Multisensorische Integration natürlicher Objekte mit dem Schwerpunkt audio-haptischer und audio-visuo-haptischer Integration - eine fMRT-Studie

Die Wahrnehmung unserer Umwelt erfolgt über verschiedene Sinnesmodalitäten, deren Informationen bevorzugt in bestimmten Hirnarealen verarbeitet werden und sich schließlich zu einem kohärenten Bild ergänzen. Wie diese Prozesse ablaufen und durch welche Vorgänge die Wahrnehmungen einen einheitlichen Sinneseindruck formen, sind fundamentale Fragen der kognitiven Neurowissenschaft. Ziel der vorliegenden Studie war es, diese sensorischen Verarbeitungsprozesse genauer zu untersuchen und bisherige Ergebnisse zu bestätigen sowie neue Erkenntnisse bezüglich audio-haptischer und audio-visuo-haptischer Integration zu gewinnen. Weiterhin sollten angemessene Kriterien für die Auswertung der Daten untersucht werden mit dem Schwerpunkt sinnvoller Kontrollbedingungen. Sechzehn Probanden wurden hierzu mittels fMRT während uni-, bi- und trimodaler Stimulation untersucht. Die Stimulation bestand aus der Darbietung von schwarz-weißen Tierbildern, Tierstimmen und Tierfiguren, die einzeln oder in unterschiedlichen Kombinationen präsentiert wurden. Weiterhin gab es eine motorische Kontrollbedingung ohne sensorische Stimulation. Die unisensorischen Ergebnisse fanden sich in den modalitätsspezifischen Kortexarealen und bestätigten zum großen Teil bisherige Erkenntnisse und die Existenz der Was- und Wo-Pfade. Bimodale audio-visuelle Stimulation führte zu Aktivierungen im Temporallappen um den STS/STG, welcher bei audio-visueller Integration von großer Bedeutung ist. Aktivierungen im Gyrus cinguli, Gyrus fusiformis und Precuneus spielen anscheinend eine Rolle bei der Präsentation von familiären Stimuli und kongruenten Darbietungskombinationen. Auf Ebene früher visueller und auditorischer Leitungsbahnen zeigte sich ebenfalls audio-visuelle Interaktion. Visuo-haptische Integration scheint sich nach den vorliegenden Daten im LOtv, IPS und ventralen Zerebellum abzuspielen. LOtv und IPS sind vermutlich insbesondere für die Verarbeitung von geometrischen Formen von Bedeutung. Im ventralen Zerebellum kommt es durch kortiko-zerebelläre Verschaltungen zur Beteiligung bei visuo-haptischer Informationsverarbeitung. Die Aktivationsmuster bei audio-haptischer Stimulation deuteten auf Verarbeitung bilateral im temporo-parietalen Bereich hin in Temporallappen, Parietallappen und der Insula. Die Aktivierungen kommen vermutlich durch Feedforward-Projektionen und Konnektivität zwischen auditorischem und somatosensorischem Kortex zustande, in der Insula durch Konvergenz der auditorischen und somatosensorischen Was-Informationen. Trimodale Stimulation zeigte bei Anwendung des Max-Kriteriums, bei welchem die audio-visuo-haptische Aktivität stärker als die einzelnen unisensorischen Signalantworten ausfallen sollte, ein Areal im linken temporo-parietalen Bereich. Bei weniger strenger Auswertung wurde eine weitere Region im rechten Zerebellum nachgewiesen. Beide konnten der Erweiterung des Max-Kriteriums zum Vergleich zwischen tri- und bisensorischer Aktivität nicht standhalten. Beim Affen existiert eine superior temporale polysensorische Region, welche auf visuelle, auditorische und haptische Reize reagiert. Ob ein integratives trisensorisches Areal beim Menschen existiert, sollte in weiteren Studien untersucht werden. Vielleicht liegt eine ausgeprägte interindividuelle Variabilität der Lokalisation des Konvergenzpunktes vor. Eine andere Möglichkeit ist, dass die Verarbeitung im Gehirn vermehrt bisensorisch gegliedert verläuft. Um dies in zukünftigen Studien besser zu untersuchen, könnte es von Vorteil sein simple sensorische Stimuli zu verwenden. Eine Reizdegradierung hätte verminderte Signalamplituden zur Folge, was multisensorische Interaktionen mit nachfolgendem Signalanstieg besser beurteilen ließe. Darüber hinaus könnte in den Studien fMRT-Adaptation angewendet werden. Über die repetitive Stimulusdarbietung kommt es ebenfalls zu verminderter BOLD-Signalantwort. Die vorliegende Studie hat weiterhin die Notwendigkeit der Einführung von Kontrollbedingungen demonstriert. Neben unisensorischen sollten bisensorische Kontrollbedingungen zur Beurteilung trisensorischer Aktivität herangezogen werden. Eine Kontrollbedingung zur Beurteilung des Ruhezustandes ohne sensorischen Reiz sollte ebenfalls vorhanden sein. Prinzipiell scheint das Max-Kriterium zur Detektion multisensorischer Integration angemessen zu sein.The perception of our environment relies on information from the different sensory modalities which are processed in specialized brain regions and then integrated to form a coherent percept. How these processes take place and which operations lead to a coherent object perception are fundamental questions in the cognitive neurosciences. The aim of this study was to investigate the neural correlates of multisensory integration. We expected to confirm previous findings as well as to gain new insights into audio-haptic and audio-visuo-haptic integration. Furthermore it examined appropriate criteria for the evaluation of multisensory effects and focused on the role of an appropriate control condition. Sixteen subjects were scanned with fMRI during uni-, bi- and trimodal stimulation. The stimulation consisted of the presentation of black-and-white images of animals, animal voices and animal figures either in isolation or in different bi- or trimodal combinations. Furthermore there was a motor control condition without sensory input. The unisensory activations were located in the modality-specific cortices and mostly confirmed previous findings as well as the existence of the 'what' and 'where' pathways. Bimodal audio-visual stimulation elicited activations in the temporal lobe around the area of STS/STG which is highly relevant to the integration of audio-visual information. Activations in cingulate gyrus, fusiform gyrus and precuneus seem to occur when presenting familiar stimuli and congruent combinations. There were also audio-visual interactions in early visual and auditory conduction pathways. Visuo-haptic integration seems to take place in LOtv, IPS and the ventral cerebellum according to the present data. LOtv and IPS are probably involved in processing geometrical forms. The ventral cerebellum is activated through cortico-cerebellar circuits during visuo-haptic information processing. Audio-haptic stimulation revealed a bilateral temporo-parietal region located in-between the respective secondary and somatosensory cortices as well as the insula. Activations are probably attributable to feedforward projections and connectivity between auditory and somatosensory cortex. Auditory and somatosensory object information probably converges in the insula. Trimodal stimulation revealed activation in the left temporo-parietal region when applying the max-criterion which reveals areas responding more strongly to audio-visuo-haptic activation compared to each of the unisensory signals. Another area was identified in the right cerebellum when applying more liberal criteria. Both regions did not fulfill the extension of the max criterion to a comparison of the trisensory versus bisensory activations. Further studies are required to test whether a trisensory integration region, which has been found in simians, also exists in humans. Maybe there is a distinct interindividual variability in the localization of such a convergence site. Another possibility might be that cortical processing is based mainly on bisensory integration. To explore this in future studies it might be helpful to use more low-level stimulus material. A reduction of sensory input could lead to smaller signal amplitudes which would facilitate the interpretation of multisensory interactions. In addition the application of fMRI adaptation could be useful. Repeated stimulus presentation results in reductions of BOLD signals as well. The present study has demonstrated the need for appropriate control conditions. Trisensory activity should be compared to unisensory as well as bisensory control tasks to assess the result pattern. Stimulation conditions should be contrasted with control conditions without sensory input. It seems as if the max-criterion is suitable to investigate multisensory integration

The ‘Faust’ or ’Lucifer’ Sonata? On Liszt’s idea of programme music as exemplified by his Piano Sonata in B minor

The musicological tradition places Liszt’s Sonata in B minor within the sphere of compositions inspired by the Faustian myth. Its musical material, its structure and its narrative exhibit certain similarities to the ‘Faust’ Symphony. Yet there has appeared a different and, one may say, a rival interpretation of Sonata in B minor. What is more, it is well-documented from both a musical and a historical point of view. It has been presented by Hungarian pianist and musicologist Tibor Szasz. He proposes the thesis that the Sonata in B minor has been in fact inspired by Milton’s Paradise Lost, with its three protagonists: Adam, Satan and Christ. He finds their illustrations and even some key elements of the plot in the Sonata’s narrative. But yet Milton’s Paradise Lost and Goethe’s Faust are both stories of the Fall and Salvation, of the cosmic struggle between good and evil. The triads of their protagonists - Adam and Eve, Satan, and Christ; Faust, Mephisto and Gretchen - are homological. Thus both interpretations of the Sonata, the Goethean and the Miltonian, or, in other words, the Faustian and the Luciferian, are parallel and complementary rather than rival. It is also highly probable that both have had their impact on the genesis of the Sonata in B minor

The ‘Faust’ or ’Lucifer’ Sonata? On Liszt’s idea of programme music as exemplifi ed by his Piano Sonata in B minor

The musicological tradition places Liszt’s Sonata in B minor within the sphere of compositions inspired by the Faustian myth. Its musical material, its structure and its narrative exhibit certain similarities to the ‘Faust’ Symphony. Yet there has appeared a diff erent and, one may say, a rival interpretation of Sonata in B minor. What is more, it is well-documented from both a musical and a historical point of view. It has been presented by Hungarian pianist and musicologist Tibor Szász. He proposes the thesis that the Sonata in B minor has been in fact inspired by Milton’s Paradise Lost, with its three protagonists: Adam, Satan and Christ. He fi nds their illustrations and even some key elements of the plot in the Sonata’s narrative. But yet Milton’s Paradise Lost and Goethe’s Faust are both stories of the Fall and Salvation, of the cosmic struggle between good and evil. The triads of their protagonists – Adam and Eve, Satan, and Christ; Faust, Mephisto and Gretchen – are homological. Thus both interpretations of the Sonata, the Goethean and the Miltonian, or, in other words, the Faustian and the Luciferian, are parallel and complementary rather than rival. It is also highly probable that both have had their impact on the genesis of the Sonata in B minor

A mikrobiom szerepe a fül-orr-gégészetben = The role of the microbiome in otorhinolaryngology

Absztrakt: Egészségünket a szervezetünkben és a bőrünkön élő sokszínű mikrobaközösség jelentősen meghatározza. A normálflóra tagjai közötti egyensúly elengedhetetlen az egészség fenntartásában. Az újgenerációs szekvenálás gyors, szenzitív módszer, amely a mikrobiom egészének vizsgálatára alkalmas előzetes hipotézis nélkül, és információt ad a rezisztenciáról és a virulenciáról is. Ennek a módszernek a segítségével lehetővé vált betegségekben a patogén baktériumok, illetve az ezek szaporodását gátló, úgynevezett protektív baktériumok azonosítása. A mikrobiom változásainak feltérképezése segít új terápiás célpontok meghatározásában és az antibiotikumok célzott kiválasztásában. Széles spektrumú antibiotikum használatakor a normálflóra hasznos tagjai is kipusztulnak, ami visszatérő vagy krónikussá váló fertőzések kialakulásához vezet. A fül-orr-gégészeti infekciók a leggyakoribb fertőző betegségek az emberi szervezetben és az antibiotikum alkalmazásának vezető okai világszerte. Az egészséges emberben, illetve a fül-orr-gégészeti betegségekben előforduló baktérium-összetétellel kapcsolatban számos molekuláris biológiai vizsgálat történt az utóbbi években. A szerzők ismertetik az egyes fül-orr-gégészeti anatómiai régiók normálflórájának tagjait, és különböző patológiás állapotokban a baktérium-összetétel változásait is összefoglalják. Orv Hetil. 2019; 160(39): 1533–1541. | Abstract: Our health is highly determined by the diverse microbial community living within our body and upon our skin. Balance among the members of the commensal microbiota is essential for the preservation of health. New generation sequencing is a rapid, sensitive method for determining the whole microbiome without prior hypothesis and also gives information on the resistance and virulence status. Application of this method can help to identify the pathogens contributing to different diseases, and also the protective bacteria inhibiting their growth. Detecting the changes of the microbiome helps to identify new therapeutic targets and establish targeted antibiotic therapy. Broad-spectrum antibiotics also act against the beneficial members of the microbial flora, which may lead to the development of recurrent or chronic disease. Ear, nose and throat infections are the most common infective diseases in humans and the leading cause for antibiotic prescription worldwide. In recent years, many studies using molecular biology methods were performed examining the microbiome of healthy humans and in otorhinolaryngologic diseases. In the present work, the authors review the changes of the microbiological communities in the healthy state and in various pathologic states in the anatomic regions of the ear, nose and throat. Orv Hetil. 2019; 160(39): 1533–1541

A musculus tensor tympani és a musculus stapedius ín átvágásának hatása a Ménière-betegségben szenvedők életminőségére = Effect of the stapedius and tensor tympani muscles tenotomy on the quality of life of patients suffering from Ménière’s disease

Absztrakt: Bevezetés: A musculus (m.) stapedius és a m. tensor tympani (TT) inának átvágása egy minimálinvazív sebészi lehetőség a Ménière-betegség sebészi terápiájában. A feltételezett hatásmechanizmus szerint a tensor tympani medializálja a stapest az ovális ablakban, és ennek, valamint a stapediusínnak az átvágása befolyásolja a belső fül nyomásviszonyait Ménière-betegségben. Célkitűzés: Dizziness Handicap Inventory (DHI) – szédülésterheltségi skála – és Tinnitus Handicap Inventory (THI) – fülzúgásterheltségi skála – segítségével annak megállapítása, hogy a tenotomia hogyan befolyásolja a Ménière-betegek életminőségét. Módszer: Diagnosztizált, egyoldali Ménière-betegeket vizsgáltunk (22 beteg), akik előzetes beleegyezésük után tenotomia műtéten estek át, általános vagy helyi érzéstelenítésben. A betegek a műtét előtt, a műtét után 3 hónappal és egy évvel töltöttek ki kérdőívet, és beszámoltak betegségük tüneteiről. Statisztikai analízis: A statisztikai analízis az IBM SPSS V24-es programmal készült. Mivel a vizsgált paraméterek nem mutattak normáleloszlást, nemparametrikus tesztet (Mann–Whitney-féle U-teszt) alkalmaztunk. Szignifikanciaszintnek minden esetben a p<0,05 értéket tekintettük. Eredmények: A DHI-értékek minden betegben szignifikánsan csökkentek, azaz életminőségük jelentősen javult. Elmondásuk szerint szédüléses rohamaik ritkábbá váltak, rövidültek. A fülzúgás szignifikánsan csökkent. Minden beteg állapotjavulásról számolt be. Következtetés: Bár a műtét hatásának patomechanizmusa (a stapes medializációjának csökkenése az ovális ablakban) nem teljesen tisztázott, és az utánkövetési idő sem hosszú, a rohamok súlyosságának csökkentésével a tenotomia ígéretes, minimálinvazív sebészi lehetőségnek tűnik a konzervatív terápiára rezisztens, Ménière-betegségben szenvedő betegek életminőségének javításában. Orv Hetil. 2020; 161(5): 177–182. | Abstract: Introduction: Tenotomy of the tendon of the stapedius and tensor tympani (TT) muscles is a minimal-invasive surgical therapeutic procedure in Ménière’s disease (MD). It has been assumed that the TT medializes the stapes into the oval window, resulting in changes in perilymphatic pressures of the inner ear. By cutting the tendons of both middle ear muscles, they affect the pressure dynamics by not augmenting this pressure even further. Aim: The immediate and long-term investigation of the effect of middle ear muscle tenotomy on the quality of life of patients suffering from Ménière’s disease, measured by the Dizziness Handicap Inventory (DHI) and the Tinnitus Handicap Inventory (THI). Method: A follow-up study of 22 patients with definite, unilateral Ménière’s disease had undergone tenotomy under general or local anesthesia through an endaural approach. Pre- and postoperative DHI values were compared for all patients. Statistical analysis: The statistical analysis was completed by using the IBM SPSS V24 software. Since the parameters did not show normal distribution, non-parametric test (Mann–Whitney U test) was used. The significance level was specified as p<0.05. Results: A statistically significant reduction of DHI scores was noted in all patients. The tinnitus significantly reduced and all of the patients mentioned improved symptoms of MD. Conclusion: Although the follow-up period is short, and the pathomechanism (decrease of stapes medialization in the oval window) is not exactly clear, tenotomy seems to be a successful promising surgical treatment method with a high reduction of dizziness handicap score in conservative therapy-resistant Ménière’s disease. Orv Hetil. 2020; 161(5): 177–182

Patient delay and its clinical significance among head and neck cancer patients in Hungary

Introduction: Head and neck cancers represent a major health problem in Hungary. With their high incidence and mortality rates, Hungary is one of the world leaders in these indicators. The length of patient delay, defined as time from onset of symptoms to first medical consultation, is unknown in Hungarian patients with head and neck cancer. We aimed to use a representative sample of the Hungarian head and neck cancer patient population to determine patient delay according to disease localization and stage and to identify correlations with other clinical parameters.Methods: In our retrospective study, we reviewed patient documentation. For the inclusion, the patients had to be diagnosed with malignant tumors of the oral cavity, oropharynx, hypopharynx or larynx at the Department Head and Neck Surgery of Semmelweis University between 2012 and 2017.Results: We identified 236 patients who met the inclusion criteria. The median delay was 9.5 weeks (range 0–209 weeks) and the mean delay of patients was 17.57 weeks (SD 23.67). There was a significant difference in patient delay data by location. Among glottic cancers, the most common diagnosis was an early stage (67%), compared with other localizations, including most commonly the oropharynx (81%) and hypopharynx (80%), where a locoregionally advanced stage was more frequent.Discussion: Compared to data from different countries, the delay of Hungarian patients with head and neck cancer is significantly longer, which may contribute to the high mortality in Hungary. Screening and patient education in high-risk groups could contribute to earlier diagnosis and thus improve prognosis

Anti-PD-1 Therapy Does Not Influence Hearing Ability in the Most Sensitive Frequency Range, but Mitigates Outer Hair Cell Loss in the Basal Cochlear Region

The administration of immune checkpoint inhibitors (ICIs) often leads to immune-related adverse events. However, their effect on auditory function is largely unexplored. Thorough preclinical studies have not been published yet, only sporadic cases and pharmacovigilance reports suggest their significance. Here we investigated the effect of anti-PD-1 antibody treatment (4 weeks, intraperitoneally, 200 μg/mouse, 3 times/week) on hearing function and cochlear morphology in C57BL/6J mice. ICI treatment did not influence the hearing thresholds in click or tone burst stimuli at 4-32 kHz frequencies measured by auditory brainstem response. The number and morphology of spiral ganglion neurons were unaltered in all cochlear turns. The apical-middle turns (32 kHz). The number of Iba1-positive macrophages has also increased moderately in this high frequency region. We conclude that a 4-week long ICI treatment does not affect functional and morphological integrity of the inner ear in the most relevant hearing range (4-32 kHz; apical-middle turns), but a noticeable preservation of OHCs and an increase in macrophage activity appeared in the >32 kHz basal part of the cochlea