Richard A.J. Masterton

The core network in absence epilepsy Differences in cortical and thalamic BOLD response

Objectives: We used EEG-fMRI to study epileptiform activity in a cohort of untreated children with typical absence seizures (AS). Our aim was to identify cortical and subcortical regions involved in spike and wave events and to explore the timing of activity in these regions. Methods: Eleven children with AS confirmed on video-EEG underwent EEG-fMRI. An event-related analysis of epileptiform activity was performed. Regions of interest (ROIs), identified in the event-related analysis, were used to study the time course of the blood oxygen level–dependent (BOLD) signal prior to and immediately following events of interest in these ROIs. Results: Group analysis confirmed positive BOLD in the thalamus and negative BOLD in the lateral and mesial parietal lobe, caudate nuclei, and additionally the brainstem reticular formation. The event-related time course differed between the thalamus, the parietal cortex, and the pons and caudate nuclei. In the subcortical structures, BOLD signal change occurred at, or immediately after, electrographic onset. Importantly, in the parietal cortex, but not in other cortical regions, there was a subtle BOLD signal increase for 10 seconds prior to the onset of epileptiform activity. Conclusions: In children with typical AS, we have confirmed a core network of structures involved in generalized epileptiform activity that includes the reticular structures of the brainstem. Furthermore, we have identified changes in parietal BOLD signal which precede the onset of epileptiform activity, suggesting the parietal cortex has a role in the initiation of epileptiform activity.

Measurement and reduction of motion and ballistocardiogram artefacts from simultaneous EEG and fMRI recordings.

Recording the electroencephalogram (EEG) during functional magnetic resonance imaging (fMRI) permits the identification of haemodynamic changes associated with EEG events. However, subject motion within the MR scanner can cause unpredictable and frustrating artefacts on the EEG that may appear focally, bilaterally or unilaterally and can sometimes be confused for epileptiform activity. Motion may arise from a number of sources: small involuntary cardiac-related body movements (ballistocardiogram); acoustic vibrations due to the scanner machinery; and voluntary subject movements. Here we describe a new real-time technique for removing ballistocardiogram (BCG) and movement artefact from EEG recordings in the MR scanner using a novel method for recording subject motion. We record the current induced in a number of wire loops, attached to a cap worn by the subject, due to motion in the static magnetic field of the scanner (Faradays Law). This is the same process that leads to the motion artefacts on the EEG, and hence these signals are ideally suited to filtering these artefacts from the EEG. Our filter uses a linear adaptive technique based upon the Recursive Least Squares (RLS) algorithm. We demonstrate in both simulations and real EEG recordings from epilepsy patients that our filter significantly reduces the artefact power whilst preserving the underlying EEG signal.

Focal epileptiform spikes do not show a canonical BOLD response in patients with benign rolandic epilepsy (BECTS).

Simultaneous EEG and functional MRI (EEG-fMRI) studies of focal epileptiform spikes commonly use the canonical haemodynamic response function (HRF) to model the blood-oxygenation-level-dependent (BOLD) response to these events. Support for the use of the canonical HRF has come from large studies that contain mixed cohorts of epilepsy syndromes and discharge types, and has demonstrated plausible epileptic localisation results in the majority of patients. Other studies, however, have reported that some patients show a BOLD response that differs markedly from a canonical HRF. Our aim in this study was to see if the BOLD response is well modelled by a canonical HRF in a homogeneous cohort of patients with benign epilepsy with centrotemporal spikes (BECTS), an idiopathic partial epilepsy with stereotypical centrotemporal spikes on the EEG. We studied eight well-characterised and typical BECTS patients and found that the shape of the average BOLD response was different to the canonical HRF. Furthermore, a localisation analysis using the group-average response provided increased sensitivity and specificity compared to the canonical HRF. Our findings suggest that the canonical HRF may not provide the best model for the BOLD response in some epilepsy syndromes or spike-types. In studies of homogeneous patient groups, therefore, localisation results may be improved by using a group-specific BOLD response.

The frontal lobe in absence epilepsy: EEG-fMRI findings.

Objective: Studies of absence seizures (AS) using EEG with fMRI (EEG-fMRI) show a consistent network with prominent thalamic activation and a variety of cortical changes. Despite evidence suggesting a role of frontal cortex in seizure generation, group studies have not detected consistent AS-related changes in this region. We hypothesized that only a subgroup may show frontal cortical activation. Method: We studied 13 subjects with AS during EEG-fMRI to classify the different individual patterns of frontal cortical activation associated with AS. Results: Based upon visual inspection of surface-rendered activation maps we identified 2 subgroups that could be distinguished by the activation in the dorsolateral prefrontal cortex (DLPFC). One group of patients (n = 7) showed a primarily positive signal change (DLPFC-POS), whereas the other group (n = 6) showed a primarily negative signal change (DLFPC-NEG). When the DLPFC-POS group was compared to the DLPFC-NEG group, time-course analysis revealed a larger positive blood oxygenation level–dependent deflection following onset of the AS in cortical and subcortical areas beyond the DLPFC. This suggests a basic biological difference between these groups. Conclusion: These observations suggest that there may be at least 2 mechanisms underpinning AS in individuals with absence epilepsy. This may have phenotypic and genetic implications for understanding epilepsy syndromes.

Relationship between language lateralization and handedness in left-hemispheric partial epilepsy

Objective: To investigate the relationship between language lateralization and handedness in patients with epilepsy and a left-sided seizure focus and in healthy control subjects. Methods: We recruited a consecutive series of 74 patients and 70 control subjects. Functional MRI, using a noun–verb generation task, was performed to establish the language laterality index (LI). Handedness was quantified using the Edinburgh Handedness Inventory. Results: Patients showed a shift toward atypical language lateralization (0.43 ± 0.47; controls 0.57 ± 034; p ≤ 0.05) and left-handedness (55 ± 57; controls 74 ± 39; p ≤ 0.05). The LI and handedness were correlated in patients (r = 0.54; F = 25.9; p < 0.001) but not in control subjects (r = 0.1; F = 0.64; NS). A combination of left-handedness and atypical LI was more frequent in patients (12%) than control subjects (0%; p ≤ 0.05). Crossed hemispheric specialization (e.g., right-handedness associated with atypical LI) was equally frequent in patients (20%) and control subjects (16%; NS). Conclusion: In epilepsy patients with a left-sided seizure focus, language lateralization is correlated to handedness. The increased frequency of left-handedness and associated atypical language lateralization is most likely related to the left-hemispheric seizure focus, influencing hemispheric specialization for both domains.

Track-weighted functional connectivity (TW-FC): a tool for characterizing the structural-functional connections in the brain.

MRI provides a powerful tool for studying the functional and structural connections in the brain non-invasively. The technique of functional connectivity (FC) exploits the intrinsic temporal correlations of slow spontaneous signal fluctuations to characterise brain functional networks. In addition, diffusion MRI fibre-tracking can be used to study the white matter structural connections. In recent years, there has been considerable interest in combining these two techniques to provide an overall structural-functional description of the brain. In this work we applied the recently proposed super-resolution track-weighted imaging (TWI) methodology to demonstrate how whole-brain fibre-tracking data can be combined with FC data to generate a track-weighted (TW) FC map of FC networks. The method was applied to data from 8 healthy volunteers, and illustrated with (i) FC networks obtained using a seeded connectivity-based analysis (seeding in the precuneus/posterior cingulate cortex, PCC, known to be part of the default mode network), and (ii) with FC networks generated using independent component analysis (in particular, the default mode, attention, visual, and sensory-motor networks). TW-FC maps showed high intensity in white matter structures connecting the nodes of the FC networks. For example, the cingulum bundles show the strongest TW-FC values in the PCC seeded-based analysis, due to their major role in the connection between medial frontal cortex and precuneus/posterior cingulate cortex; similarly the superior longitudinal fasciculus was well represented in the attention network, the optic radiations in the visual network, and the corticospinal tract and corpus callosum in the sensory-motor network. The TW-FC maps highlight the white matter connections associated with a given FC network, and their intensity in a given voxel reflects the functional connectivity of the part of the nodes of the network linked by the structural connections traversing that voxel. They therefore contain a different (and novel) image contrast from that of the images used to generate them. The results shown in this study illustrate the potential of the TW-FC approach for the fusion of structural and functional data into a single quantitative image. This technique could therefore have important applications in neuroscience and neurology, such as for voxel-based comparison studies.

Mapping brain activity using event-related independent components analysis (eICA): Specific advantages for EEG-fMRI

Event-related analyses of functional MRI (fMRI) typically assume that the onset and offset of neuronal activity match stimuli onset and offset, and that evoked fMRI signal changes follow the canonical haemodynamic response function (HRF). Some event types, however, may be unsuited to this approach: brief stimuli might elicit an extended neuronal response; anticipatory effects might result in activity preceding the event; or altered neurovascular coupling may result in a non-canonical HRF. An example is interictal epileptiform discharges (IEDs), which may show a non-canonical HRF and fMRI signal changes preceding their onset as detected on EEG. In such cases, less constrained analyses - capable of detecting early, non-canonical responses - may be necessary. A consequence of less constrained analyses, however, is that artefactual sources of signal change - motion or physiological noise for example - may also be detected and mixed with the neuronally-generated signals. In this paper, to address this issue, we describe an event-related independent components analysis (eICA) that identifies different sources of event-related signal change that can then be separately assessed to identify likely artefacts and separate primary from propagated activity. We also describe a group analysis that identifies eICA components that are spatially and temporally consistent across subjects and provides an objective approach for selecting group-specific components likely to be of neural origin. We apply eICA to patients with rolandic epilepsy - with stereotypical IEDs arising from a focus in the rolandic fissure - and demonstrate that a single event-related component, concordant with this source location, is detected.

Lennox-Gastaut syndrome and phenotype: Secondary network epilepsies

Lennox‐Gastaut syndrome (LGS) is a severe epilepsy phenotype with characteristic electroclinical features despite diverse etiologies. We previously found common cerebral networks involved during slow spike‐and‐wave (SSW) and generalized paroxysmal fast activity (PFA), characteristic interictal discharges. Some patients have a Lennox‐Gastaut–like phenotype and cortical lesions. We wished to explore the interaction between cerebral networks and lesions in this group.

Absence epilepsy subnetworks revealed by event-related independent components analysis of functional magnetic resonance imaging

The aim of this study was to provide better spatiotemporal description of the brain activity observed during generalized spike‐and‐wave (GSW) discharges. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG‐fMRI) studies of these epileptiform events have shown regional differences in the timing of fMRI signal changes, which suggests activities within multiple interacting networks rather than a single unified network.

Hippocampal sclerosis: MR prediction of seizure intractability.

Summary:  Purpose: Patients with refractory temporal lobe epilepsy (refractory TLE) often have hippocampal sclerosis (HS). However, some HS patients have less‐severe, drug‐responsive epilepsy (mild TLE). We investigated the pattern of MR changes in these two HS groups.