Umair J. Chaudhary

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.

Mapping hemodynamic correlates of seizures using fMRI: A review

Functional magnetic resonance imaging (fMRI) is able to detect changes in blood oxygenation level associated with neuronal activity throughout the brain. For more than a decade, fMRI alone or in combination with simultaneous EEG recording (EEG‐fMRI) has been used to investigate the hemodynamic changes associated with interictal and ictal epileptic discharges. This is the first literature review to focus on the various fMRI acquisition and data analysis methods applied to map epileptic seizure‐related hemodynamic changes from the first report of an fMRI scan of a seizure to the present day. Two types of data analysis approaches, based on temporal correlation and data driven, are explained and contrasted. The spatial and temporal relationship between the observed hemodynamic changes using fMRI and other non‐invasive and invasive electrophysiological and imaging data is considered. We then describe the role of fMRI in localizing and exploring the networks involved in spontaneous and triggered seizure onset and propagation. We also discuss that fMRI alone and combined with EEG hold great promise in the investigation of seizure‐related hemodynamic changes non‐invasively in humans. We think that this will lead to significant improvements in our understanding of seizures with important consequences for the treatment of epilepsy. Hum Brain Mapp, 2013.

Improving the sensitivity of EEG-fMRI studies of epileptic activity by modelling eye blinks, swallowing and other video-EEG detected physiological confounds

RATIONALE To improve the sensitivity and specificity of simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) it is prudent to devise modelling strategies explaining the residual variance. The purpose of this study is to investigate the potential value of including additional regressors for physiological activities, derived from video-EEG, in the modelling of haemodynamic patterns linked to interictal epileptiform discharges (IEDs) using simultaneously recorded video-EEG-fMRI. METHODS Ten patients with IED (focal epilepsy: 6, idiopathic generalized epilepsy (IGE):4) were studied. BOLD-sensitive fMRI images were acquired on a 3T MRI scanner. 64-channel EEG was recorded using MR-compatible system. A custom made, dual-video-camera system synchronised with EEG was used to record video simultaneously. IEDs and physiological activities were identified and labelled on video-EEG using Brain Analyzer2. fMRI time-series data were pre-processed and analysed using SPM5 software. Two general linear models (GLM) were created; GLM1: IEDs were convolved with the canonical haemodynamic response function and its derivatives. Realignment parameters and pulse regressors were included in the design matrix as confounds, GLM2: GLM1 and additional regressors identified on video-EEG including: eye blinks, hand or foot movement, chewing and swallowing were also included in the design matrix. SPM [F] maps (p<0.05, corrected for family wise error and p<0.001, uncorrected) were generated for both models. We compared the resulting blood oxygen level dependent (BOLD) maps for cluster size, statistical significance and degree of concordance with the irritative zone. RESULTS BOLD changes relating to physiological activities were generally seen in expected brain areas. In patients with focal epilepsy, the extent and Z-score of the IED-related global maximum BOLD clusters increased in 4/6 patients and additional IED-related BOLD clusters were observed in 3/6 patients for GLM2. Also, the degree of concordance of IED-related maps with irritative zone improved for one patient for GLM2 and was unchanged for the other cases. In patients with IGE, the size and statistical significance for global maximum and other BOLD clusters increased in 2/4 patients. We conclude that the inclusion of additional regressors, derived from video based information, in the design matrix explains a greater amount of variance and can reveal additional IED-related BOLD clusters which may be part of the epileptic networks.

Methods and utility of EEG-fMRI in epilepsy

Brain activity data in general and more specifically in epilepsy can be represented as a matrix that includes measures of electrophysiology, anatomy and behaviour. Each of these sub-matrices has a complex interaction depending upon the brain state i.e., rest, cognition, seizures and interictal periods. This interaction presents significant challenges for interpretation but also potential for developing further insights into individual event types. Successful treatments in epilepsy hinge on unravelling these complexities, and also on the sensitivity and specificity of methods that characterize the nature and localization of underlying physiological and pathological networks. Limitations of pharmacological and surgical treatments call for refinement and elaboration of methods to improve our capability to localise the generators of seizure activity and our understanding of the neurobiology of epilepsy. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI), by potentially circumventing some of the limitations of EEG in terms of sensitivity, can allow the mapping of haemodynamic networks over the entire brain related to specific spontaneous and triggered epileptic events in humans, and thereby provide new localising information. In this work we review the published literature, and discuss the methods and utility of EEG-fMRI in localising the generators of epileptic activity. We draw on our experience and that of other groups, to summarise the spectrum of information provided by an increasing number of EEG-fMRI case-series, case studies and group studies in patients with epilepsy, for its potential role to elucidate epileptic generators and networks. We conclude that EEG-fMRI provides a multidimensional view that contributes valuable clinical information to localize the epileptic focus with potential important implications for the surgical treatment of some patients with drug-resistant epilepsy, and insights into the resting state and cognitive network dynamics.

Generalized Spike and Waves: Effect of Discharge Duration on Brain Networks as Revealed by BOLD fMRI

In the past decade, the possibility of combining recordings of EEG and functional MRI (EEG–fMRI), has brought a new insight into the brain network underlying generalized spike wave discharges (GSWD). Nevertheless, how GSWD duration influences this network is not fully understood. In this study we aim to investigate whether GSWD duration had a threshold (non-linear) and/or a linear effect on the amplitude of the associated BOLD changes in any brain regions. This could help in elucidating if there is an hemodynamic background supporting the differentiation between interictal and ictal events. We studied a population of 42 patients with idiopathic generalized epilepsies (IGE) who underwent resting-state EEG–fMRI recordings in three centres (London, UK; Modena, Italy; Rome, Italy), applying a parametric analysis of the GSWD duration. Patients were classified as having Childhood Absence epilepsy, Juvenile Absence Epilepsy, or Juvenile Myoclonic Epilepsy. At the population level linear GSWD duration-related BOLD signal changes were found in a network of brain regions: mainly BOLD increase in thalami and cerebral ventricles, and BOLD decrease in posterior cingulate, precuneus and bilateral parietal regions. No region of significant BOLD change was found in the group analysis for the non-linear effect of GSWD duration. To explore the possible effect of both the different IGE sub-syndromes and the different protocols and scanning equipment used in the study, a full-factorial ANOVA design was performed revealing no significant differences. These findings support the idea that the amplitude of the BOLD changes is linearly related to the GSWD duration with no universal threshold effect of spike and wave duration on the brain network supporting this activity.

Imaging the interaction: epileptic discharges, working memory, and behavior.

Interictal generalized epileptiform discharges may impair cognition. We used simultaneous video‐electroencephalography and functional imaging to quantify changes, induced by epileptiform discharges, in the task‐related activations during a spatial working‐memory paradigm. The number of epileptiform discharges increased during the task with its level of complexity, but were not significantly associated with wrong responses during the task. We observed hemodynamic responses in working‐memory related frontal‐lobe‐network, motor‐cortex, precuneus, and parietal lobes in the absence of epileptiform discharges. In the presence of epileptiform discharges during the task, task‐related hemodynamic changes were seen only in motor‐cortex, precuneus, and parietal lobes. These findings suggest that generalized epileptiform discharges during a high demanding working memory task may change the working memory‐related hemodynamic responses in frontal‐lobe‐network. Hum Brain Mapp 34:2910–2917, 2013.

Implementation and evaluation of simultaneous video-electroencephalography and functional magnetic resonance imaging.

The objective of this study was to demonstrate that the addition of simultaneous and synchronised video to electroencephalography (EEG)-correlated functional magnetic resonance imaging (fMRI) could increase recorded information without data quality reduction. We investigated the effect of placing EEG, video equipment and their required power supplies inside the scanner room, on EEG, video and MRI data quality, and evaluated video-EEG-fMRI by modelling a hand motor task. Gradient-echo, echo-planner images (EPI) were acquired on a 3-T MRI scanner at variable camera positions in a test object [with and without radiofrequency (RF) excitation], and human subjects. EEG was recorded using a commercial MR-compatible 64-channel cap and amplifiers. Video recording was performed using a two-camera custom-made system with EEG synchronization. An in-house script was used to calculate signal to fluctuation noise ratio (SFNR) from EPI in test object with variable camera positions and in human subjects with and without concurrent video recording. Five subjects were investigated with video-EEG-fMRI while performing hand motor task. The fMRI time series data was analysed using statistical parametric mapping, by building block design general linear models which were paradigm prescribed and video based. Introduction of the cameras did not alter the SFNR significantly, nor did it show any signs of spike noise during RF off conditions. Video and EEG quality also did not show any significant artefact. The Statistical Parametric Mapping{T} maps from video based design revealed additional blood oxygen level-dependent responses in the expected locations for non-compliant subjects compared to the paradigm prescribed design. We conclude that video-EEG-fMRI set up can be implemented without affecting the data quality significantly and may provide valuable information on behaviour to enhance the analysis of fMRI data.

Phase–amplitude coupling and the BOLD signal: A simultaneous intracranial EEG (icEEG) - fMRI study in humans performing a finger-tapping task

Abstract Although it has been consistently found that local blood‐oxygen‐level‐dependent (BOLD) changes are better modelled by a combination of the power of multiple EEG frequency bands rather than by the power of a unique band alone, the local electro‐haemodynamic coupling function is not yet fully characterised. Electrophysiological studies have revealed that the strength of the coupling between the phase of low‐ and the amplitude of high‐ frequency EEG activities (phase–amplitude coupling ‐ PAC) has an important role in brain function in general, and in preparation and execution of movement in particular. Using electrocorticographic (ECoG) and functional magnetic resonance imaging (fMRI) data recorded simultaneously in humans performing a finger‐tapping task, we investigated the single‐trial relationship between the amplitude of the BOLD signal and the strength of PAC and the power of &agr;, &bgr;, and &ggr; bands, at a local level. In line with previous studies, we found a positive correlation for the &ggr; band, and negative correlations for the PAC&bgr;&ggr; strength, and the &agr; and &bgr; bands. More importantly, we found that the PAC&bgr;&ggr; strength explained variance of the amplitude of the BOLD signal that was not explained by a combination of the &agr;, &bgr;, and &ggr; band powers. Our main finding sheds further light on the distinct nature of PAC as a functionally relevant mechanism and suggests that the sensitivity of EEG‐informed fMRI studies may increase by including the PAC strength in the BOLD signal model, in addition to the power of the low‐ and high‐ frequency EEG bands. HighlightsFirst study of single‐trial correlations between the phase amplitude coupling strength and BOLD.Intracranial EEG and fMRI data simultaneously recorded in humans during a motor task.PAC&bgr;&ggr; strength explains variance of BOLD in addition a combination of &agr;, &bgr;, and &ggr; band powers.

A dialogue with historical concepts of epilepsy from the Babylonians to Hughlings Jackson: persistent beliefs.

Epilepsy is one of the few neurological disorders to be recognized in Antiquity. The etiology of epilepsy has evolved from affliction of evil spirits and bad omens to an organic disease of the brain. Geographically separate cultures have recognized the diverse symptomatology of epilepsy from vigorous convulsions to spontaneous localized jerking since times immemorial. Similarly, the diagnostic procedures and treatment options have varied in different milieus. In this review we have followed the course of history chronologically from Babylonians to Hughlings Jackson, mapping the conceptual development of epilepsy and the origin of some of the positive and negative attitudes inherited into todays epileptology. Original writings, such as Hughlings Jacksons letters, and English translations of early Latin work, where available, were used as primary sources of information. Where primary sources were not accessible, we consulted research articles, books, and commentaries by eminent historians and epileptologists.

Epilepsy causing pupillary hippus: an unusual semiology

Altered pupillary behavior is commonly present during and following epileptic seizures, but symptomatic pupillary hippus as the main feature of a seizure has not been reported in the modern literature. We present the case of a woman with epileptic seizures consisting of sustained fluctuation of perception of brightness. Bilateral pupillary hippus is the main semiologic feature.This autonomic phenomenon is selective for the pupils and does not involve other autonomic‐mediated responses. An ictal video illustrates this phenomenon. The epileptogenic region, determined by ictal scalp and intracranial electroencephalography (EEG), is localized in the right posterior parietooccipital areas. Pupillary reflexes can be overridden by cortical input; here authors review the literature and discus the physiologic mechanisms underlying this autonomic phenomenon. Fluctuation in perceptual brightness during epileptic seizures may have a basis in ictal pupillary hippus.