Disentangling neuronal pre- and post-response activation in the acquisition of goal-directed behavior through the means of co-registered EEG-fMRI

Behavior is considered goal-directed when the actor integrates information about the subsequent outcome of an action (Balleine & O'Doherty, 2010; Dickinson & Balleine, 1994; Kiesel & Koch, 2012), potentially enabling the anticipation of consequences of an action. Thus, it requires prior acquisition of knowledge about the current contingencies between behavioral responses and their outcomes under certain stimulus conditions (J. Hoffmann & Engelkamp, 2013). This association chain enables events lying in the future to be mentally represented and assessed in terms of value and achievability. However, while neural correlates of instructed goal-directed action integration processes have already been examined in a functional magnetic resonance imaging (fMRI) study using this paradigm (Ruge & Wolfensteller, 2015), there has been no information if those processes are also reflected in Electroencephalography (EEG) and if so which specific EEG parameters are modulated by them. This dissertation set out to investigate neurocognitive mechanisms of instructed outcome response learning utilizing two different imaging methods, namely EEG and fMRI. Study 1 was an exploratory study to answer the question what kinds of learning-related EEG correlates were to expect. The O-R outcome integration specific EEG correlates identified in Study 1 served as regressors in a unified general linear model (EEG-informed fMRI analysis) in the co-registered EEG-fMRI study (Study 2). One of the key questions in this study was if the EEG signal could help to differentiate between BOLD pre-response activation associated with processes related to response preparation or initiation and activation associated with post-response outcome integration processes. The foundation to both studies of this work was an experimental paradigm of instructed S-R-O learning, which included a learning and a test phase. Stimuli were four abstract visual patterns that differed in each block. Each visual stimulus required a distinct manual response and was predictably followed by a distinct auditory outcome. Instructions were delivered via a “guided implementation” procedure in which the instruction was embedded within the first three successful behavioral implementation trials. In these first three trials, the visual stimulus was followed by an imperative stimulus highlighting the correct response. The guided implementation phase was followed by an unguided implementation phase where the correct response now had to be retrieved from memory. Behaviorally, the strength of acquired O-R associations can be analyzed via O-R compatibility effects measured in a subsequent outcome-priming test phase (Greenwald, 1970). In this test phase a previously learned outcome becomes an imperative stimulus that requires either the response, which produced that outcome in the preceding learning phase (O-R compatible), or a response, which produced a different outcome (O-R incompatible). The experimental design was embedded into an EEG recording setup in study 1 while study 2 comprised a simultaneous EEG-fMRI recording setup in which EEG scalp potentials were continuously recorded during the experimental session inside the MR scanner bore. Study 1 revealed various ERP markers correlated with outcome response learning. An ERP post-response anterior negativity following auditory outcomes was increasingly attenuated as a function of the acquired association strength. This suggests that previously reported action-induced sensory attenuation effects under extensively trained free choice conditions can be established within few repetitions of specific R-O pairings under forced choice conditions. Furthermore, an even more rapid development of a post-response but pre-outcome fronto-central positivity, which was reduced for high R-O learners, might indicate the rapid deployment of preparatory attention towards predictable outcomes. Finally, the study identified a learning-related stimulus-locked activity modulation within the visual P1-N1 latency range, which was thought to reflect the multi-sensory integration of the perceived antecedent visual stimulus with the anticipated auditory outcome. In general, study 2 was only partially able to replicate the EEG activity dynamics related to the formation of bidirectional R-O associations that were observed in study 1. Primarily, it was able to confirm the modulation in EEG negativity in the visual P1-N1 latency range over the learning course. The EEG-informed analysis revealed that learning-related modulations of the P1-N1 complex are functionally coupled to activation in the orbitofrontal cortex (OFC). More specifically, growing attenuation of the EEG negativity increase from early to late SRO repetition levels in high R-O learners was associated with an increase in activation in the OFC. An additional exploratory EEG analysis identified a recurring post outcome effect at central electrode sites expressed in a stronger negativity in late compared to early learning stages. This effect was present in both studies and showed no correlation with any of the behavioral markers of learning. The EEG-informed fMRI analysis resulted in a pattern of distinct functional couplings of this parameter with different brain regions, each correlated with different behavioral markers of S-R-O learning. First of all, increased coupling between the late EEG negativity and activation in the supplementary motor area (SMA) was positively correlated with the O-R compatibility effect. Thus, high R-O learners exhibited a stronger coupling than low R-O learners. Secondly, increased couplings between the late EEG negativity and activation in the somatosensory cortex as well as the dorsal caudate, on the other hand, were positively correlated with individual reaction time differences between early and late stages of learning. Regarding activation patterns prior to the behavioral response the results indicate that the OFC could serve as a (multimodal) hub for integrating stimulus information and information about its associated outcome in an early pre-stage of action selection and initiation. Learnt S-O contingencies would facilitate initiating the motor program of the action of choice. Hence, the earlier an outcome is anticipated (based on stimulus outcome associations), the better it will be associated with its response, eventually leading to stronger O-R compatibility effects later on. Thus, one could speculate that increased activation in response to S-R-O mappings possibly embodies a marker for the ongoing transition from mere stimulus-based behavior to a goal-directed behavior throughout the learning course. Post-response brain activation revealed a seemingly two-fold feedback integration stream of O-R contingencies. On one hand the SMA seems to be engaged in bidirectional encoding processes of O-R associations. The results promote the general idea that the SMA is involved in the acquisition of goal-directed behavior (Elsner et al., 2002; Melcher, Weidema, Eenshuistra, Hommel, & Gruber, 2008; Melcher et al., 2013). Together with prior research (Frimmel, Wolfensteller, Mohr, & Ruge, 2016) this notion can be generalized not only to extensive learning phases but also to learning tasks in which goal-directed behavior is acquired in only few practice trials. However, there is an ongoing debate on whether SMA activation can be clearly linked to sub-processes prior or subsequent to an agent’s action (Nachev, Kennard, & Husain, 2008). The results of this work provide additional evidence favoring an involvement of the SMA only following a performed action in response to an imperative stimulus and even more, subsequent to the perception of its ensuing effect. This may give rise to the interpretation that the SMA is associated with linking the motor program of the performed action to the sensory program of the perceived effect, hence establishing and strengthening O-R contingencies. Furthermore, the analysis identified an increased coupling of a late negativity in the EEG signal and activation in the dorsal parts of the caudate as well as the somatosensory cortex. The dorsal caudate has not particularly been brought into connection with O-R learning so far. I speculate that the coupling effect in this part of the caudate reflects an ongoing process of an early automatization of the acquired behavior. It has already be shown in a similar paradigm that behavior can be automatized within only few repetitions of novel instructed S-R mappings (Mohr et al., 2016).:Table of contents Table of contents II List of Figures IV List of Tables VI List of Abbreviations VII 1 Summary 1 1.1 Introduction 1 1.2 Study Objectives 2 1.3 Methods 3 1.4 Results 4 1.5 Discussion 4 2 Theoretical Background 7 2.1 Introduction 7 2.2 Theories of acquiring goal-directed behavior 9 2.2.1 Instrumental learning 9 2.2.1.1 Behavioral aspects 9 2.2.1.2 Neurophysiological correlates 14 2.2.2 Acquisition of goal-directed behavior according to ideomotor theory 16 2.2.2.1 Behavioral aspects 16 2.2.2.2 Neurophysiological correlates 22 2.3 Summary 25 2.4 Methodological background 26 2.4.1 Electroencephalography (EEG) 26 2.4.2 Functional magnetic resonance imaging (fMRI) 28 2.4.3 Co-registered EEG-fMRI 29 3 General objectives and research questions 34 4 Study 1 – Learning-related brain-electrical activity dynamics associated with the subsequent impact of learnt action-outcome associations 36 4.1 Introduction 36 4.2 Methods 39 4.3 Results 47 4.4 Discussion 60 5 Study 2 - Within trial distinction of O-R learning-related BOLD activity with the means of co-registered EEG information 64 5.1 Introduction 64 5.2 Methods 66 5.3 Results 86 5.4 Discussion 101 6 Concluding general discussion 109 6.1 Brief assessment of study objectives 109 6.2 Novel insights into rapid instruction based S-R-O learning? 109 6.2.1 Early stimulus outcome information retrieval indicates the transition from stimulus based behavior to goal-directed action 110 6.2.2 Post-response encoding and consolidation of O-R contingencies enables goal-directedness of behavior 112 6.3 Critical reflection of the methodology and outlook 116 6.3.1 Strengths and limitations of this work 116 6.3.2 Data quality assessment 117 6.3.3 A common neural foundation for EEG and fMRI? 119 6.3.4 How can co-registered EEG-fMRI contribute to a better understanding of the human brain? 121 6.4 General Conclusion 123 7 References 124 Danksagung Erklärun

Particle acceleration in cooling flow clusters of galaxies: the case of Abell 2626

It has recently been proposed a theoretical model which accounts for the origin of radio mini-halos observed in some cooling flow clusters as related to electron re-acceleration by MHD turbulence (Gitti, Brunetti & Setti 2002). The MHD turbulence is assumed to be frozen into the flow of the thermal ICM and thus amplified in the cooling flow region. Here we present the application of this model to a new mini-halo candidate, the cluster A2626, and compare the results with those obtained for the mini-halo in the Perseus cluster. We present VLA data at 330 MHz and 1.5 GHz of the diffuse radio emission observed in A2626, and we show that its main properties can be explained by the model. We find that the power necessary for the re-acceleration of the relic electron population is only a factor ~ 0.7% of the maximum power that can be extracted by the cooling flow (as estimated on the basis of the standard model). We also discuss the observational properties of known mini-halos in connection with those of host clusters, showing that the radio power of mini--halos increases with the maximum power of cooling flows. This trend is expected in the framework of the model. Possible effects of new Chandra and XMM-Newton estimates of $\dot{M}$ on this trend are considered: we conclude that even if earlier derived cooling rates were overestimated, cooling flow powers are still well above the radio powers emitted by mini-halos.Comment: 12 pages, 11 figures, accepted for publication in Astronomy & Astrophysic

Cooling by Heat Conduction Inside Magnetic Flux Loops and the Moderate Cluster Cooling Flow Model

I study non-radiative cooling of X-ray emitting gas via heat conduction along magnetic field lines inside magnetic flux loops in cooling flow clusters of galaxies. I find that such heat conduction can reduce the fraction of energy radiated in the X-ray band by a factor of 1.5-2. This non-radiative cooling joins two other proposed non-radiative cooling processes, which can be more efficient. These are mixing of cold and hot gas, and heat conduction initiated by magnetic fields reconnection between hot and cold gas. These processes when incorporated into the moderate cooling flow model lead to a general cooling flow model with the following ingredients. (1) Cooling flow does occur, but with a mass cooling rate about 10 times lower than in old versions of the cooling flow model. Namely, heating occurs such that the effective age of the cooling flow is much below the cluster age, but the heating can't prevent cooling altogether. (2) The cooling flow region is in a non-steady state evolution. (3) Non-radiative cooling of X-ray emitting gas can bring the model to a much better agreement with observations. (4) The general behavior of the cooling flow gas, and in particular the role played by magnetic fields, make the intracluster medium in cooling flow clusters similar in some aspects to the active solar corona.Comment: Submitted to MNRA

Data integration and analysis for circadian medicine

Data integration, data sharing, and standardized analyses are important enablers for data-driven medical research. Circadian medicine is an emerging field with a particularly high need for coordinated and systematic collaboration between researchers from different disciplines. Datasets in circadian medicine are multimodal, ranging from molecular circadian profiles and clinical parameters to physiological measurements and data obtained from (wearable) sensors or reported by patients. Uniquely, data spanning both the time dimension and the spatial dimension (across tissues) are needed to obtain a holistic view of the circadian system. The study of human rhythms in the context of circadian medicine has to confront the heterogeneity of clock properties within and across subjects and our inability to repeatedly obtain relevant biosamples from one subject. This requires informatics solutions for integrating and visualizing relevant data types at various temporal resolutions ranging from milliseconds and seconds to minutes and several hours. Associated challenges range from a lack of standards that can be used to represent all required data in a common interoperable form, to challenges related to data storage, to the need to perform transformations for integrated visualizations, and to privacy issues. The downstream analysis of circadian rhythms requires specialized approaches for the identification, characterization, and discrimination of rhythms. We conclude that circadian medicine research provides an ideal environment for developing innovative methods to address challenges related to the collection, integration, visualization, and analysis of multimodal multidimensional biomedical data.Peer Reviewe

The parsec-scale properties of the radio galaxy 4C 26.42 in the dense cooling core cluster A1795

The aim of the present work is to study the radio emission on the parsec scale of 4C 26.42, the Brightest cluster galaxy in Abell 1795, in the framework of radiosources in a dense cool core cluster. We present Very Long Baseline Array (VLBA) observations at 1.6, 5, 8.4 and 22 GHz. We performed a spectral index and multiepoch analysis. The source appears two-sided with a well defined and symmetric Z-structure at ~5 mas from the core. The kiloparsec-scale morphology is similar to the parsec-scale structure, but reversed in P.A., with symmetric 90 deg. bends at about 2 arcsec from the nuclear region. Comparing data obtained at 3 different epochs we derive a 3$\sigma$ limit to the apparent proper motion of $\beta_a$ < 0.04. We suggest that the parsec-scale jets are sub-relativistic, in contrast with the high velocities found for most low-power radio galaxies. The origin of the unusual radio morphology remains a puzzle. We suggest that the identification of the parent galaxy with the central cD in a cooling cluster plays an important role in the properties and structure of the jets.Comment: 8 pages, 4 figures, 4 tables, Accepted for pubblication in Astronomy & Astrophysic

Two Clusters with Radio-quiet Cooling Cores

Radio lobes inflated by active galactic nuclei at the centers of clusters are a promising candidate for halting condensation in clusters with short central cooling times because they are common in such clusters. In order to test the AGN-heating hypothesis, we obtained Chandra observations of two clusters with short central cooling times yet no evidence for AGN activity: Abell 1650 and Abell 2244. The cores of these clusters indeed appear systematically different from cores with more prominent radio emission. They do not have significant central temperature gradients, and their central entropy levels are markedly higher than in clusters with stronger radio emission, corresponding to central cooling times ~ 1 Gigayear. Also, there is no evidence for fossil X-ray cavities produced by an earlier episode of AGN heating. We suggest that either (1) the central gas has not yet cooled to the point at which feedback is necessary to prevent it from condensing, possibly because it is conductively stabilized, or (2) the gas experienced a major heating event $\gtrsim 1$ Gyr in the past and has not required feedback since then. The fact that these clusters with no evident feedback have higher central entropy and therefore longer central cooling times than clusters with obvious AGN feedback strongly suggests that AGNs supply the feedback necessary to suppress condensation in clusters with short central cooling times.Comment: ApJ Letter, in pres

Cold filaments in galaxy clusters: effects of heat conduction

We determine the critical size l_crit of a filament of cold (T~10^4 K) gas that is in radiative equilibrium with X-ray emitting gas at temperatures T_out~10^6 - 10^8 K. Filaments smaller than l_crit will be rapidly evaporated, while longer ones will induce the condensation of the ambient medium. At fixed pressure P, l_crit increases as T_out^(11/4), while at fixed T_out it scales as 1/P. It scales as f^(1/2), where f is the factor by which the magnetic field depresses the thermal conductivity below Spitzer's benchmark value. For plausible values of f, l_crit is similar to the lengths of observed filaments. In a cluster such as Perseus, the value of l_crit increases by over an order of magnitude between the centre and a radius of 100 kpc. If the spectrum of seed filament lengths l is strongly falling with l, as is natural, then these results explain why filaments are only seen within a few kiloparsecs of the centres of clusters, and are not seen in clusters that have no cooling flow. We calculate the differential emission measure as a function of temperature for the interface between filaments and ambient gas of various temperatures. We discuss the implications of our results for the origin of the galaxy luminosity function.Comment: 8 pages with 5 figures, MNRAS (submitted

Radio Jets in Galaxies with Actively Accreting Black Holes: new insights from the SDSS

The majority of nearby radio-loud AGN are found in massive, old elliptical galaxies with weak emission lines. At high redshifts,however, most known radio AGN have strong emission lines. In this paper, we examine a subset of radio AGN with emission lines selected from the Sloan Digital Sky Survey. The probability for a nearby radio AGN to have emission lines is a strongly decreasing function of galaxy mass and an increasing function of radio luminosity above 10^25 W/Hz. Emission line and radio luminosities are correlated, but with large dispersion. At a given radio power, AGN with small black holes have higher [OIII] luminosities (which we interpret as higher accretion rates) than AGN with big black holes. However, if we scale both radio and emission line luminosities by the black hole mass, we find a correlation between normalized radio power and accretion rate in Eddington units that is independent of black hole mass. There is also a clear correlation between normalized radio power and the age of the stellar population in the galaxy. Present-day AGN with the highest normalized radio powers are confined to galaxies with small black holes. High-redshift, high radio-luminosity AGN could be explained if big black holes were similarly active at earlier cosmic epochs. To investigate why only a small fraction of emission line AGN become radio loud, we create matched samples of radio-loud and radio-quiet AGN and compare their host galaxy properties and environments. The main difference lies in their environments; our local density estimates are a factor 2 larger around the radio-loud AGN. We propose a scenario in which radio-loud AGN with emission lines are located in galaxies where accretion of both cold and hot gas can occur simultaneously. (Abridged)Comment: 18 figures, submitted to MNRA