David W. Carmichael

Recent advances in recording electrophysiological data simultaneously with magnetic resonance imaging

Simultaneous recording of brain activity by different neurophysiological modalities can yield insights that reach beyond those obtained by each technique individually, even when compared to those from the post-hoc integration of results from each technique recorded sequentially. Success in the endeavour of real-time multimodal experiments requires special hardware and software as well as purpose-tailored experimental design and analysis strategies. Here, we review the key methodological issues in recording electrophysiological data in humans simultaneously with magnetic resonance imaging (MRI), focusing on recent technical and analytical advances in the field. Examples are derived from simultaneous electroencephalography (EEG) and electromyography (EMG) during functional MRI in cognitive and systems neuroscience as well as in clinical neurology, in particular in epilepsy and movement disorders. We conclude with an outlook on current and future efforts to achieve true integration of electrical and haemodynamic measures of neuronal activity using data fusion models.

Noncanonical spike-related BOLD responses in focal epilepsy

Till now, most studies of the Blood Oxygen Level‐Dependent (BOLD) response to interictal epileptic discharges (IED) have assumed that its time course matches closely to that of brief physiological stimuli, commonly called the canonical event‐related haemodynamic response function (canonical HRF). Analyses based on that assumption have produced significant response patterns that are generally concordant with prior electroclinical data. In this work, we used a more flexible model of the event‐related response, a Fourier basis set, to investigate the presence of other responses in relation to individual IED in 30 experiments in patients with focal epilepsy. We found significant responses that had a noncanonical time course in 37% of cases, compared with 40% for the conventional, canonical HRF‐based approach. In two cases, the Fourier analysis suggested activations where the conventional model did not. The noncanonical activations were almost always remote from the presumed generator of epileptiform activity. In the majority of cases with noncanonical responses, the noncanonical responses in single‐voxel clusters were suggestive of artifacts. We did not find evidence for IED‐related noncanonical HRFs arising from areas of pathology, suggesting that the BOLD response to IED is primarily canonical. Noncanonical responses may represent a number of phenomena, including artefacts and propagated epileptiform activity. Hum Brain Mapp 2008.

Independent component analysis of interictal fMRI in focal epilepsy: Comparison with general linear model-based EEG-correlated fMRI

The general linear model (GLM) has been used to analyze simultaneous EEG-fMRI to reveal BOLD changes linked to interictal epileptic discharges (IED) identified on scalp EEG. This approach is ineffective when IED are not evident in the EEG. Data-driven fMRI analysis techniques that do not require an EEG derived model may offer a solution in these circumstances. We compared the findings of independent components analysis (ICA) and EEG-based GLM analyses of fMRI data from eight patients with focal epilepsy. Spatial ICA was used to extract independent components (IC) which were automatically classified as either BOLD-related, motion artefacts, EPI-susceptibility artefacts, large blood vessels, noise at high spatial or temporal frequency. The classifier reduced the number of candidate IC by 78%, with an average of 16 BOLD-related IC. Concordance between the ICA and GLM-derived results was assessed based on spatio-temporal criteria. In each patient, one of the IC satisfied the criteria to correspond to IED-based GLM result. The remaining IC were consistent with BOLD patterns of spontaneous brain activity and may include epileptic activity that was not evident on the scalp EEG. In conclusion, ICA of fMRI is capable of revealing areas of epileptic activity in patients with focal epilepsy and may be useful for the analysis of EEG-fMRI data in which abnormalities are not apparent on scalp EEG.

Epileptic networks in focal cortical dysplasia revealed using electroencephalography–functional magnetic resonance imaging

Surgical treatment of focal epilepsy in patients with focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural magnetic resonance imaging (MRI), so intracranial electroencephalography (icEEG) is needed to delineate the seizure onset zone (SOZ). EEG‐functional MRI (fMRI) can reveal interictal discharge (IED)‐related hemodynamic changes in the irritative zone (IZ). We assessed the value of EEG‐fMRI in patients with FCD‐associated focal epilepsy by examining the relationship between IED‐related hemodynamic changes, icEEG findings, and postoperative outcome.

Functional MRI with active, fully implanted, deep brain stimulation systems: Safety and experimental confounds

We investigated safety issues and potential experimental confounds when performing functional magnetic resonance imaging (fMRI) investigations in human subjects with fully implanted, active, deep brain stimulation (DBS) systems. Measurements of temperature and induced voltage were performed in an in vitro arrangement simulating bilateral DBS during magnetic resonance imaging (MRI) using head transmit coils in both 1.5 and 3.0 T MRI systems. For MRI sequences typical of an fMRI study with coil-averaged specific absorption rates (SARs) less than 0.4 W/kg, no MRI-induced temperature change greater than the measurement sensitivity (0.1 degrees C) was detected at 1.5 T, and at 3 T temperature elevations were less than 0.5 degrees C, i.e. within safe limits. For the purposes of demonstration, MRI pulse sequences with SARs of 1.45 W/kg and 2.34 W/kg (at 1.5 T and 3 T, respectively) were prescribed and elicited temperature increases (>1 degrees C) greater than those considered safe for human subjects. Temperature increases were independent of the presence or absence of active stimulator pulsing. At both field strengths during echo planar MRI, the perturbations of DBS equipment performance were sufficiently slight, and temperature increases sufficiently low to suggest that thermal or electromagnetically mediated experimental confounds to fMRI with DBS are unlikely. We conclude that fMRI studies performed in subjects with subcutaneously implanted DBS units can be both safe and free from DBS-specific experimental confounds. Furthermore, fMRI in subjects with fully implanted rather than externalized DBS stimulator units may offer a significant safety advantage. Further studies are required to determine the safety of MRI with DBS for other MRI systems, transmit coil configurations and DBS arrangements.

Electrophysiological correlates of the BOLD signal for EEG-informed fMRI

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG–fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level‐dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological–haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals and proceed by reviewing EEG‐informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (EEG–fMRI mapping), or exploring a range of EEG‐derived quantities to determine which best explain colocalised BOLD fluctuations (local EEG–fMRI coupling). While reviewing studies of different forms of brain activity (epileptic and nonepileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG‐informed fMRI. Our review is focused on EEG‐informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG‐informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG–fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations. Hum Brain Mapp, 36:391–414, 2015.

Network Connectivity in Epilepsy: Resting State fMRI and EEG–fMRI Contributions

There is a growing body of evidence pointing toward large-scale networks underlying the core phenomena in epilepsy, from seizure generation to cognitive dysfunction or response to treatment. The investigation of networks in epilepsy has become a key concept to unlock a deeper understanding of the disease. Functional imaging can provide valuable information to characterize network dysfunction; in particular resting state fMRI (RS-fMRI), which is increasingly being applied to study brain networks in a number of diseases. In patients with epilepsy, network connectivity derived from RS-fMRI has found connectivity abnormalities in a number of networks; these include the epileptogenic, cognitive and sensory processing networks. However, in majority of these studies, the effect of epileptic transients in the connectivity of networks has been neglected. EEG–fMRI has frequently shown networks related to epileptic transients that in many cases are concordant with the abnormalities shown in RS studies. This points toward a relevant role of epileptic transients in the network abnormalities detected in RS-fMRI studies. In this review, we summarize the network abnormalities reported by these two techniques side by side, provide evidence of their overlapping findings, and discuss their significance in the context of the methodology of each technique. A number of clinically relevant factors that have been associated with connectivity changes are in turn associated with changes in the frequency of epileptic transients. These factors include different aspects of epilepsy ranging from treatment effects, cognitive processes, or transition between different alertness states (i.e., awake–sleep transition). For RS-fMRI to become a more effective tool to investigate clinically relevant aspects of epilepsy it is necessary to understand connectivity changes associated with epileptic transients, those associated with other clinically relevant factors and the interaction between them, which represents a gap in the current literature. We propose a framework for the investigation of network connectivity in patients with epilepsy that can integrate epileptic processes that occur across different time scales such as epileptic transients and disease duration and the implications of this approach are discussed.

Safety of localizing epilepsy monitoring intracranial electroencephalograph electrodes using MRI: Radiofrequency-induced heating

To investigate heating during postimplantation localization of intracranial electroencephalograph (EEG) electrodes by MRI.

Simultaneous intracranial EEG-fMRI in humans: Protocol considerations and data quality

We have recently performed simultaneous intracranial EEG and fMRI recordings (icEEG-fMRI) in patients with epilepsy. In this technical note, we examine limited thermometric data for potential electrode heating during our protocol and found that heating was ≤0.1 °C in-vitro at least 10 fold less than in-vivo limits. We quantify EEG quality, which can be degraded by MRI scanner-induced artefacts, and fMRI image (gradient echo echo-planar imaging: GE-EPI) signal quality around the electrodes, which can be degraded by electrode interactions with B1 (radiofrequency) and B0 (static) magnetic fields. We recorded EEG outside and within the MRI scanner with and without scanning. EEG quality was largely preserved during scanning and in particular heartbeat-related artefacts were small compared to epileptic events. To assess the GE-EPI signal reduction around the electrodes, we compared image signal intensity along paths into the brain normal to its surface originating from the individual platinum-iridium electrode contacts. GE-EPI images were obtained at 1.5 T with an echo time (TE) of 40 ms and repetition time (TR) of 3000 ms and a slice thickness of 2.5 mm. We found that GE-EPI signal intensity reduction was confined to a 10 mm radius and that it was reduced on average by less than 50% at 5mm from the electrode contacts. The GE-EPI image signal reduction also varied with electrode orientation relative to the MRI scanner axes; in particular, cortical grid contacts with a normal along the scanners main magnetic field (B(0)) axis have higher artefact levels relative to those with a normal perpendicular to the z-axis. This suggests that the artefacts were predominantly susceptibility-related rather than due to B1 interactions. This information can be used to guide interpretation of results of icEEG-fMRI experiments proximal to the electrodes, and to optimise artefact reduction strategies.

Networks involved in seizure initiation A reading epilepsy case studied with EEG-fMRI and MEG

Objective: To define the ictal cortical/subcortical network of reading-induced seizures. Methods: We analyzed ictal magnetoencephalography (MEG) and EEG-correlated fMRI (EEG-fMRI) data in a unique patient with reading epilepsy (RE) affected by frequent perioral reflex myocloni triggered by reading silently. Results: Ictal MEG corroborated EEG localization and revealed activity extending precentrally into Brodmann area (BA) 6. fMRI blood oxygen level−dependent (BOLD) signal changes in the left deep piriform cortex (PFC) and left BA6 preceded seizures and occurred before BOLD changes were observed in thalamus and right inferior frontal gyrus (BA44). Dynamic causal modeling provided evidence of a causal link between hemodynamic changes in the left PFC and reading-evoked seizures. Conclusion: Our findings support the important role of deep cortical and subcortical structures, in particular the frontal PFC, as key regions in initiating and modulating seizure activity. In our patient with RE, BA6 appeared to be the area linking cognitive activation and seizure activity.