Adaptive Thresholding for Improving Sensitivity in Single-Trial Simultaneous EEG/fMRI

A common approach used to fuse simultaneously recorded EEG and fMRI is to correlate trial-by-trial variability in the EEG, or variability of components derived therefrom, with the blood oxygenation level dependent response. When this correlation is done using the conventional univariate approach, for example with the general linear model, there is the usual problem of correcting the statistics for multiple comparisons. Cluster thresholding is often used as the correction of choice, though in many cases it is utilized in an ad hoc way, for example by employing the same cluster thresholds for both traditional regressors (stimulus or behaviorally derived) and EEG-derived regressors. In this paper we describe a resampling procedure that takes into account the a priori statistics of the trial-to-trial variability of the EEG-derived regressors in a way that trades off cluster size and maximum voxel Z-score to properly correct for multiple comparisons. We show that this data adaptive procedure improves sensitivity for smaller clusters of activation, without sacrificing the specificity of the results. Our results suggest that extra care is needed in correcting statistics when the regressor model is derived from noisy and/or uncertain measurements, as is the case for regressors constructed from single-trial variations in the EEG

Exploring the relative efficacy of motion artefact correction techniques for EEG data acquired during simultaneous fMRI

Simultaneous EEG-fMRI allows multi-parametric characterisation of brain function, in principle enabling a more complete understanding of brain responses; unfortunately the hostile MRI environment severely reduces EEG data quality. Simply eliminating data segments containing gross motion artefacts [MAs] (generated by movement of the EEG system and head in the MRI scanner’s static magnetic field) was previously believed sufficient. However recently the importance of removal of all MAs has been highlighted and new methods developed.A systematic comparison of the ability to remove MAs and retain underlying neuronal activity using different methods of MA detection and post-processing algorithms is needed to guide the neuroscience community. Using a head phantom, we recorded MAs while simultaneously monitoring the motion using three different approaches: Reference Layer Artefact Subtraction (RLAS), Moire Phase Tracker (MPT) markers, and Wire Loop Motion Sensors (WLMS). These EEG recordings were combined with EEG responses to simple visual tasks acquired on a subject outside the MRI environment. MAs were then corrected using the motion information collected with each of the methods combined with different analysis pipelines.All tested methods retained the neuronal signal. However, often the MA was not removed sufficiently to allow accurate detection of the underlying neuronal signal. We show that the MA is best corrected using the RLAS combined with post-processing using a multi-channel, recursive least squares (M-RLS) algorithm. This method needs to be developed further to enable practical utility; thus, WLMS combined with M-RLS currently provides the best compromise between EEG data quality and practicalities of motion detection

Exploring the advantages of multiband fMRI with simultaneous EEG to investigate coupling between gamma frequency neural activity and the BOLD response in humans

We established an optimal combination of EEG recording during sparse multiband (MB) fMRI that preserves high resolution, whole brain fMRI coverage whilst enabling broad-band EEG recordings which are uncorrupted by MRI gradient artefacts (GAs). We firstly determined the safety of simultaneous EEG recording during MB fMRI. Application of MB factor = 4 produced <1°C peak heating of electrode/hardware during 20-minutes of GE–EPI data acquisition. However, higher SAR sequences require specific safety testing, with greater heating observed using PCASL with MB factor =4. Heating was greatest in the electrocardiogram channel, likely due to it possessing longest lead length. We investigated the effect of MB factoron the temporal signal to noise ratio for a range of GE-EPI sequences (varying MB factor and temporal interval between slice acquisitions). We found that, for our experimental purpose, the optimal acquisition was achieved with MB factor=3, 3mm isotropic voxels and 33 slices providing whole head coverage. This sequence afforded a 2.25s duration quiet period (without GAs) in every 3s TR. Using this sequence we demonstrated the ability to record gamma frequency (55-80Hz) EEG oscillations, in response to right index finger abduction, that are usually obscured by Gas during continuous fMRI data acquisition. In this novel application of EEG - MB fMRI to a motor task we observed a positive correlation between gamma and BOLD responses in bilateral motor regions. These findings support and extend previous work regarding coupling between neural and haemodynamic measures of brain activity in humans and showcase the utility of EEG-MB fMRI for future investigations

Exploring the advantages of multiband fMRI with simultaneous EEG to investigate coupling between gamma frequency neural activity and the BOLD response in humans

We established an optimal combination of EEG recording during sparse multiband (MB) fMRI that preserves high resolution, whole brain fMRI coverage whilst enabling broad-band EEG recordings which are uncorrupted by MRI gradient artefacts (GAs). We firstly determined the safety of simultaneous EEG recording during MB fMRI. Application of MB factor = 4 produced <1°C peak heating of electrode/hardware during 20-minutes of GE–EPI data acquisition. However, higher SAR sequences require specific safety testing, with greater heating observed using PCASL with MB factor =4. Heating was greatest in the electrocardiogram channel, likely due to it possessing longest lead length. We investigated the effect of MB factoron the temporal signal to noise ratio for a range of GE-EPI sequences (varying MB factor and temporal interval between slice acquisitions). We found that, for our experimental purpose, the optimal acquisition was achieved with MB factor=3, 3mm isotropic voxels and 33 slices providing whole head coverage. This sequence afforded a 2.25s duration quiet period (without GAs) in every 3s TR. Using this sequence we demonstrated the ability to record gamma frequency (55-80Hz) EEG oscillations, in response to right index finger abduction, that are usually obscured by Gas during continuous fMRI data acquisition. In this novel application of EEG - MB fMRI to a motor task we observed a positive correlation between gamma and BOLD responses in bilateral motor regions. These findings support and extend previous work regarding coupling between neural and haemodynamic measures of brain activity in humans and showcase the utility of EEG-MB fMRI for future investigations

Spurious correlations in simultaneous EEG-fMRI driven by in-scanner movement

Simultaneous EEG-fMRI provides an increasingly attractive research tool to investigate cognitive processes with high temporal and spatial resolution. However, artifacts in EEG data introduced by the MR-scanner still remain a major obstacle. This study employing commonly used artifact correction steps shows that head motion, one overlooked major source of artifacts in EEG-fMRI data, can cause plausible EEG effects and EEG-BOLD correlations. Specifically, low frequency EEG

EEG signatures of auditory activity correlate with simultaneously recorded fMRI responses in humans

We recorded auditory-evoked potentials (AEPs) during simultaneous, continuous fMRI and identified trial-to-trial correlations between the amplitude of electrophysiological responses, characterised in the time domain and the time–frequency domain, and the hemodynamic BOLD response. Cortical AEPs were recorded from 30 EEG channels within the 3 T MRI scanner with and without the collection of simultaneous BOLD fMRI. Focussing on the Cz (vertex) EEG response, single-trial AEP responses were measured from time-domain waveforms. Furthermore, a novel method was used to characterise the single-trial AEP response within three regions of interest in the time–frequency domain (TF-ROIs). The latency and amplitude values of the N1 and P2 AEP peaks during fMRI scanning were not significantly different from the Control session (p > 0.16). BOLD fMRI responses to the auditory stimulation were observed in bilateral secondary auditory cortices as well as in the right precentral and postcentral gyri, anterior cingulate cortex (ACC) and supplementary motor cortex (SMC). Significant single-trial correlations were observed with a voxel-wise analysis, between (1) the magnitude of the EEG TF-ROI1 (70–800 ms post-stimulus, 1–5 Hz) and the BOLD response in right primary (Heschl's gyrus) and secondary (STG, planum temporale) auditory cortex; and (2) the amplitude of the P2 peak and the BOLD response in left pre- and postcentral gyri, the ACC and SMC. No correlation was observed with single-trial N1 amplitude on a voxel-wise basis. An fMRI-ROI analysis of functionally-identified auditory responsive regions identified further single-trial correlations of BOLD and EEG responses. The TF amplitudes in TF-ROI1 and TF-ROI2 (20–400 ms post-stimulus, 5–15 Hz) were significantly correlated with the BOLD response in all bilateral auditory areas investigated (planum temporale, superior temporal gyrus and Heschl's gyrus). However the N1 and P2 peak amplitudes, occurring at similar latencies did not show a correlation in these regions. N1 and P2 peak amplitude did correlate with the BOLD response in bilateral precentral and postcentral gyri and the SMC. Additionally P2 and TF-ROI1 both correlated with the ACC. TF-ROI3 (400–900 ms post-stimulus, 4–10 Hz) correlations were only observed in the ACC and SMC. Across the group, the subject-mean N1 peak amplitude correlated with the BOLD response amplitude in the primary and secondary auditory cortices bilaterally, as well as the right precentral gyrus and SMC. We confirm that auditory-evoked EEG responses can be recorded during continuous and simultaneous fMRI. We have presented further evidence of an empirical single-trial coupling between the EEG and BOLD fMRI responses, and show that a time–frequency decomposition of EEG signals can yield additional BOLD fMRI correlates, predominantly in auditory cortices, beyond those found using the evoked response amplitude alone

Simultane Erfassung von Verhaltensdaten, evozierten Potentialen und funktioneller MRT bei einer Aufgabe zur Verhaltenskontrolle

Ziel der Arbeit war die Untersuchung exekutiver Funktionen, in diesem Fall der Inhibition und der Volition, also der freien Entscheidung mittels simultaner EEG- und fMRT-Datenerhebung. Mit dem EEG lassen sich Datensätze mit einer hohen zeitlichen Auflösung generieren. Als neurophysiologisches Korrelat auf einen Stimulus erhält man sog. Ereignis korrelierte Potentiale (EKPs), die nach einer bestimmten Zeitdauer nach Stimuluspräsentation auftreten. Die räumliche Auflösung dieser Methode ist jedoch stark limitiert. Andererseits erhält man mit der fMRT Datensätze mit einer hohen räumlichen, jedoch geringen zeitlichen Auflösung. Mittels einer neuen Methode, der sog. Single-Trial-Koppelung können Datensätze generiert werden, die beide Modalitäten miteinander vereinen. Somit können Rückschlüsse über die zeitliche Aktivierung von Hirnarealen gezogen werden.15 gesunde Probanden nahmen an einem adaptierten, auditiven Go/NoGo-Paradigma teil, welches um eine Volitionsbedingung erweitert wurde. Es wurden Töne mit unterschiedlich hoher Frequenz demonstriert. Bei der Go-Bedingung (mittelhoch-hoch) mussten die Probanden so schnell wie möglich eine Reaktionstaste betätigen. Bei der NoGo-Bedingung (mittelhoch-tief) musssten sie dies unterlassen und bei der Volitionsbedingung (2x mittelhoch) mussten sie sich entscheiden, ob sie die Reaktionstaste drücken wollten oder nicht. Die fMRT-Auswertung erfolte mit dem Programm Brain Voyager, die EEG-Daten wurden zunächst mit EEGlab vorverarbeitet und dann mit dem Programm Brain Vision Analyzer analysiert. Bei der Single-Trial-Analyse wurden die EEG-Daten jedes einzelnen Durchgangs mit den BOLD-Veränderungen im fMRT korreliert. Technisch wurden dabei bei der Berechnung des sog. Allgemeinen Linearen Modells die Signaländerungen im EEG für bestimmte Zeiträume berücksichtigt. Auf diese Weise kann man Hirnregionen darstellen, bei denen die in der fMRT gemessenen Signaländerungen am stärksten mit der Signaländerung im EEG korrelieren. Die Single-Trial-Analyse wurde für das N2-Potential bei Volition und NoGo an der Elektrode Fz durchgeführt, für die P300 bei NoGo an Cz und für Volition und Go an Pz.Bei der Auswertung der hämodynamischen Daten zeigten sich für die Bedingung Volition gegen eine Kontrollbedingung Aktivierungen im Bereich der prä-SMA und des dorsolateralen präfrontalen Kortex (DLPFC). Elektrophysiologisch zeigte sich ein negatives Potential nach ca. 200ms (N2) und ein positives Potential nach ca. 300ms (P300). In der Single-Trial-Analyse zeigte sich, dass das N2-Potential während der Volitionsbedingung vornehmlich mit medio-frontalen Hirnregionen wie der SMA und lateral-frontalen Arealen assoziiert war. Das P300-Potential bot ebenfalls Aktiveriungen in lateral-frontalen Arealen und in der temporoparietalen Übergangszone. Bei der Inhibition von Verhalten zeigten sich bei Analyse der fMRT-Daten Aktiveriungen im Bereich des Gyrus frontalis superior und des DLPFC. Das N2-Potential war hier vornehmlich mit frontalen Bereichen wie dem DLPFC und dem ventro-lateralen präfrontalen Kortex (VLPFC) assoziiert. Das NoGo-P300-Potential hingegen lieferte Minderaktivierungen in allen für Motorik wichtigen Bereiche.Durch die direkte Korrelation von hämodynamischen und elektrophysiologischen Daten ist es uns gelungen, nicht nur diejenigen Hirnareale darzustellen, die bei den einzelnen Versuchsbedingungen aktiviert waren, sondern auch zu zeigen, wie es sich mit der zeitlichen Organisation innerhalb dieses neuronalen Netzwerkes verhält. Darüber hinaus konnten wir zeigen, dass die EKPs je nach Versuchsbedingung von unterschiedlichen Hirngeneratoren erzeugt wurden, was den Schluss zulässt, dass die EKPs abhängig von den jeweiligen Versuchsbedingungen sind und somit auch stets eine andere Funktion repräsentieren. Zudem konnten wir bei der Single-Trial-Analyse eine Beteiligung jener Hirnareale zeigen, welche auch bei der isolierten Auswertung der hämodynamischen Daten identifiziert werden konnten, was den Schluss zulässt, dass die Signale, die in beiden Modalitäten erzeugt wurden, zu einem großen Teil von denselben neuronalen Generatoren in Abhängigkeit der Versuchsbedingung erzeugt wurden

Attentional modulations of pain perception: evidence from laser evoked potentials

This thesis aims to provide a contribution to the current neurophysiological and psychophysiological understanding of nociception and pain processing in humans. The introduction of high-power, radiant heat stimulators (lasers) in sensory physiology has revolutionised the study of the nociceptive system. Laser pulses activate Aδ and/or C skin nociceptors selectively, i.e. without coactivating deeper, tactile mechanoreceptors, and elicit brain responses that can be detected using electroencephalography, and are called laser-evoked potentials (LEP). This was the technique applied in the two experimental studies reported in the present thesis work. The doctoral dissertation is organized in five chapters. Chapter 1 – Introduction - defines the concepts of nociception and pain. It also provides an introduction to the event related potential technique (ERP), a description of basic biophysics and neurophysiology related to LEP recording, followed by a literature review of its related cortical generators. In addition, the Chapter attempts to draw an elementary parallel between LEPs and other EPs elicited by stimuli belonging to other sensory modalities. Chapter 2 – Determinants of vertex potentials – describes the determinants of neural processes of pain perception and support their interpretation through a neurocognitive model of attention. The mechanism of attention allows allocating resources for selection and integration of this process with working memory requirements. More in detail, cognitive science suggested that the attention mechanism can be divided into two categories: stimulus-driven (or ‘bottom-up’) and goal-directed (or ‘top-down’). ‘Top-down’ and ‘bottom-up’ are treated as key interpretative categories to explain the findings reported in this thesis. Infact, they are metaphors which are used to represent information processing in a hierarchical fashion, where lower levels of processing would rely on the physical features of the stimulus while higher levels would involve comparisons with information stored in memory, selection of relevant information in competition and response to the stimulus. A review of selected literature in the field or ERP studies of sensory processing is provided and interpreted within this framework. The thesis aims to contribute to the understanding of both ‘bottom-up’ and ‘top-down’ mechanisms of attention during nociceptive processing, with two distinct experiments. Chapter 3 – Contribution to the analysis of ‘bottom-up features: “Dishabituation of laser-evoked EEG responses: dissecting the effect of certain and uncertain changes in stimulus modality” - presents a study where the hypothesis that a change of modality (from auditory to nociceptive and vicerversa, rather than no change at all) can significantly modulate brain responses (no matter the subjects expectation of this change) has been tested. The results of this study bring support for a determinant role of saliency (here modulated by the novelty introduced by a change in the stimulus modality) in affecting brain responses to the sensory input. Chapter 4 - Hypnotic modulation of sensory and affective dimensions of pain: a top-down signature on pain experience - introduces a study where hypnotic suggestions were used to draw subject’s attention either on intensity or on unpleasantness of pain perception. Thus, the study aimed to investigate whether this manipulation could induce a dissociation between this two measure of subjective experience and whether LEP could reflect the role of focused attention and expectation in indexing changes of subjective feeling. The results are discussed according to previous literature and to a neurocognitive model of pain processing as observed during an altered state of consciousness known to heighten the fronto-parietal network of sustained attention. In Chapter 5 - General discussion - the findings related to these two different research lines are integrated and discussed considering the existing theoretical accounts. The critical assumption is that the understanding of pain processing would largely benefit from the application of an attention-driven interpretative framework within which can be included different theoretical-epistemological views concerning (II) the Bayesian inference in perception, (III) the motivational account of pain monitoring and control, (IV) the neuroanatomy of homeostatic feeling of body integrity and self-regulation. As conclusive remark, the work presented in this thesis wish to highlight the importance of a renewed concept of ‘pain matrix’, based on its function of potential threat detector and action planner, in order to preserve the integrity of the body. In addition, the interpretation of pain as homeostatic-motivational force naturally carries us to consider the ‘pain matrix’ not as a sensory-specific cortical network but rather as an action-specific network, representing the activity by which the individual identifies and responds purposefully to a sudden, potential threat inside or outside of the body

Neural correlates of auditory perceptual organization measured with direct cortical recordings in humans

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, September 2011."August, 2011." Vita. Cataloged from PDF version of thesis.Includes bibliographical references.One of the primary functions of the human auditory system is to separate the complex mixture of sound arriving at the ears into neural representations of individual sound sources. This function is thought to be crucial for survival and communication in noisy settings, and allows listeners to selectively and dynamically attend to a sound source of interest while suppressing irrelevant information. How the brain works to perceptually organize the acoustic environment remains unclear despite the multitude of recent studies utilizing microelectrode recordings in experimental animals or non-invasive human neuroimaging. In particular, the role that brain areas outside the auditory cortex might play is, comparatively, vastly understudied. The experiments described in this thesis combined classic behavioral paradigms with electrical recordings made directly from the cortical surface of neurosurgical patients undergoing clinically-indicated invasive monitoring for localization of epileptogenic foci. By sampling from widespread brain areas with high temporal resolution while participants simultaneously engaged in streaming and jittered multi-tone masking paradigms, the present experiments sought to overcome limitations inherent in previous work, namely sampling extent, resolution in time and space, and direct knowledge of the perceptual experience of the listener. In experiment 1, participants listened to sequences of tones alternating in frequency (i.e., ABA-) and indicated whether they perceived the tones as grouped ("1 stream") or segregated ("2 streams"). As has been reported in neurologically-normal listeners since the 1950s, patients heard the sequences as grouped when the frequency separation between the A and B tones was small and segregated when it was large. Evoked potentials from widespread brain areas showed amplitude correlations with frequency separation but surprisingly did not differ based solely on perceptual organization in the absence of changes in the stimuli. In experiment 2, participants listened to sequences of jittered multi-tone masking stimuli on which a regularly-repeating target stream of tones was sometimes superimposed and indicated when they heard the target stream. Target detectability, as indexed behaviorally, increased throughout the course of each sequence. Evoked potentials and high-gamma activity differed strongly based on the listener's subjective perception of the target tones. These results extend and constrain theories of how the brain subserves auditory perceptual organization and suggests several new avenues of research for understanding the neural mechanisms underlying this critical function.by Andrew R. Dykstra.Ph.D