When Is Simultaneous Recording Necessary? A Guide for Researchers Considering Combined EEG-fMRI.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provide non-invasive measures of brain activity at varying spatial and temporal scales, offering different views on brain function for both clinical and experimental applications. Simultaneous recording of these measures attempts to maximize the respective strengths of each method, while compensating for their weaknesses. However, combined recording is not necessary to address all research questions of interest, and experiments may have greater statistical power to detect effects by maximizing the signal-to-noise ratio in separate recording sessions. While several existing papers discuss the reasons for or against combined recording, this article aims to synthesize these arguments into a flow chart of questions that researchers can consider when deciding whether to record EEG and fMRI separately or simultaneously. Given the potential advantages of simultaneous EEG-fMRI, the aim is to provide an initial overview of the most important concepts and to direct readers to relevant literature that will aid them in this decision

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

Simultaneous EEG-fMRI : novel methods for EEG artefacts reduction at source

This thesis describes the development and application of novel techniques to reduce the EEG artefacts at source during the simultaneous acquisition of EEG and fMRI data. The work described in this thesis was carried out by the author in the Sir Peter Mansfield Magnetic Resonance Centre, School of Physics & Astronomy at the University of Nottingham, between October 2010 and January 2013. Large artefacts compromise EEG data quality during simultaneous fMRI. These artefact voltages pose heavy demands on the bandwidth and dynamic range of EEG amplifiers and mean that even small fractional variations in the artefact voltages give rise to significant residual artefacts after correction, which can easily swamp signals from brain activity. Therefore any intrinsic reduction in the magnitude of the artefacts would be highly advantageous, allowing data with a higher bandwidth to be acquired without amplifier saturation, and facilitating improved detection of brain activity. This thesis firstly explores a new method for reducing the gradient artefact (GA), which is induced in EEG data recorded during concurrent MRI, by investigating the effects of the cable configuration on the characteristics of the GA. This work showed that the GA amplitude and its sensitivity to movement of the cabling is reduced by minimising wire loop areas in the cabling between the EEG cap and amplifier. Another novel approach for reducing the magnitude and variability of the artefacts is the use of an EEG cap that incorporates electrodes embedded in a reference layer, which has a similar conductivity to tissue and is electrically isolated from the scalp. With this arrangement, the artefact voltages produced on the reference layer leads are theoretically similar to those induced in the scalp leads, but neuronal signals are not detected in the reference layer. Therefore taking the difference of the voltages in the reference and scalp channels should reduce the artefacts, without affecting sensitivity to neuronal signals. The theoretical efficacy of artefact correction that can be achieved by using this new reference layer artefact subtraction (RLAS) method was investigated. This was done through separate electromagnetic simulations of the artefacts induced in a hemispherical reference layer and a spherical volume conductor in a time-varying magnetic field and the results showed that similar artefacts are induced on the surface of both conductors. Simulations are also performed to find the optimal design for an RLAS system, by varying the geometry of the system. A simple experimental realisation of the RLAS system was implemented to investigate the degree of artefact attenuation that can be achieved via RLAS. Through a series of experiments on phantoms and human subjects, it is shown here that RLAS significantly reduces the GA, pulse (PA) and motion (MA) artefacts, while allowing accurate recording of neuronal signals. The results indicate that RLAS generally outperforms the standard artefact correction method, average artefact subtraction (AAS), in the removal of the GA and PA when motion is present, while the combination of RLAS and AAS always produces higher artefact attenuation than AAS alone. Additionally, this work demonstrates that RLAS greatly attenuates the unpredictable and highly variable MA that are very hard to remove using post-processing methods

Simultaneous EEG-fMRI : novel methods for EEG artefacts reduction at source

This thesis describes the development and application of novel techniques to reduce the EEG artefacts at source during the simultaneous acquisition of EEG and fMRI data. The work described in this thesis was carried out by the author in the Sir Peter Mansfield Magnetic Resonance Centre, School of Physics & Astronomy at the University of Nottingham, between October 2010 and January 2013. Large artefacts compromise EEG data quality during simultaneous fMRI. These artefact voltages pose heavy demands on the bandwidth and dynamic range of EEG amplifiers and mean that even small fractional variations in the artefact voltages give rise to significant residual artefacts after correction, which can easily swamp signals from brain activity. Therefore any intrinsic reduction in the magnitude of the artefacts would be highly advantageous, allowing data with a higher bandwidth to be acquired without amplifier saturation, and facilitating improved detection of brain activity. This thesis firstly explores a new method for reducing the gradient artefact (GA), which is induced in EEG data recorded during concurrent MRI, by investigating the effects of the cable configuration on the characteristics of the GA. This work showed that the GA amplitude and its sensitivity to movement of the cabling is reduced by minimising wire loop areas in the cabling between the EEG cap and amplifier. Another novel approach for reducing the magnitude and variability of the artefacts is the use of an EEG cap that incorporates electrodes embedded in a reference layer, which has a similar conductivity to tissue and is electrically isolated from the scalp. With this arrangement, the artefact voltages produced on the reference layer leads are theoretically similar to those induced in the scalp leads, but neuronal signals are not detected in the reference layer. Therefore taking the difference of the voltages in the reference and scalp channels should reduce the artefacts, without affecting sensitivity to neuronal signals. The theoretical efficacy of artefact correction that can be achieved by using this new reference layer artefact subtraction (RLAS) method was investigated. This was done through separate electromagnetic simulations of the artefacts induced in a hemispherical reference layer and a spherical volume conductor in a time-varying magnetic field and the results showed that similar artefacts are induced on the surface of both conductors. Simulations are also performed to find the optimal design for an RLAS system, by varying the geometry of the system. A simple experimental realisation of the RLAS system was implemented to investigate the degree of artefact attenuation that can be achieved via RLAS. Through a series of experiments on phantoms and human subjects, it is shown here that RLAS significantly reduces the GA, pulse (PA) and motion (MA) artefacts, while allowing accurate recording of neuronal signals. The results indicate that RLAS generally outperforms the standard artefact correction method, average artefact subtraction (AAS), in the removal of the GA and PA when motion is present, while the combination of RLAS and AAS always produces higher artefact attenuation than AAS alone. Additionally, this work demonstrates that RLAS greatly attenuates the unpredictable and highly variable MA that are very hard to remove using post-processing methods