Neuronal Generator Patterns At Scalp Elicited By Lateralized Aversive Pictures Reveal Consecutive Stages Of Motivated Attention

Event-related potential (ERP) studies have provided evidence for an allocation of attentional resources to enhance perceptual processing of motivationally salient stimuli. Emotional modulation affects several consecutive components associated with stages of affective-cognitive processing, beginning as early as 100–200 ms after stimulus onset. In agreement with the notion that the right parietotemporal region is critically involved during the perception of arousing affective stimuli, some ERP studies have reported asymmetric emotional ERP effects. However, it is difficult to separate emotional from non-emotional effects because differences in stimulus content unrelated to affective salience or task demands may also be associated with lateralized function or promote cognitive processing. Other concerns pertain to the operational definition and statistical independence of ERP component measures, their dependence on an EEG reference, and spatial smearing due to volume conduction, all of which impede the identification of distinct scalp activation patterns associated with affective processing. Building on prior research using a visual half-field paradigm with highly controlled emotional stimuli (pictures of cosmetic surgery patients showing disordered [negative] or healed [neutral] facial areas before or after treatment), 72channel ERPs recorded from 152 individuals (ages 13–68 years; 81 female) were transformed into reference-free current source density (CSD) waveforms and submitted to temporal principal components analysis (PCA) to identify their underlying neuronal generator patterns. Using both nonparametric randomization tests and repeated measures ANOVA, robust effects of emotional content were found over parietooccipital regions for CSD factors corresponding to N2 sink (212 ms peak latency), P3 source (385 ms) and a late centroparietal source (630 ms), all indicative of greater positivity for negative than neutral stimuli. For the N2 sink, emotional effects were right-lateralized and modulated by hemifield, with larger amplitude and asymmetry for left hemifield (right hemisphere) presentations. For all three factors, more positive amplitudes at parietooccipital sites were associated with increased ratings of negative valence and greater arousal. Distributed inverse solutions of the CSDPCA-based emotional effects implicated a sequence of maximal activations in right occipitotemporal cortex, bilateral posterior cingulate cortex, and bilateral inferior temporal cortex. These findings are consistent with hierarchical activations of the ventral visual pathway reflecting subsequent processing stages in response to motivationally salient stimuli

Motivated Attention And Family Risk For Depression: Neuronal Generator Patterns At Scalp Elicited By Lateralized Aversive Pictures Reveal Blunted Emotional Responsivity

Behavioral and electrophysiologic evidence suggests that major depression (MDD) involves right parietotemporal dysfunction, a region activated by arousing affective stimuli. Building on prior event-related potential (ERP) findings (Kayser et al. 2016 NeuroImage 142:337–350), this study examined whether these abnormalities also characterize individuals at clinical high risk for MDD. We systematically explored the impact of family risk status and personal history of depression and anxiety on three distinct stages of emotional processing comprising the late positive potential (LPP). ERPs (72 channels) were recorded from 74 high and 53 low risk individuals (age 13–59 years, 58 male) during a visual half-field paradigm using highly-controlled pictures of cosmetic surgery patients showing disordered (negative) or healed (neutral) facial areas before or after treatment. Reference-free current source density (CSD) transformations of ERP waveforms were quantified by temporal principal components analysis (tPCA). Component scores of prominent CSD-tPCA factors sensitive to emotional content were analyzed via permutation tests and repeated measures ANOVA for mixed factorial designs with unstructured covariance matrix, including gender, age and clinical covariates. Factor-based distributed inverse solutions provided descriptive estimates of emotional brain activations at group level corresponding to hierarchical activations along ventral visual processing stream. Risk status affected emotional responsivity (increased positivity to negative-than-neutral stimuli) overlapping early N2 sink (peak latency 212 ms), P3 source (385 ms), and a late centroparietal source (630 ms). High risk individuals had reduced right-greater-thanleft emotional lateralization involving occipitotemporal cortex (N2 sink) and bilaterally reduced emotional effects involving posterior cingulate (P3 source) and inferior temporal cortex (630 ms) when compared to those at low risk. While the early emotional effects were enhanced for left hemifield (right hemisphere) presentations, hemifield modulations did not differ between risk groups, suggesting top-down rather than bottom-up effects of risk. Groups did not differ in their stimulus valence or arousal ratings. Similar effects were seen for individuals with a lifetime history of depression or anxiety disorder in comparison to those without. However, there was no evidence that risk status and history of MDD or anxiety disorder interacted in their impact on emotional responsivity, suggesting largely independent attenuation of attentional resource allocation to enhance perceptual processing of motivationally salient stimuli. These findings further suggest that a deficit in motivated attention preceding conscious awareness may be a marker of risk for depression

Evoked Potentials during Language Processing as Neurophysiological Phenomena

The evoked, event-related potential of the EEG has been extensively employed to study language processing. But what is the ERP? An extensive discussion of contemporary theories about the neurophysiology underlying late ERPs is given. Then, in a series of experiments, domain-general perspectives on ERP components are tested regarding their applicability for language-related brain activity. A range of analysis methods (some of which have not been previously applied to the study of auditory sentence processing) such as single-trial analyses and independent component decomposition, demonstrate the degree to which domain general mechanisms explain the language-related EEG

An Interface of the Taste and Reward Systems in the Brainstem and Its Role in Feeding

We eat what tastes good. We also eat because it is necessary for our health. In fact, some of the most nutritious foods (e.g., vegetables) are often less appetizing, and the tastiest (e.g., fast food, ice cream) may be the least healthy. Despite the former, we may also have a lower limit of what we accept at which point nutrition becomes irrelevant (e.g., “spinach is just too yucky”). Further, we may eat unhealthily because of overwhelming urges. We investigated the complex interactions of taste and feeding at the neurobiological level using the experiments described. In one sense, this neurobiology begins at the periphery with information about ingested substances (i.e., presumably food) being sent to central nuclei. The taste pathways provide one of these routes to the central nervous system. In terms of regulating feeding, we have the neurobiological substrates for urge, pleasure, and displeasure. The relationship of the dopamine (DA) system with reward is well-known, and indeed, studies have shown taste nuclei project to these areas. Since earlier studies and data collected in our lab showed that the neurons of the parabrachial nucleus (PBN) projected to the ventral tegmental area (VTA), and lesioning the PBN attenuates taste-elicited release of DA in the nucleus accumbens, we hypothesized this connection plays a crucial role in the control of feeding, especially with regard to the processing of both appetitive and aversive stimuli, and the relationship of this processing to classical reward circuitry. We therefore utilized a number of neuroanatomical and behavioral techniques to probe taste and intake-related activity in the PBN, VTA, and the PBN-to-VTA circuit. The overarching goal was to contribute to a comprehensive understanding of the taste and reward neural mechanisms that mediate feeding. We used a variety of immunohistochemical methods to test our hypotheses, including one measuring c-Fos-like immunoreactivity (FLI) in neurons (a measure that correlates with neuronal activation in some systems such as taste). Intraoral stimuli increased FLI in the PBN across a number of subnuclei, and in this case, we used a diaminobenzidine stain (DAB) with brightfield microscopy. Comparing C57BL6/J (B6) with mice lacking TRPM5 (KO) showed that some of this increase is driven by taste receptor input, but this effect is predominantly for quinine hydrochloride (QHCl). On the other hand, increases in FLI to sucrose (relative to water) in the lateral PBN were the same for both B6 and KO mice, leading to the conclusion that this FLI may be visceral in nature. Sucrose-elicited FLI in the external lateral subnucleus (el) was probably visceral, whereas QHCl-elicited FLI there was taste-related. We also combined measurement of FLI with retrograde tracing under fluorescent microscopy to compare activity in PBN projections to the VTA and gustatory thalamus (VPMpc). Retrograde tracing revealed two largely independent projections, with VTA-projecting neurons found more contralaterally, and VPMpc-projecting neurons found ipsilaterally. However, both types of cells are found in the caudal, gustatory “waist” portion of the PBN. Interestingly, there is a lack of VTA-projecting cells in the el. Patterns of FLI were consistent with the DAB experiment, except with higher expression as compared to water in this fluorescent experiment in a few subnuclei. This may have been due to methodological differences. As for double-labeled cells, more VTA-projecting cells expressed FLI in response to sucrose or QHCl than to water; this numbered to only about 5% of cells, however, and did not differ according to side. This was compared to double-labeling in VPMpc- projecting cells, where the percent of tracer was around 10% for both QHCl and sucrose on the ipsilateral side and 5% on the contralateral side. We looked at FLI throughout the VTA as well to see if the activity indicated there was a differential response to stimuli with varying taste valence. First, using the same intraorally-stimulated mice with DAB-stained sections, we observed FLI in the VTA. It did not occur in a stimulus-specific fashion and apparently not in a taste-dependent fashion (no significant differences between B6 and KO). In another experiment using fluorescent stains and confocal microscopy, we looked at the FLI in the VTA while delineating it by subnuclei, counting section by section, and identifying DA and GABA cell types. There were many more DA cells in the VTA than GABA cells, and they had distinct patterns of expression across subnuclei and section levels (i.e., within the anteroposterior [AP] dimension). The rostromedial tegmental area was located as a region with higher GABA cell expression. More DA cells were double-labeled with FLI for QHCl than for water or sucrose in the caudal linear nucleus of the raphe. Few GABA cells were double-labeled with FLI. To show the PBN-to-VTA circuit’s role in taste-mediated feeding, we attempted a procedure that would selectively activate VTA-projecting PBN neurons using designer receptors exclusively activated by designer drugs (DREADDs). However, we were unable to verify the efficacy of clozapine-N-oxide to activate the circuit and opted for an alternative manipulation. We instead inhibited the VTA with direct injections of the GABA agonist, muscimol. This resulted in mice reducing their licking (relative to baseline) of sucralose, but not QHCl or water (i.e., an arrangement of non-caloric stimuli with palatable, aversive, and neutral valence). Muscimol also reduced licking of sucrose and QHCl-adulterated sucrose (i.e., caloric stimuli). The reduction in licking to caloric stimuli was accompanied by a decrease in the rate of intake, i.e., muscimol-inhibited mice slowed their lick rate and possibly stopped licking sooner compared to vehicle- injected controls. Overall, this project confirmed that both the PBN and VTA function to communicate taste and reward information. Although the PBN-to-VTA circuit’s function remained elusive, the evidence of the direct path connecting these two nuclei was fortified. Further, to our knowledge, this was the first time evidence was found of its existence as a PBN projection pathway that is mostly separate from the projection to the gustatory thalamus. Combined with the knowledge of this circuit, the activity in these nuclei and the ability to affect consumption by inactivating the VTA suggest the PBN and VTA work together to influence feeding by detecting and integrating information about palatability and calories

The influence of facial attractiveness on recognition memory: behavioural findings and electrophysiological evidence

Die Fähigkeit, Gesichter gut zu erkennen ist entscheidend für unsere sozialen Interaktionen, aber anfällig für Verzerrungen zugunsten bestimmter Gesichtergruppen, bspw. einem besseren Gedächtnis für Gesichter der eigenen Ethnie (Own-Race-Bias). Die Literatur diskutiert potentiell zugrundeliegende Mechanismen kontrovers: Einerseits argumentieren Theorien sozialer Kognition, dass Menschen motivierter seien, Gesichter ihrer eigenen sozialen Gruppe zu individualisieren, was zu effizienterer Verarbeitung und damit besseren Gedächtnisleistung führe. Andererseits gehen Theorien der Wahrnehmungsexpertise davon aus, dass ein besseres Gedächtnis für bestimmte Gesichtergruppen aus Lernprozessen durch regelmäßigen Kontakt mit verschiedenen Gesichtern dieser Kategorie resultiert. Anliegen dieser Arbeit war es, die Vorhersagen dieser Theorien für das Gedächtnis für attraktive, mittelattraktive und unattraktive Gesichter gegeneinander zu testen unter Kontrolle von wahrgenommenen Distinktheit, einer Determinante des Gesichtergedächtnisses. In der ersten Studie wurde untersucht, ob die Erinnerung an Gesichter linear oder auf komplexere Art mit Attraktivität zusammenhängt. Die zweite Studie untersucht den kombinierten Einfluss von Attraktivität und Geschlecht auf das Gesichtergedächtnis. Während sich diese ersten Experimente auf Gedächtniseffekte beim Abruf konzentrierten, untersucht eine dritte Studie enkodierungsrelatierte neuronale Korrelate des Attraktivitätseffekts. Es fand sich wiederholt ein besseres Gedächtnis für unattraktive Gesichter gegenüber attraktiven und mittelattraktiven Gesichtern. Mittelattraktive Gesichter wurden weiterhin schlechter erinnert als attraktive Gesichter. Letzterer Unterschied beruht mutmaßlich auf emotionaler Relevanz, d. h. Valenz und Erregung. In den ereigniskorrelierten Potentialen im EEG zeigten sich erhöhte P2-Amplituden für mittelattraktive Gesichter beim Gedächtnisabruf, und ein ausgeprägter Dm-Effekt in derselben Komponente, die mit Prozessen der perzeptuellen Verarbeitung von Gesichtern in Verbindung gebracht wird. Diese Befunde sprechen übergreifend für Theorien der Wahrnehmungsexpertise, basierend auf der Dichte von Gesichterrepräsentationen

The contributions of sleep-related consolidation to emotional item and associative memory.

Extant empirical evidence of the past two decades suggests a pivotal role of sleep in system consolidation of episodic memory. Models of active system consolidation (Diekelmann & Born, 2010; Rasch & Born, 2013) propose that periods of restricted sensory processing that are pervasive during slow wave sleep (SWS) provide the opportunity of coordinated reactivations. These reactivations are assumed to result in subsequent redistribution of memory representations from intermediate maintenance in the hippocampus toward long-term storage in neocortical networks. However, newly emerging evidence (Genzel, Spoormaker, Konrad, & Dresler, 2015; Hutchison & Rathore, 2015) indicates that a consolidation process, which is highly distinct from the former framework, unfolds across periods of rapid eye movement (REM) sleep, fostering the selective enhancement of emotional memory retrieval. Critically, the interactions of both processes with regard to emotional associative memory have remained largely unexplored at present. This motivated the objectives of the present thesis, which aimed to generate a more comprehensive understanding of the differential contributions of consolidation processes during SWS and REM sleep to (non-)emotional item and associative memory retention. This was addressed in two consecutive experiments, which examined behavioral performance changes across different intervals of sleep, and aimed to link these to specific oscillatory features of SWS (sleep spindle activity) and REM sleep (right-frontal theta lateralization). In experiment 1 consolidation processes were studied in a split-night-design, which contrasts the effects of early night sleep (entailing high amounts of SWS) with those of late night sleep (which is predominated by REM sleep episodes). In order to dissociate item memory from distinct retrieval of contextual features, participants performed a source memory task that ascertained the accurate recognition of (non-)emotional images, as well as the accurate retrieval of the initial screen location (right or left) during encoding. Analyses revealed a significant consolidation benefit for emotional images with regard to item recognition, irrespective of sleep. Source memory performance was differentially modulated across early and late night sleep as a function of stimulus valence. While early night sleep was associated with a selective retention benefit for neutral source memory, late night sleep yielded a selective benefit to emotional source recognition across sleep. This dissociation was further substantiated on a neurophysiological level, by means of selective correlations between spindle power (SWS) and neutral memory performance in the early sleep group, which was complimented by a selective association between right-frontal theta laterality (REM sleep), and emotional source recognition in the late sleep group. As such, the results of experiment 1 genuinely revealed dissociable processes related to the consolidation of emotional and neutral source memory emerging across sleep. Moreover, this extends prior conceptions (Spoormaker, Czisch, & Holsboer, 2013) of consolidation processes during REM sleep, as these were believed to be confined to item memory reprocessing. Experiment 2 attempted to address the generalizability of these previous findings with regard to the critical timing and duration of these consolidation processes, as well as concerning the effects of perceptual integration processes at the encoding stage. In order to examine performance changes across a restricted sleep interval entailing high proportions of REM sleep, an early morning nap paradigm was employed in which participants were randomly allocated to a wakeful control condition or to a 120-minute nap sleep condition in the early morning hours. As previous effects with regard to REM sleep (experiment 1) may be bound to certain preconditions at encoding (Murray & Kensinger, 2012), specifically to the inherent level of perceptual integration between emotional items and source features, experiment 2 adopted a different approach requiring the active integration of both components at the encoding stage. To this end, item and associative recognition were probed by means of a paired-associates task, which required the accurate retrieval of arbitrary object-scene-associations (entailing emotional or neutral scenes) formed during the encoding phase. Analyses yielded a selective, sleep-related retention benefit in associative recognition for both stimulus categories. However, this benefit in performance was again partially dissociable on a neurophysiological level as evident by selective correlations between spindle density during non-rapid eye movement (NREM) sleep and neutral associative memory performance. These results reinforce the former findings of experiment 1, demonstrating that similar consolidation effects related to SWS and REM sleep can be retained on a behavioral level after a brief interval of sleep during the daytime and in a dissimilar task design, requiring active integration of item and context at encoding. However, the lack of a robust correlation with regard to right-frontal theta lateralization signifies that the circadian modulations and neurophysiological specifics of REM sleep, place certain restrictions on the accurate assessment of related processes in diurnal nap paradigms. In summary, the present thesis constitutes a first systematic approach towards dissociating the contributions of REM sleep and SWS to emotional associative memory consolidation, across two consecutive but dissimilar study designs. The yielded findings originally suggest that consolidation processes during both sleep stages are dissociable, but beyond this, contribute independently to memory retention of emotional and neutral associations. This was also substantiated on a neurophysiological level with regard to selective correlations between oscillatory features of both sleep stages and memory performance. Moreover, in support of previous conceptions (Hutchison & Rathore, 2015), it was genuinely established that REM sleep exhibits the unique capacity to influence associative memory of emotional stimuli. The exact mechanism by which this is accomplished remains to be elucidated in future experiments.Eine Vielzahl empirischer Befunde der letzten zwei Jahrzehnte belegen, dass der Schlaf eine tiefgreifende Rolle in der Gedächtniskonsolidierung zwischen unterschiedlichen Gedächtnissystems einnimmt. Sukzessive verfeinerte Modelle über aktive Vorgänge der „Systemkonsolidierung“ (Diekelmann & Born, 2010; Rasch & Born, 2013) legen nahe, dass Phasen eingeschränkter sensorischer Verarbeitung, die über den Tiefschlaf hinweg dominieren, ein Zeitfenster bieten in dem Gedächtnisspuren im Hippocampus in koordinierter Weise reaktiviert werden können. Diese Reaktivierungen gehen mit einer Integration der jeweiligen Gedächtnisinhalte in neokortikalen Netzwerken einher, die eine langfristige Aufrechterhaltung des Gedächtnisabrufs ermöglichen. Neue Befunde (Genzel et al., 2015; Hutchison & Rathore, 2015) legen allerdings nahe, dass sich ein weiterer Konsolidierungsprozess über den Schlaf hinweg vollzieht, der zu einer selektiven Aufrechterhaltung emotionaler Gedächtnisinhalte beiträgt. Dieser Prozess ist wiederum assoziiert mit dem Auftreten von REM-Schlaf (REM, engl. Rapid Eye Movement) Episoden. Bislang ist jedoch unklar, wie beide Konsolidierungsprozesse über unterschiedliche Schlafstadien hinweg miteinander interagieren in Bezug auf das emotionale Assoziationsgedächtnis. Dies bildete den Ausgangspunkt der vorliegenden Arbeit, die ein umfassenderes Verständnis hinsichtlich der Beiträge unterschiedlicher Konsolidierungsprozesse im Tiefschlaf und REM Schlaf in der Aufrechterhaltung des (nicht-)emotionalen Item- und Assoziationsgedächtnisses anstrebt. Dies wurde in zwei aufeinander aufbauenden Experimenten näher beleuchtet, in denen behaviorale Leistungsveränderungen über unterschiedliche Schlafintervalle untersucht wurden mit dem Ziel diese mit spezifischen oszillatorischen Merkmalen des Tiefschlafs (Schlafspindel Aktivität) und des REM Schlafs (Rechts-frontale Theta Lateralisierung) in Verbindung zu bringen. In Experiment 1 wurden diese Konsolidierungsprozesse in einem „Split-night-design“ untersucht, das die Möglichkeit bietet, frühen Nachtschlaf (mit hoher Tiefschlafdauer) mit spätem Nachtschlaf (der von REM-Schlaf Episoden dominiert wird) zu kontrastieren. Um das Itemgedächtnis von dem distinkten Abruf kontextueller Merkmale dissoziieren zu können, wurde eine Quellengedächtnisaufgabe von den Probanden bearbeitet, in der sowohl das Wiedererkennen (nicht)emotionaler Bilder als auch der Abruf der initialen Bildschirmposition (rechts oder links) in der Lernphase erfasst wurde. Die berichteten Analysen weisen auf einen signifikanten Konsolidierungsvorteil für das Wiedererkennen emotionaler Bilder über die Zeit hinweg hin, der jedoch unabhängig vom Schlaf auftritt. Die Quellengedächtnisleistung wird hingegen differentiell über den frühen und späten Nachtschlaf in Abhängigkeit von der Stimulusvalenz aufrechterhalten. Während früher Nachtschlaf mit einer selektiven Aufrechterhaltung des neutralen Quellengedächtnisses assoziiert war, konnte der späte Nachtschlaf mit einer selektiven Erhaltung des emotionalen Quellengedächtnisses in Verbindung gebracht werden. Diese Dissoziation war darüber hinaus auf neurophysiologischer Ebene nachweisbar anhand selektiver Korrelationen zwischen der Spindelaktivität im Tiefschlaf und der neutralen Gedächtnisleistung über den frühen Nachtschlaf und einer selektiven Korrelation zwischen der rechts-frontalen Theta Lateralisierung im REM Schlaf und der emotionalen Quellengedächtnisleistung über den späten Nachtschlaf. Die Ergebnisse des ersten Experiments eröffnen eine neue Perspektive, indem sie die Existenz zweier dissoziierbarer Prozesse in der Konsolidierung des emotionalen und neutralen Quellengedächtnisses über den Schlaf hinweg nahelegen. Im Zuge dessen erweitern die vorliegenden Ergebnisse vorangegangene Konzepte (Spoormaker et al., 2013) der Gedächtniskonsolidierung im REM Schlaf, die bislang eine eingeschränkte Wirkung auf das Itemgedächtnis prädizierten. Das Ziel von Experiment 2 war es, diese neuen Ergebnisse auf ihre Generalisierbarkeit hin zu prüfen, insbesondere hinsichtlich der kritischen Zeitverlaufs und der Dauer der zugrundliegenden Konsolidierungsprozesse und in Bezug auf die Bedeutung perzeptueller Integrationsprozesse während der Enkodierphase. Um Veränderungen in der Gedächtnisleistung über ein kurzes Schlafintervall mit hohen REM-Schlaf-Anteilen zu untersuchen wurde ein Kurzschlaf Paradigma am frühen Morgen eingesetzt in dem Probanden einer Wachkontrollbedingung oder einer 120-minütigen Tagschlafbedingung am frühen Morgen zugewiesen wurden. Die vorangegangenen Ergebnisse aus Experiment 1 hinsichtlich der Effekte des REM-Schlafs könnten unter Zugrundelegung der Literatur (Murray & Kensinger, 2013) an bestimmte Bedingungen während er Enkodierungsphase gekoppelt sein, speziell an den inhärente Grad der perzeptuellen Integration zwischen emotionalen Items und ihren Quellenmerkmalen. Um dies zu prüfen wurde in Experiment 2 eine andere Herangehensweise mit einer Gedächtnisaufgabe, die eine aktive Integration beider Komponenten während der Enkodierung erforderlich machte, gewählt. Item- und Assoziationsgedächtnis wurden über das Behalten paarweise gelernter Assoziationen zwischen (nicht)emotionalen Bildern und Alltagsobjekten erfasst. Die korrespondierenden Analysen erbrachten einen selektiven, schlafbezogenen Vorteil in der Aufrechterhaltung der assoziativen Gedächtnisleistung über die Zeit hinweg in beiden Stimuluskategorien. Darüber hinaus war dieser Effekt erneut teilweise dissoziierbar auf neurophysiologischer Ebene, was sich in selektiven Korrelationen der Spindeldichte während des non-rapid eye movement (NREM) Schlafs zu der neutralen Assoziationsgedächtnisleistung wiederspiegelte. Diese Ergebnisse untermauern die vorangegangen Befunde aus Experiment 2, indem ähnliche Konsolidierungseffekte des Tiefschlafs und des REM Schlafs über ein kurzes Schlafintervall am frühen Morgen und innerhalb eines Aufgaben-Paradigmas, dass die aktive Integration während der Enkodierungsphase erforderte, auf behavioraler Ebene bestätigt werden konnten. Dennoch verweist das Ausbleiben einer robusten Korrelation zu der rechts-frontalen Theta Lateralisierung im REM-Schlaf darauf, dass zirkadiane Modulationen und neurophysiologische Besonderheiten des REM-Schlafs gewisse Begrenzungen in der akkuraten Erfassung dieser Prozesse innerhalb von Kurzschlaf-Paradigmen während des Tages setzen. Die vorliegende Arbeit stellt eine erste systematische Annäherung an eine Dissoziierung der Beiträge des Tiefschlafs und des REM-Schlafs in der Konsolidierung des emotionalen Assoziationsgedächtnisses dar, die über zwei aufeinander aufbauende aber unterschiedliche Studiendesigns hinweg angestrebt wurde. Die daraus hervorgegangenen Ergebnisse legen erstmals nahe, dass Konsolidierungsprozesse über beide Schlafstadien dissoziierbar sind aber darüber hinaus gehend eigenständig zu einer Aufrechterhaltung der Gedächtnisleistung für neutrale und emotionale Assoziationen beitragen. Dies konnte auch auf neurophysiologischer Ebene über selektive Korrelationen zu oszillatorischen Merkmalen beider Schlafstadien substantiiert werden. Darüber hinaus konnte erstmalig nachgewiesen werden, dass Prozesse während des REM Schlaf über die Kapazität verfügen auf das assoziative Erinnern emotionaler Inhalte einzuwirken in Übereinstimmung zu neueren theoretischen Konzepten (Hutchison & Rathore, 2015). Der genaue Mechanismus über den dies bewirkt wird muss in zukünftigen Experimenten näher beleuchtet werden

Electrophysiological Signatures of Fear Conditioning: From Methodological Considerations to Catecholaminergic Mechanisms and Translational Perspectives

Fear conditioning describes a learning mechanism during which a specific stimulus gets associated with an aversive event (i.e., an unconditioned stimulus; US). Thereby, this initially neutral or arbitrary stimulus becomes a so-called “conditioned” stimulus (CS), which elicits a conditioned threat response. Fear extinction refers to the decrease in conditioned threat responses as soon as the CS is repeatedly presented in the absence of the US. While fear conditioning is an important learning model for understanding the etiology and maintenance of anxiety and fear-related disorders, extinction learning is considered to reflect the most important learning process of exposure therapy. Neurophysiological signatures of fear conditioning have been widely studied in rodents, leading to the development of groundbreaking neurobiological models, including brain regions such as the amygdala, insula, and prefrontal areas. These models aim to explain neural mechanisms of threat processing, with the ultimate goal to improve treatment strategies for pathological fear. Recording intracranial electrical activity of single units in animals offers the opportunity to uncover neural processes involved in threat processing with excellent spatial and temporal resolution. A large body of functional magnetic resonance imaging (fMRI) studies have helped to translate this knowledge about the anatomy of fear conditioning into the human realm. fMRI is an imaging technique with a high spatial resolution that is well suited to study slower brain processes. However, the temporal resolution of fMRI is relatively poor. By contrast, electroencephalography (EEG) is a neuroscientific method to capture fast and transient cortical processes. While EEG offers promising opportunities to unravel the speed of neural threat processing, it also provides the possibility to study oscillatory brain activity (e.g., prefrontal theta oscillations). The present thesis contains six research manuscripts, describing fear conditioning studies that mainly applied EEG methods in combination with other central (fMRI) and peripheral (skin conductance, heart rate, and fear-potentiated startle) measures. A special focus of this thesis lies in methodological considerations for EEG fear conditioning research. In addition, catecholaminergic mechanisms are studied, with the ultimate goal of opening up new translational perspectives. Taken together, the present thesis addresses several methodological challenges for neuroscientific (in particular, EEG) fear conditioning research (e.g., appropriate US types and experimental designs, signal-to-noise ratio, simultaneous EEG-fMRI). Furthermore, this thesis gives critical insight into catecholaminergic (noradrenaline and dopamine) mechanisms. A variety of neuroscientific methods (e.g., EEG, fMRI, peripheral physiology, pharmacological manipulation, genetic associations) have been combined, an approach that allowed us (a) to translate knowledge from animal studies to human research, and (b) to stimulate novel clinical directions