Frequency division multiplexing for interferometric planar Doppler velocimetry

A new method of acquiring simultaneously the signal and reference channels used for interferometric planar Doppler velocimetry is proposed and demonstrated. The technique uses frequency division multiplexing (FDM) to facilitate the capture of the requisite images on a single camera, and is suitable for time-averaged flow measurements. Furthermore, the approach has the potential to be expanded to allow the multiplexing of additional measurement channels for multicomponent velocity measurement. The use of FDM for interferometric referencing is demonstrated experimentally with measurements of a single velocity component of a seeded axisymmetric air jet. The expansion of the technique to include multiple velocity components was then investigated theoretically and experimentally to account for bandwidth, crosstalk, and dynamic range limitations. The technique offers reduced camera noise, automatic background light suppression, and crosstalk levels of typically <10%. Furthermore, as this crosstalk is dependent upon the channel modulations applied, it can be corrected for in postprocessing

The Timing of Feedback to Early Visual Cortex in the Perception of Long-Range Apparent Motion

When 2 visual stimuli are presented one after another in different locations, they are often perceived as one, but moving object. Feedback from area human motion complex hMT/V5+ to V1 has been hypothesized to play an important role in this illusory perception of motion. We measured event-related responses to illusory motion stimuli of varying apparent motion (AM) content and retinal location using Electroencephalography. Detectable cortical stimulus processing started around 60-ms poststimulus in area V1. This component was insensitive to AM content and sequential stimulus presentation. Sensitivity to AM content was observed starting around 90 ms post the second stimulus of a sequence and most likely originated in area hMT/V5+. This AM sensitive response was insensitive to retinal stimulus position. The stimulus sequence related response started to be sensitive to retinal stimulus position at a longer latency of 110 ms. We interpret our findings as evidence for feedback from area hMT/V5+ or a related motion processing area to early visual cortices (V1, V2, V3)

Source localization of the P300 using a combination of EEG and fMRI

Das ereigniskorrelierte Potential (EKP) P300 ist eines der am häufigsten untersuchten Potentiale des Elektroenzephalogramms (EEG). Wegen der bedeutsamen Rolle der P300 in der kognitiven Forschung mit gesunden Probanden und psychiatrischen Patienten kommt der Suche nach ihren neuronalen Generatoren ein hoher Stellenwert zu. Man geht im Allgemeinen davon aus, dass sie kein einheitliches Potential darstellt und von mehreren weit verstreuten Quellen generiert wird. Die Fragen nach der genauen Anzahl der P300-Subkomponenten, ihrer Lokalisierung sowie den ihnen zugrunde liegenden kognitiven Prozesse sind jedoch nach wie vor ungelöst. Die Zielsetzung der vorliegenden Arbeit war, die P300 mit Hilfe der Kombination vom EEG und der funktionalen Magnetresonanztomografie (fMRT) in ihre Subkomponenten zu untergliedern und deren Quellen zu lokalisieren. Zu diesem Zweck wurden drei kombinierte EEG/fMRT-Studien durchgeführt. Die ersten beiden Studien beinhalten eine abgewandelte Form des klassischen Oddballparadigmas. Bei der dritten Studie handelt es sich um ein Arbeitsgedächtnisexperiment. Durch die Verknüpfung der fMRT-Ergebnisse mit EKP-Daten aus den beiden Oddball-Experimenten konnten die neuronalen Quellen der zwei wichtigsten Subkomponenten der P300, der P3a und P3b, lokalisiert werden. Es konnte gezeigt werden, dass inferiore und posteriore parietale (IPL bzw. PPC) und inferior temporale (IT) Areale zur Entstehung der P3b beitrugen, während hauptsächlich die präzentralen Regionen (PrCS) die P3a generierten. Die Ergebnisse des Arbeitsgedächtnisexperiments bestätigten die P3b-Quellenlokalisierung der Oddball-Untersuchung mit einr Beteiligung von PPC und IT an der Generierung der P3b-Komponente. Das Arbeitsgedächtnisexperiment verdeutlichte aber auch, dass eine komplexere Abrufanforderung (mit langen Reaktionszeiten) zu einer anhaltenden Aktivität im PPC und einer späten Antwort im ventrolateralen präfrontalen Kortex (VLPFC) führte, die eine zweite P3b-Subkomponente generierten. Durch eine umfassende zeitlich-räumliche Trennung der neuronalen Aktivität beim Arbeitsgedächtnisabruf konnten darüber hinaus die einzelnen Stufen der beteiligten Informationsverarbeitungsprozesse (mentale Chronometrie) beschrieben werden. Diese Anwendung ging über die „reine“ Quellenlokalisation der P300-Komponenten hinaus. Die Ergebnisse zeigten frühe transiente Aktivierungen im IT, die sich zeitlich mit dem Beginn einer anhaltenden Aktivität im PPC überlappten. Darüber hinaus wurden eine späte transiente Aktivität im VLPFC und eine späte anhaltende Aktivität im medialen frontalen und motorischen Kortex (MFC bzw. MC) beobachtet. Es liegt nahe, dass diese neuronalen Signaturen einzelne Stufen kognitiver Aufgabenverarbeitungsschritte wie Reizevaluation (IT), Operationen am Gedächtnispuffer (PPC), aktiven Abruf (VLPFC) und Reaktionsorganisation (MFC und MC) reflektieren. Die vorgestellten Quellenmodelle zeigten übereinstimmend, dass mehrere kortikale Generatoren das P300-EKP erzeugen. Dabei trugen neben den erwarteten parietalen interessanterweise auch inferior temporale und inferior frontale Quellen zur P3b bei, während die P3a vor allem auf anterioren Generatoren im prämotorischen Kortex basierte. Diese Ergebnisse bestätigen teilweise die bisherigen Lokalisationsmodelle, die weitgehend auf neuropsychologischen und invasiven neurophysiologischen Befunden beruhen, widersprechen ihnen aber auch zum Teil, besonders was die Abwesenheit der postulierten präfrontalen und hippocampalen Beiträge zur P3a bzw. P3b betrifft.The P300 event-related potential (ERP) is one of the most studied potentials of the electroencephalogram (EEG). Because of its prominent role in studies of cognition both in healthy individuals and patients, the elucidation of its neural generators is of considerable interest. It has been proposed that the P300 is not a unitary component but generated by several widespread sources. However, the identification of the exact number and localization of its subcomponents and of the related cognitive processes has remained controversial. The aim of the present work was to decompose the P300 in its underlying subcomponents and to localize their neuronal sources using three combined EEG and functional magnetic resonance imaging (fMRI) studies. The first two investigations employed a modified version of the classical “oddball” paradigm while the third study was a working memory experiment. The neuronal sources of the two main P300 subcomponents, namely the P3a and P3b, were localized by integrating the fMRI results with the ERP data in both oddball tasks. I was able to show that inferior and posterior parietal (IPL and PPC, respectively) and inferior temporal (IT) areas contributed to P3b generation, whereas the precentral regions (PrCS) mainly accounted for the P3a component. The working memory experiment confirmed the finding of P3b generators in IT and PPC obtained in the oddball studies. Moreover, the more complex working memory task with longer reaction times demonstrated that the sustained PPC and late VLPFC source activities generated a second subcomponent of the P3b complex. The present comprehensive temporo-spatial decomposition of the neuronal activity in this study provided additional information about the processing stages (mental chronometry) involved in working memory retrieval. This approach goes beyond a “simple” source localization of distinct P300 subcomponents. The analysis revealed an early transient activation of IT, which coincided with the onset of a sustained PPC activation. Furthermore we observed late transient responses in VLPFC and late sustained activity both in medial frontal (MFC) and premotor areas (MC). I have proposed that these neural signatures reflect the following cognitive stages of task processing: perceptual evaluation (inferotemporal cortex), storage buffer operations (PPC), active retrieval (VLPFC), and action selection (MFC and MC). This is also supported by the differential temporal contribution of these activations to specific subcomponents of the P300 cognitive potential. These results support the idea that the P300 ERP is the result of the activity of cortical generators that are widely distributed in time and space. Interestingly, beside the expected parietal sources, the fMRI-constrained source analysis revealed that higher visual areas contributed to the P3b, whereas the P3a was basically generated in premotor cortex. The present results have partially confirmed the previous localization models of the P300 which were based mainly on neuropsychological and invasive neurophysiological evidence. However, our findings contradict the assumed contribution of prefrontal cortex and hippocampus to the generation of P3a and P3b, respectively

Vom neuronalen Einzelfahrschein zur kortikalen Netzkarte : audio-visuelle Objekterkennung in der Großhirnrinde

Die Wahrnehmung von Objekten gelingt uns jeden Tag unzählige Male – zumeist rasend schnell und problemlos. Obwohl fast immer mehrere unserer Sinne gleichzeitig bei ihrer Wahrnehmung angesprochen werden, erscheinen uns diese Objekte dennoch als ganzheitlich und geschlossen. Für die neuronale Verarbeitung eines bellenden Hundes zum Beispiel empfängt die Großhirnrinde zumindest Eingangsdaten des Seh- und des Hörsystems. Sie werden auf getrennten Pfaden und in spezialisierten Arealen mit aufsteigender Komplexität analysiert. Dieses Funktionsprinzip der parallel verteilten Verarbeitung stellt die Wissenschaftler aber auch vor das so genannte »Bindungsproblem«: Wo und wie werden die Details wieder zu einem Ganzen – zu einer neuronalen Repräsentation – zusammengefügt? Am Institut für medizinische Psychologie der Universitätsklinik Frankfurt untersuchen Neurokognitionsforscher die crossmodale Objekterkennung mit einer Kombination modernster Verfahren der Hirnforschung und kommen dabei den Ver - arbeitungspfaden in der Großhirnrinde auf die Spur

A psychophysiology practical as part of the medical psychology course

Die Vermittlung der Zusammenhänge zwischen psychologischen Funktionen und körperlichen Veränderungen sowie deren Relevanz für die Entstehung und Aufrechterhaltung von Krankheiten stellt ein zentrales Ziel der Ausbildung in Medizinischer Psychologie dar. Zur Veranschaulichung dieser Zusammenhänge führten wir ein Psychophysiologie-Praktikum im ersten vorklinischen Semester ein. Die Studierenden führten in Vierergruppen mit Hilfe ausführlicher schriftlicher Instruktionen jeweils ca. 30 Minuten andauernde praktische Übungen durch, die die folgenden Themen behandelten: (1) Stress (abhängige Variable: Herzrate), (2) "Lügendetektor" (abhängige Variable: Hautleitwertsreaktionen), (3) Biofeedback (abhängige Variable: Hauttemperatur) und (4) Elektroenzephalogramm (abhängige Variable: Amplituden der vier klassischen Frequenzbänder). Die praktischen Übungen wurden durch theoretische Gruppenarbeiten und einen Termin zur Zusammenfassung der Ergebnisse der Übungen ergänzt. Die studentische Evaluation des Praktikums war durchweg positiv. So wurde das Praktikum als Bereicherung des Kurses angesehen, und der selbstbeurteilte Kenntnisstand auf dem Gebiet der Psychophysiologie zeigte eine signifikante Verbesserung. Diese Ergebnisse sowie unsere Eindrücke während des Praktikums bekräftigten unseren Entschluss, ein Psychophysiologie-Praktikum als Teil des Kurses der Medizinischen Psychologie und Medizinischen Soziologie fest zu etablieren.Teaching in medical psychology aims at establishing an understanding of the relationships between psychological functions and bodily reactions and of the relevance of these interactions for the development and maintenance of diseases. To illustrate these relationships, a psychophysiology practical was introduced in the first semester. Students performed practical 30-minute exercises in groups of four on the basis of comprehensive written instructions. The following topics were covered: (1) stress (dependent variable: heart rate), (2) "lie detection" (dependent variable: skin conductance response), (3) biofeedback (dependent variable: skin temperature), and (4) electroencephalogram (dependent variable: amplitude in the four classical frequency bands). The practical exercises were complemented by theoretical group work and a summary of the results of the exercises. Students evaluated the practical positively. It was considered a benefit to the course, and the self-rated knowledge in the area of psychophysiology increased significantly. These results, as well as our experiences during the practical, have reinforced our decision to establish a psychophysiology practical as part of the medical psychology/medical sociology course

Interference between items stored for distinct tasks in visual working memory

The action perspective on working memory suggests that memory representations are coded according to their specific temporal and behavioral task demands. This stands in contrast to theories that assume representations are stored in a task-agnostic format within a “common workspace”. Here, we tested whether visual items that are memorized for different tasks are stored separately from one another or show evidence of inter-item interference during concurrent maintenance, indicating a common storage. In two experiments, we combined a framing memory task (memorize a motion direction for continuous direction report) with an embedded memory task (memorize a motion direction for a binary direction discrimination) that was placed within the retention period of the framing task. Even though the temporal and action demands were item specific, we observed two types of interference effects between the items: The embedded motion direction was (1) repulsed away and (2) degraded in precision by the motion direction of the item in the framing task. Repulsion and precision degradation increased with item similarity when both items were concurrently held in working memory. In contrast, perceptual and iconic memory control conditions revealed weaker repulsion overall and no interference effect on precision during the stimulus processing stages prior to working memory consolidation. Thus, additional inter-item interference arose uniquely within working memory. Together, our results present evidence that items that are stored for distinct tasks to be performed at distinct points in time, reside in a common workspace in working memory

Development of Reporter Systems of Cellular Readouts of Chinese Hamster Ovary (CHO) Cells

Biological stress is perceived and occurs across all cellular organisms. When cells undergo or perceive changes in homeostasis, such as temperature fluctuations, changes in pH/ pressure or oxidative stress, cellular responses are initiated that results in the production of various molecular players to relieve the stress. Different types of stresses cause the specific initiation of diverse molecular pathways and elements to counter the cellular stress. Such stress is perceived in in vitro cultured mammalian cells, such as Chinese hamster ovary (CHO) cells when they are grown in culture to produce secreted biotherapeutic proteins. The perception of different stresses can limit the yield of biotherapeutic protein produced and/or the quality of the protein from such cells. Here, genetic reporter systems that can report on the perception of such stresses have been designed for use in CHO cells during production of biopharmaceuticals so that strategies to prevent or harness such stresses can be developed to enhance recombinant protein production from such cell systems. A major controlling factor in responding to and combating these cellular stresses begins at the transcriptional level, by the activation of transcription factors (TF), and their complementary DNA binding motifs that regulate gene transcription. The goal of the work presented here was to harness transcription factor binding sites upstream of promoters driving the expression of reporter genes in mammalian cells culture whereby the expression of the fluorescence reporter proteins would provide a real time readout of cellular stress perception that the targeted transcription factor is involved in controlling. Using previously reported transcription factor motif sequences, cloning them into a plasmid vector with selected promoter regions, and multiple cloning sites, reporter gene constructs were developed. A destabilized GFP reporter system was used as the readout as the rapid turnover of this gives a more accurate representation of the current stress perception rather than a historical readout. The reporter constructs were designed, assembled and successfully cloned. The specific stresses and binding sequences utilised targeted transcription factors that were activated upon ER, energy, lipid and oxidative stress. Transfections of a selection of the constructs was then undertaken into CHO-S mammalian cells to establish baseline expression from the reporter constructs as determined by flow cytometry analysis of GFP fluorescence. In particular, carbohydrate response element (ChoRE, energy stress response) and fatty acid stress response (Peroxisome Proliferator-Activated Receptor, PPAR) transcription factor binding sequence containing constructs were transfected and investigated under spent media and oxidative stress conditions. However, under these harsh environmental conditions there was low culture viability and reporter gene expression levels. A further set of transfections were undertaken with the ER stress response (ERSE) TF containing motifs, with varying constructs evaluated that contained different elements, sequence lengths and promotor regions. The cellular external conditions were not altered from the CHO-S maintenance media, and differences in reporter gene expression from these were detected. In conclusion, a toolbox of reporter gene constructs that allow the monitoring in real time of specific stresses on mammalian cells during culture have been designed and developed and some of these have had preliminary validation undertaken. Further analyses can be performed with these under stress conditions to continue to validate and develop a toolbox of stress reporter systems. The potential application of these in CHO cells during the development of cells and bioprocesses for the production of secreted biotherapeutic proteins may help define when such cells perceive different stresses that might limit recombinant protein product yields and quality, allowing the development of systems and processes that can either limit or utilise these responses to further enhance the productivity and quality of product from these cell expression systems

Visual Target Modulation of Functional Connectivity Networks Revealed by Self-Organizing Group ICA

We applied a data-driven analysis based on self-organizing group independent component analysis (sogICA) to fMRI data from a three-stimulus visual oddball task. SogICA is particularly suited to the investigation of the underlying functional connectivity and does not rely on a predefined model of the experiment, which overcomes some of the limitations of hypothesis-driven analysis. Unlike most previous applications of ICA in functional imaging, our approach allows the analysis of the data at the group level, which is of particular interest in high order cognitive studies. SogICA is based on the hierarchical clustering of spatially similar independent components, derived from single subject decompositions. We identified four main clusters of components, centered on the posterior cingulate, bilateral insula, bilateral prefrontal cortex, and right posterior parietal and prefrontal cortex, consistently across all participants. Post hoc comparison of time courses revealed that insula, prefrontal cortex and right fronto-parietal components showed higher activity for targets than for distractors. Activation for distractors was higher in the posterior cingulate cortex, where deactivation was observed for targets. While our results conform to previous neuroimaging studies, they also complement conventional results by showing functional connectivity networks with unique contributions to the task that were consistent across subjects. SogICA can thus be used to probe functional networks of active cognitive tasks at the group-level and can provide additional insights to generate new hypotheses for further study

Neural Signatures of Stimulus Features in Visual Working Memory—A Spatiotemporal Approach

We examined the neural signatures of stimulus features in visual working memory (WM) by integrating functional magnetic resonance imaging (fMRI) and event-related potential data recorded during mental manipulation of colors, rotation angles, and color–angle conjunctions. The N200, negative slow wave, and P3b were modulated by the information content of WM, and an fMRI-constrained source model revealed a progression in neural activity from posterior visual areas to higher order areas in the ventral and dorsal processing streams. Color processing was associated with activity in inferior frontal gyrus during encoding and retrieval, whereas angle processing involved right parietal regions during the delay interval. WM for color–angle conjunctions did not involve any additional neural processes. The finding that different patterns of brain activity underlie WM for color and spatial information is consistent with ideas that the ventral/dorsal “what/where” segregation of perceptual processing influences WM organization. The absence of characteristic signatures of conjunction-related brain activity, which was generally intermediate between the 2 single conditions, suggests that conjunction judgments are based on the coordinated activity of these 2 streams