ersterkrankte nicht-medizierte Schizophrenie-Patienten zeigten ebenfalls eine Reduktion hochfrequenter Gamma-Band Power in verschiedenen Hirnarealen. Dieses Defizit war jedoch weniger stark ausgeprägt als in den chronischen Schizophrenie-Patienten. Im Gegensatz zu den chronischen Patienten zeigten die ersterkrankten Patienten keine Beeinträchtigung bei der Detektion von Gesichtern in aufrecht präsentierten Mooney face Stimuli; jedoch wiesen sie ein Defizit in der Diskrimination zwischen Gesichtern und Nicht-Gesichtern auf. Unsere Befunde deuten darauf hin, dass bei Patienten mit Schizophrenie ausgeprägte Defizite in lokalen Synchronisationsprozessen vorliegen, welche mit perzeptuellen Dysfunktionen einhergehen. Die beeinträchtigte Koordination neuronaler Aktivität könnte auf Veränderungen in GABAergen und glutamatergen Neurotransmittersystemen bei Schizophrenie-Patienten zurückzuführen sein. Unsere Ergebnisse zeigen weiterhin, dass Beeinträchtigungen neuronaler Synchronisation bereits zu Beginn der Erkrankung und ohne den Einfluss von antipsychotischer Medikation vorhanden sind. Die stärkere Beeinträchtigung in den chronischen im Vergleich zu den ersterkrankten Patienten deutet auf einen progressiven Verlauf der Beeinträchtigung oszillatorischer Aktivität bei Schizophrenie-Patienten hin

One year after mild COVID-19: the majority of patients maintain specific immunity, but one in four still suffer from long-term symptoms

After COVID-19, some patients develop long-term symptoms. Whether such symptoms correlate with immune responses, and how long immunity persists, is not yet clear. This study focused on mild COVID-19 and investigated correlations of immunity with persistent symptoms and immune longevity. Persistent complications, including headache, concentration difficulties and loss of smell/taste, were reported by 51 of 83 (61%) participants and decreased over time to 28% one year after COVID-19. Specific IgA and IgG antibodies were detectable in 78% and 66% of participants, respectively, at a 12-month follow-up. Median antibody levels decreased by approximately 50% within the first 6 months but remained stable up to 12 months. Neutralizing antibodies could be found in 50% of participants; specific INFgamma-producing T-cells were present in two thirds one year after COVID-19. Activation-induced marker assays identified specific T-helper cells and central memory T-cells in 80% of participants at a 12-month follow-up. In correlative analyses, older age and a longer duration of the acute phase of COVID-19 were associated with higher humoral and T-cell responses. A weak correlation between long-term loss of taste/smell and low IgA levels was found at early time points. These data indicate a long-lasting immunological memory against SARS-CoV-2 after mild COVID-19

Performance Assessment of Emergency Teams and Communication in Trauma Care (PERFECT checklist)-Explorative analysis, development and validation of the PERFECT checklist: Part of the prospective longitudinal mixed-methods EPPTC trial

BACKGROUND:Trainings in emergency medicine are well structured, but examinations are rarely validated. We are evaluating the impact of pre-hospital emergency trainings on participants and patient care and developed and validated a checklist to assess emergency trainings. METHODS:We used videos recorded at the time points directly before (t0), directly after (t1), and one year after (t2) training to develop the PERFECT checklist (Performance Assessment of Emergency Teams and Communication in Trauma Care). The videos were assessed using semi-qualitative/linguistic analysis as well as expert panel appraisal and recommendations using the Delphi method. The checklist was tested for validity and reliability. RESULTS:The inter-rater reliability (ICC = 0.99) and internal consistency (α = 0.99) were high. Concurrent validity was moderate to high (r = 0.65 -r = 0.93 (p<0.001)). We included scales for procedures, non-technical skills, technical skills and global performance. The procedures were done faster in the mean over the timeline (t0: 2:29, 95%CI 1:54-3:03 min., t1: 1:11, 95%C 0:53-1:30 min, t2: 1:14, 95%CI 0:56-1:31 min.). All experts rated the recorded scenarios at t0 with the lowest sum score (mean 31±8), with a significantly better performance of the teams at t1 (mean 69±7). The performance at t2 (mean 66 ± 13) was slightly lower than at t1, but still better than at t0. At t1 and t2, linguistic analysis showed a change in the team leaders communication behaviour, which can be interpreted as a surrogate parameter for reduced stress. CONCLUSION:The PERFECT checklist has a good validity and high reliability for assessing trauma procedures and teamwork

Deficits in high- (&gt;60Hz) gamma-band oscillations during visual processing in schizophrenia. Front

Current theories of the pathophysiology of schizophrenia have focused on abnormal temporal coordination of neural activity. Oscillations in the gamma-band range (&gt;25 Hz) are of particular interest as they establish synchronization with great precision in local cortical networks. However, the contribution of high gamma (&gt;60 Hz) oscillations toward the pathophysiology is less established. To address this issue, we recorded magnetoencephalographic (MEG) data from 16 medicated patients with chronic schizophrenia and 16 controls during the perception of Mooney faces. MEG data were analysed in the 25-150 Hz frequency range. Patients showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces while responses to inverted stimuli were intact. Impaired processing of Mooney faces in schizophrenia patients was accompanied by a pronounced reduction in spectral power between 60-120 Hz (effect size: d = 1.26) which was correlated with disorganized symptoms (r = −0.72). Our findings demonstrate that deficits in high gamma-band oscillations as measured by MEG are a sensitive marker for aberrant cortical functioning in schizophrenia, suggesting an important aspect of the pathophysiology of the disorder