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

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

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

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

Basic operations in working memory: contributions from functional imaging studies. Behav Brain Res

a b s t r a c t Working memory (WM) constitutes a fundamental aspect of human cognition. It refers to the ability to keep information active for further use, while allowing it to be prioritized, modified and protected from interference. Much research has addressed the storage function of WM, however, its 'working' aspect still remains underspecified. Many operations that work on the contents of WM do not appear specific to WM. The present review focuses on those operations that we consider "basic" because they operate in the service of memory itself, by providing its basic functionality of retaining information active, in a stable yet flexible way. Based on current process models of WM we review five strands of research: (1) mnemonic selection of one item amongst others, (2) updating the focus of attention with the selected item, (3) updating the content of visual WM with new item(s), (4) rehearsal of visuospatial information and (5) coping with interference. We discuss the neuronal substrates underlying those operations obtained with functional magnetic resonance imaging and relate them to findings on "executive functions". The presented data support the view that WM emerges from interactions between higher sensory, attentional and mnemonic functions, with separable neural bases. However, interference processing and the representation of rule switching in WM may demand an extension of the current WM models by executive control functions

Object-based attention prioritizes working memory contents at a theta rhythm

Attention selects relevant information regardless of whether it is physically present or internally stored in working memory. Perceptual research has shown that attentional selection of external information is better conceived as rhythmic prioritization than as stable allocation. Here we tested this principle using information processing of internal representations held in working memory. Participants memorized 4 spatial positions that formed the end points of 2 objects. One of the positions was cued for a delayed match–nonmatch test. When uncued positions were probed, participants responded faster to uncued positions located on the same object as the cued position than to those located on the other object, revealing object-based attention in working memory. Manipulating the interval between cue and probe at a high temporal resolution revealed that reaction times oscillated at a theta rhythm of 6 Hz. Moreover, oscillations showed an antiphase relationship between memorized but uncued positions on the same versus other object as the cued position, suggesting that attentional prioritization fluctuated rhythmically in an object-based manner. Our results demonstrate the highly rhythmic nature of attentional selection in working memory. Moreover, the striking similarity between rhythmic attentional selection of mental representations and perceptual information suggests that attentional oscillations are a general mechanism of information processing in human cognition. These findings have important implications for current, attention-based models of working memory

Object-based attention prioritizes working memory contents at a theta rhythm

Attention selects relevant information regardless of whether it is physically present or internally stored in working memory. Perceptual research has shown that attentional selection of external information is better conceived as rhythmic prioritization than as stable allocation. Here we tested this principle using information processing of internal representations held in working memory. Participants memorized four spatial positions that formed the endpoints of two objects. One of the positions was cued for a delayed match-non-match test. When uncued positions were probed, participants responded faster to uncued positions located on the same object as the cued position than to those located on the other object, revealing object-based attention in working memory. Manipulating the interval between cue and probe at a high temporal resolution revealed that reaction times oscillated at a theta rhythm of 6 Hz. Moreover, oscillations showed an anti-phase relationship between memorized but uncued positions on the same versus other object as the cued position, suggesting that attentional prioritization fluctuated rhythmically in an object-based manner. Our results demonstrate the highly rhythmic nature of attentional selection in working memory. Moreover, the striking similarity between rhythmic attentional selection of mental representations and perceptual information suggests that attentional oscillations are a general mechanism of information processing in human cognition. These findings have important implications for current, attention-based models of working memory

Decoding spatial versus non-spatial processing in auditory working memory

Objective: Research on visual working memory has shown that individual stimulus features are processed in both specialized sensory regions and higher cortical areas. Much less evidence exists for auditory working memory. Here, a main distinction has been proposed between the processing of spatial and non-spatial sound features. Our aim was to examine feature-specific activation patterns in auditory working memory. Methods: We collected fMRI data while 28 healthy adults performed an auditory delayed match-to-sample task. Stimuli were abstract sounds characterized by both spatial and non-spatial information, i.e., interaural time delay and central frequency, respectively. In separate recording blocks, subjects had to memorize either the spatial or non-spatial feature, which had to be compared with a probe sound presented after a short delay. We performed both univariate and multivariate comparisons between spatial and non-spatial task blocks. Results: Processing of spatial sound features elicited a higher activity in a small cluster in the superior parietal lobe than did sound pattern processing, whereas there was no significant activation difference for the opposite contrast. The multivariate analysis was applied using a whole-brain searchlight approach to identify feature-selective processing. The task-relevant auditory feature could be decoded from multiple brain regions including the auditory cortex, posterior temporal cortex, middle occipital gyrus, and extended parietal and frontal regions. Conclusion: In summary, the lack of large univariate activation differences between spatial and non-spatial processing could be attributable to the identical stimulation in both tasks. In contrast, the whole-brain multivariate analysis identified feature-specific activation patterns in widespread cortical regions. This suggests that areas beyond the auditory dorsal and ventral streams contribute to working memory processing of auditory stimulus features