Are high frequency oscillations associated with altered network topology in partial epilepsy?

Neurophysiological studies have reported functional network alterations in epilepsy, most consistently in the theta frequency band. Highly interconnected brain regions (so-called 'hubs') seem to be important in these epileptic networks. High frequency oscillations (HFOs) in intracranial EEG recordings are recently discovered biomarkers that can identify the epileptogenic area and are thought to result from altered neuronal interactions. We studied whether the epileptogenic zone (identified by HFOs and seizure onset zone) is associated with pathological hubs. Bilateral depth electrode recordings from the hippocampus and amygdala were available from twelve patients suspected of temporal lobe epilepsy. HFOs, classified as ripples (80-250 Hz) and fast ripples (250-500 Hz), and epileptiform spikes were marked for all patients in a five-minute epoch of slow-wave sleep. For each channel, we computed hub-measures from a period without epileptiform spikes and found that the epileptogenic zone was associated with a decreased hub-value in the theta frequency band. The amount of HFOs, especially fast ripples, was negatively correlated with the hub-value per channel. Results from post-hoc analyses of other frequency bands, particularly the broad- and gamma frequency band, pointed in the same direction as the results for the theta frequency band. These findings suggest a pathological functional 'isolation' of the epileptogenic zone in the interictal state.

[1]  Stefan Burr,et al.  The Mathematics of networks , 1982 .

[2]  M. Kramer,et al.  Epilepsy as a Disorder of Cortical Network Organization , 2012, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[3]  Luis Concha,et al.  Extratemporal White Matter Abnormalities in Mesial Temporal Lobe Epilepsy Demonstrated with Diffusion Tensor Imaging , 2006, Epilepsia.

[4]  C. Stam,et al.  Improved Diagnosis in Children with Partial Epilepsy Using a Multivariable Prediction Model Based on EEG Network Characteristics , 2013, PloS one.

[5]  Cornelis J. Stam,et al.  Cognitive Dysfunction in Early Multiple Sclerosis: Altered Centrality Derived from Resting-State Functional Connectivity Using Magneto-Encephalography , 2012, PloS one.

[6]  Charles L. Wilson,et al.  Local Generation of Fast Ripples in Epileptic Brain , 2002, The Journal of Neuroscience.

[7]  Mark P Richardson,et al.  Large scale brain models of epilepsy: dynamics meets connectomics , 2012, Journal of Neurology, Neurosurgery & Psychiatry.

[8]  P. Hofman,et al.  Loss of network efficiency associated with cognitive decline in chronic epilepsy , 2011, Neurology.

[9]  Jerome Engel,et al.  Outcome with respect to epileptic seizures. , 1993 .

[10]  Charles L. Wilson,et al.  Hippocampal and Entorhinal Cortex High‐Frequency Oscillations (100–500 Hz) in Human Epileptic Brain and in Kainic Acid‐Treated Rats with Chronic Seizures , 1999, Epilepsia.

[11]  Pierre LeVan,et al.  High‐Frequency Intracerebral EEG Activity (100–500 Hz) Following Interictal Spikes , 2006, Epilepsia.

[12]  John M Stern,et al.  Connectomics and epilepsy. , 2013, Current opinion in neurology.

[13]  Uwe Heinemann,et al.  Basic mechanisms of partial epilepsies , 2004, Current opinion in neurology.

[14]  Linda Douw,et al.  MEG Network Differences between Low- and High-Grade Glioma Related to Epilepsy and Cognition , 2012, PloS one.

[15]  Ayako Ochi,et al.  Focal resection of fast ripples on extraoperative intracranial EEG improves seizure outcome in pediatric epilepsy , 2011, Epilepsia.

[16]  J. Régis,et al.  Enhanced EEG functional connectivity in mesial temporal lobe epilepsy , 2008, Epilepsy Research.

[17]  Ayako Ochi,et al.  Dynamic Changes of Ictal High‐Frequency Oscillations in Neocortical Epilepsy: Using Multiple Band Frequency Analysis , 2007, Epilepsia.

[18]  A. Bernasconi,et al.  Progression in temporal lobe epilepsy , 2005, Neurology.

[19]  P J Allen,et al.  Very high-frequency rhythmic activity during SEEG suppression in frontal lobe epilepsy. , 1991, Electroencephalography and clinical neurophysiology.

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

[21]  G. Buzsáki,et al.  Neuronal Oscillations in Cortical Networks , 2004, Science.

[22]  Huafu Chen,et al.  Altered Functional Connectivity and Small-World in Mesial Temporal Lobe Epilepsy , 2010, PloS one.

[23]  J. Pastor,et al.  Synchronization Clusters of Interictal Activity in the Lateral Temporal Cortex of Epileptic Patients: Intraoperative Electrocorticographic Analysis , 2008, Epilepsia.

[24]  Itzhak Fried,et al.  Increased Fast ripple to ripple Ratios Correlate with Reduced Hippocampal Volumes and Neuron Loss in Temporal Lobe Epilepsy Patients , 2007, Epilepsia.

[25]  J. Gotman,et al.  Patterns of altered functional connectivity in mesial temporal lobe epilepsy , 2012, Epilepsia.

[26]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[27]  Jean Gotman,et al.  Erratum: High-frequency intracerebral EEG activity (100-500 Hz) following interictal spikes (Epilepsia (2006) 47, (1465-1476)) , 2006 .

[28]  J. Gotman,et al.  High frequency oscillations in intracranial EEGs mark epileptogenicity rather than lesion type. , 2009, Brain : a journal of neurology.

[29]  Shuang Wang,et al.  Ripple classification helps to localize the seizure‐onset zone in neocortical epilepsy , 2013, Epilepsia.

[30]  J. Gotman,et al.  High-frequency oscillations during human focal seizures. , 2006, Brain : a journal of neurology.

[31]  Helen J. Cross,et al.  A Possible Role for Gap Junctions in Generation of Very Fast EEG Oscillations Preceding the Onset of, and Perhaps Initiating, Seizures , 2001, Epilepsia.

[32]  Fiona E. N. LeBeau,et al.  A Possible Role for Gap Junctions in Generation of Very Fast EEG Oscillations Preceding the Onset of, and Perhaps Initiating, Seizures , 2001 .

[33]  C. Stam,et al.  The organization of physiological brain networks , 2012, Clinical Neurophysiology.

[34]  P. Bonacich Power and Centrality: A Family of Measures , 1987, American Journal of Sociology.

[35]  D. Velis,et al.  Long-Term Effects of Temporal Lobe Epilepsy on Local Neural Networks: A Graph Theoretical Analysis of Corticography Recordings , 2009, PloS one.

[36]  Charles L. Wilson,et al.  High‐frequency oscillations in human brain , 1999, Hippocampus.

[37]  Massimo Avoli,et al.  Ripple activity in the dentate gyrus of dishinibited hippocampus‐entorhinal cortex slices , 2005, Journal of neuroscience research.

[38]  Cornelis J Stam,et al.  Graph theoretical analysis of complex networks in the brain , 2007, Nonlinear biomedical physics.

[39]  Jerome Engel,et al.  Introduction to temporal lobe epilepsy , 1996, Epilepsy Research.

[40]  Fabrice Wendling,et al.  Mechanisms of physiological and epileptic HFO generation , 2012, Progress in Neurobiology.

[41]  Bin He,et al.  Graph analysis of epileptogenic networks in human partial epilepsy , 2011, Epilepsia.

[42]  R. Turner,et al.  Eigenvector Centrality Mapping for Analyzing Connectivity Patterns in fMRI Data of the Human Brain , 2010, PloS one.

[43]  G. Mathern,et al.  Removing interictal fast ripples on electrocorticography linked with seizure freedom in children , 2010, Neurology.

[44]  Kevin J. Staley,et al.  Mechanisms of Fast Ripples in the Hippocampus , 2004, The Journal of Neuroscience.

[45]  Asla Pitkänen,et al.  MRI volumetry and T2 relaxometry of the amygdala in newly diagnosed and chronic temporal lobe epilepsy , 1997, Epilepsy Research.

[46]  C J Stam,et al.  Characterization of anatomical and functional connectivity in the brain: a complex networks perspective. , 2010, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[47]  Michel A. Picardo,et al.  GABAergic Hub Neurons Orchestrate Synchrony in Developing Hippocampal Networks , 2009, Science.

[48]  Eishi Asano,et al.  Spontaneous and visually driven high‐frequency oscillations in the occipital cortex: Intracranial recording in epileptic patients , 2012, Human brain mapping.

[49]  K. Lehnertz,et al.  State dependent properties of epileptic brain networks: Comparative graph–theoretical analyses of simultaneously recorded EEG and MEG , 2010, Clinical Neurophysiology.

[50]  B. Litt,et al.  High-frequency oscillations and seizure generation in neocortical epilepsy. , 2004, Brain : a journal of neurology.

[51]  C. Stam,et al.  ‘Functional Connectivity’ Is a Sensitive Predictor of Epilepsy Diagnosis after the First Seizure , 2010, PloS one.

[52]  Alejandro F. Bujan,et al.  High-Frequency Network Activity, Global Increase in Neuronal Activity, and Synchrony Expansion Precede Epileptic Seizures In Vitro , 2010, The Journal of Neuroscience.

[53]  Hajime Miyata,et al.  Defining Clinico‐Neuropathological Subtypes of Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis , 2012, Brain pathology.

[54]  N. Voets,et al.  Structural substrates for resting network disruption in temporal lobe epilepsy. , 2012, Brain : a journal of neurology.

[55]  P. Chauvel,et al.  Decreased basal fMRI functional connectivity in epileptogenic networks and contralateral compensatory mechanisms , 2009, Human brain mapping.

[56]  Piet Van Mieghem,et al.  Disruption of Functional Brain Networks in Alzheimer's Disease: What Can We Learn from Graph Spectral Analysis of Resting-State Magnetoencephalography? , 2012, Brain Connect..

[57]  C. Stam,et al.  Small-world networks and epilepsy: Graph theoretical analysis of intracerebrally recorded mesial temporal lobe seizures , 2007, Clinical Neurophysiology.

[58]  Paul J. Laurienti,et al.  A New Measure of Centrality for Brain Networks , 2010, PloS one.

[59]  O. Sporns,et al.  Network centrality in the human functional connectome. , 2012, Cerebral cortex.

[60]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[61]  E. Whitham,et al.  Scalp electrical recording during paralysis: Quantitative evidence that EEG frequencies above 20Hz are contaminated by EMG , 2007, Clinical Neurophysiology.

[62]  J. Gotman,et al.  Effect of sleep stage on interictal high‐frequency oscillations recorded from depth macroelectrodes in patients with focal epilepsy , 2009, Epilepsia.

[63]  M. Weiner,et al.  Voxel‐based Optimized Morphometry (VBM) of Gray and White Matter in Temporal Lobe Epilepsy (TLE) with and without Mesial Temporal Sclerosis , 2006, Epilepsia.

[64]  I. Módy,et al.  High-frequency oscillations : What is normal and what is not ? , 2008 .

[65]  H. Berendse,et al.  The application of graph theoretical analysis to complex networks in the brain , 2007, Clinical Neurophysiology.

[66]  J. Gotman,et al.  High‐frequency electroencephalographic oscillations correlate with outcome of epilepsy surgery , 2010, Annals of neurology.

[67]  Mark R. Bower,et al.  Synchrony in normal and focal epileptic brain: the seizure onset zone is functionally disconnected. , 2010, Journal of neurophysiology.

[68]  Linda Douw,et al.  Epilepsy is related to theta band brain connectivity and network topology in brain tumor patients , 2010, BMC Neuroscience.

[69]  Eileen Luders,et al.  Distinct regional atrophy in the corpus callosum of patients with temporal lobe epilepsy. , 2007, Brain : a journal of neurology.

[70]  Guglielmo Foffani,et al.  Emergent Dynamics of Fast Ripples in the Epileptic Hippocampus , 2010, The Journal of Neuroscience.

[71]  C. Stam,et al.  Phase lag index: Assessment of functional connectivity from multi channel EEG and MEG with diminished bias from common sources , 2007, Human brain mapping.

[72]  R. Morgan,et al.  Nonrandom connectivity of the epileptic dentate gyrus predicts a major role for neuronal hubs in seizures , 2008, Proceedings of the National Academy of Sciences.

[73]  Jeffery A. Hall,et al.  Interictal high‐frequency oscillations (80–500 Hz) are an indicator of seizure onset areas independent of spikes in the human epileptic brain , 2008, Epilepsia.

[74]  Yu-Feng Zang,et al.  Alterations in regional homogeneity of baseline brain activity in pediatric temporal lobe epilepsy , 2011, Brain Research.