Independent component analysis reveals dynamic ictal BOLD responses in EEG-fMRI data from focal epilepsy patients

INTRODUCTION Seizures occur rarely during EEG-fMRI acquisitions of epilepsy patients, but can potentially offer a better estimation of the epileptogenic zone than interictal activity. Independent component analysis (ICA) is a data-driven method that imposes minimal constraints on the hemodynamic response function (HRF). In particular, the investigation of HRFs with clear peaks, but varying latency, may be used to differentiate the ictal focus from propagated activity. METHODS ICA was applied on ictal EEG-fMRI data from 15 patients. Components related to seizures were identified by fitting an HRF to the component time courses at the time of the ictal EEG events. HRFs with a clear peak were used to derive maps of significant BOLD responses and their associated peak delay. The results were then compared with those obtained from a general linear model (GLM) method. Concordance with the presumed epileptogenic focus was also assessed. RESULTS The ICA maps were significantly correlated with the GLM maps for each patient (Spearman's test, p<0.05). The ictal BOLD responses identified by ICA always included the presumed epileptogenic zone, but were also more widespread, accounting for 20.3% of the brain volume on average. The method provided a classification of the components as a function of peak delay. BOLD response clusters associated with early HRF peaks were concordant with the suspected epileptogenic focus, while subsequent HRF peaks may correspond to ictal propagation. CONCLUSION ICA applied to EEG-fMRI can detect areas of significant BOLD response to ictal events without having to predefine an HRF. By estimating the HRF peak time in each identified region, the method could also potentially provide a dynamic analysis of ictal BOLD responses, distinguishing onset from propagated activity.

[1]  J Gotman,et al.  Different structures involved during ictal and interictal epileptic activity in malformations of cortical development: an EEG-fMRI study. , 2008, Brain : a journal of neurology.

[2]  D. Collins,et al.  Automatic 3D Intersubject Registration of MR Volumetric Data in Standardized Talairach Space , 1994, Journal of computer assisted tomography.

[3]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[4]  F. Leijten,et al.  EEG-fMRI in the preoperative work-up for epilepsy surgery. , 2007, Brain : a journal of neurology.

[5]  A. Bernasconi,et al.  Surgical Resection for Intractable Epilepsy in “Double Cortex” Syndrome Yields Inadequate Results , 2001 .

[6]  J. Gotman,et al.  fMRI Activation in Continuous and Spike‐triggered EEG–fMRI Studies of Epileptic Spikes , 2003, Epilepsia.

[7]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[8]  L Tassi,et al.  Electroclinical, MRI and neuropathological study of 10 patients with nodular heterotopia, with surgical outcomes. , 2004, Brain : a journal of neurology.

[9]  Jean Gotman,et al.  Hemodynamic changes preceding the interictal EEG spike in patients with focal epilepsy investigated using simultaneous EEG-fMRI , 2009, NeuroImage.

[10]  Maromi Nei,et al.  Characteristics and clinical significance of subclinical seizures , 2008, Epilepsia.

[11]  Bruce Hermann,et al.  Ipsilateral and Contralateral MRI Volumetric Abnormalities in Chronic Unilateral Temporal Lobe Epilepsy and their Clinical Correlates , 2005, Epilepsia.

[12]  John S. Duncan,et al.  Independent component analysis of interictal fMRI in focal epilepsy: Comparison with general linear model-based EEG-correlated fMRI , 2007, NeuroImage.

[13]  Karl J. Friston,et al.  Movement‐Related effects in fMRI time‐series , 1996, Magnetic resonance in medicine.

[14]  G. Cascino Epilepsy and Brain Tumors: Implications for Treatment , 1990, Epilepsia.

[15]  Karl J. Friston,et al.  Assessing the significance of focal activations using their spatial extent , 1994, Human brain mapping.

[16]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited—Again , 1995, NeuroImage.

[17]  Jean Gotman,et al.  Variability of the hemodynamic response as a function of age and frequency of epileptic discharge in children with epilepsy , 2008, NeuroImage.

[18]  Frithjof Kruggel,et al.  Estimating the effective degrees of freedom in univariate multiple regression analysis , 2002, Medical Image Anal..

[19]  M. Walker,et al.  Noncanonical spike‐related BOLD responses in focal epilepsy , 2007, Human brain mapping.

[20]  L Tassi,et al.  Stereo-EEG of interictal and ictal electrical activity of a histologically proved heterotopic gray matter associated with partial epilepsy. , 1994, Electroencephalography and clinical neurophysiology.

[21]  Erkki Oja,et al.  Independent component analysis: algorithms and applications , 2000, Neural Networks.

[22]  J. Gotman,et al.  Quality of EEG in simultaneous EEG-fMRI for epilepsy , 2003, Clinical Neurophysiology.

[23]  N. Roberts,et al.  Voxel‐based morphometry of temporal lobe epilepsy: An introduction and review of the literature , 2008, Epilepsia.

[24]  J. Gotman,et al.  Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J Gotman,et al.  Widespread and intense BOLD changes during brief focal electrographic seizures , 2006, Neurology.

[26]  A. Kleinschmidt,et al.  Temporal lobe interictal epileptic discharges affect cerebral activity in “default mode” brain regions , 2006, Human brain mapping.

[27]  Stephen M. Smith,et al.  Probabilistic independent component analysis for functional magnetic resonance imaging , 2004, IEEE Transactions on Medical Imaging.

[28]  A. Friedman,et al.  Seizure onset from periventricular nodular heterotopias , 1998, Neurology.

[29]  L Tassi,et al.  A neuropathological, stereo-EEG, and MRI study of subcortical band heterotopia , 2003, Neurology.

[30]  Bruno Maraviglia,et al.  Ictal hemodynamic changes in late‐onset rasmussen encephalitis , 2006, Annals of neurology.

[31]  Afraim Salek-Haddadi,et al.  Simultaneous EEG-Correlated Ictal fMRI , 2002, NeuroImage.

[32]  Ludovico D'Incerti,et al.  Periventricular Nodular Heterotopia: Classification, Epileptic History, and Genesis of Epileptic Discharges , 2006, Epilepsia.

[33]  Oliver Granert,et al.  Changes in activity of striato–thalamo–cortical network precede generalized spike wave discharges , 2008, NeuroImage.

[34]  G. Glover Deconvolution of Impulse Response in Event-Related BOLD fMRI1 , 1999, NeuroImage.

[35]  G. Jackson,et al.  Functional MRI of the pre-ictal state. , 2005, Brain : a journal of neurology.

[36]  Amy Brooks-Kayal,et al.  Disorders of cortical development and epilepsy. , 2002, Archives of neurology.

[37]  Aapo Hyvärinen,et al.  Validating the independent components of neuroimaging time series via clustering and visualization , 2004, NeuroImage.

[38]  Alexander Hammers,et al.  Progressive neocortical damage in epilepsy , 2003, Annals of neurology.

[39]  Frederick Andermann,et al.  Intrinsic epileptogenicity of human dysplastic cortex as suggested by corticography and surgical results , 1995, Annals of neurology.

[40]  Robert Turner,et al.  A Method for Removing Imaging Artifact from Continuous EEG Recorded during Functional MRI , 2000, NeuroImage.

[41]  F. Morrell,et al.  Electrophysiology of heterotopic gray matter in the "double cortex" syndrome , 1992 .

[42]  I. R. Whittle,et al.  The Pathogenesis of Tumour Associated Epilepsy , 2000, Acta Neurochirurgica.

[43]  Yingli Lu,et al.  BOLD changes occur prior to epileptic spikes seen on scalp EEG , 2007, NeuroImage.

[44]  Karl J. Friston,et al.  Hemodynamic correlates of epileptiform discharges: An EEG-fMRI study of 63 patients with focal epilepsy , 2006, Brain Research.

[45]  J. Gotman,et al.  Independent component analysis as a model‐free approach for the detection of BOLD changes related to epileptic spikes: A simulation study , 2009, Human brain mapping.

[46]  Marco Carnì,et al.  EEG/fMRI Study of Ictal and Interictal Epileptic Activity: Methodological Issues and Future Perspectives in Clinical Practice , 2006, Epilepsia.

[47]  G. Srivastava,et al.  ICA-based procedures for removing ballistocardiogram artifacts from EEG data acquired in the MRI scanner , 2005, NeuroImage.

[48]  Jean Gotman,et al.  The BOLD Response to Interictal Epileptiform Discharges , 2002, NeuroImage.

[49]  Jean Gotman,et al.  The role of periventricular nodular heterotopia in epileptogenesis. , 2005, Brain : a journal of neurology.

[50]  Jean Gotman,et al.  EEG‐fMRI of focal epileptic spikes: Analysis with multiple haemodynamic functions and comparison with gadolinium‐enhanced MR angiograms , 2004, Human brain mapping.

[51]  Jane Neumann,et al.  Variability of the BOLD response over time: An examination of within-session differences , 2006, NeuroImage.

[52]  M. Sperling,et al.  Auras and subclinical seizures: Characteristics and prognostic significance , 1990, Annals of neurology.

[53]  S Makeig,et al.  Analysis of fMRI data by blind separation into independent spatial components , 1998, Human brain mapping.

[54]  M. D’Esposito,et al.  The Variability of Human, BOLD Hemodynamic Responses , 1998, NeuroImage.

[55]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[56]  H. Lüders,et al.  Presurgical evaluation of epilepsy. , 2001, Brain : a journal of neurology.

[57]  K O Lim,et al.  Cortical and Hippocampal Volume Deficits in Temporal Lobe Epilepsy , 1997, Epilepsia.

[58]  Mark D'Esposito,et al.  Variation of BOLD hemodynamic responses across subjects and brain regions and their effects on statistical analyses , 2004, NeuroImage.

[59]  L. Lemieux,et al.  Modelling large motion events in fMRI studies of patients with epilepsy. , 2007, Magnetic resonance imaging.

[60]  Richard A. Harshman,et al.  Noise Reduction in BOLD-Based fMRI Using Component Analysis , 2002, NeuroImage.

[61]  Xiaoping Hu,et al.  Ranking and averaging independent component analysis by reproducibility (RAICAR) , 2008, Human brain mapping.

[62]  Alan C. Evans,et al.  A general statistical analysis for fMRI data , 2000, NeuroImage.

[63]  Dirk Roos,et al.  Perilesional neurochemical changes in focal epilepsies , 1996, Acta Neuropathologica.

[64]  C. Daumas-Duport,et al.  Stereoelectroencephalography in focal cortical dysplasia: a 3D approach to delineating the dysplastic cortex. , 2000, Brain : a journal of neurology.

[65]  David F Abbott,et al.  Cortical/subcortical BOLD changes associated with epileptic discharges , 2005, Neurology.

[66]  Catie Chang,et al.  Mapping and correction of vascular hemodynamic latency in the BOLD signal , 2008, NeuroImage.

[67]  J. Gotman,et al.  Cortical and thalamic fMRI responses in partial epilepsy with focal and bilateral synchronous spikes , 2006, Clinical Neurophysiology.