Characterization of Functional and Structural Integrity in Experimental Focal Epilepsy: Reduced Network Efficiency Coincides with White Matter Changes

Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
PLoS ONE (Impact Factor: 3.53). 07/2012; 7(7):e39078. DOI: 10.1371/journal.pone.0039078
Source: PubMed

ABSTRACT Although focal epilepsies are increasingly recognized to affect multiple and remote neural systems, the underlying spatiotemporal pattern and the relationships between recurrent spontaneous seizures, global functional connectivity, and structural integrity remain largely unknown.
Here we utilized serial resting-state functional MRI, graph-theoretical analysis of complex brain networks and diffusion tensor imaging to characterize the evolution of global network topology, functional connectivity and structural changes in the interictal brain in relation to focal epilepsy in a rat model. Epileptic networks exhibited a more regular functional topology than controls, indicated by a significant increase in shortest path length and clustering coefficient. Interhemispheric functional connectivity in epileptic brains decreased, while intrahemispheric functional connectivity increased. Widespread reductions of fractional anisotropy were found in white matter regions not restricted to the vicinity of the epileptic focus, including the corpus callosum.
Our longitudinal study on the pathogenesis of network dynamics in epileptic brains reveals that, despite the locality of the epileptogenic area, epileptic brains differ in their global network topology, connectivity and structural integrity from healthy brains.

Download full-text


Available from: Rick M Dijkhuizen, Aug 10, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: The ultimate goal of epilepsy surgery in young children is to stop seizures, interrupt the downhill course of the epileptic encephalopathy, and improve developmental capacities. Postoperative outcome after childhood epilepsy surgery should therefore not only be expressed in terms of seizure freedom, cognitive outcome is an equally important outcome measure. Insight in the mutually dependent variables that can determine pre and postoperative cognitive developmental abilities will improve prediction of outcome and presurgical counseling of parents. The purpose of this review is to discuss the literature regarding cognitive outcome and the predictors of postoperative cognitive functioning after epilepsy surgery in children, particularly those with "catastrophic" epilepsy. There are only few studies in which the relation between possible determinants and cognitive outcome or change was statistically tested in a multivariable manner. Duration of epilepsy, presurgical Developmental Quotient (DQ) or Intelligence Quotient (IQ), and postoperative seizure freedom were the only factors reported in different studies to be independently related to eventual cognitive outcome after epilepsy surgery. Underlying etiology, gender, age at surgery, presurgical DQ/IQ, postoperative seizure freedom, cessation of antiepileptic medication, and follow-up interval have all been described in different surgical cohorts to be independently related to a postoperative change of IQ or DQ scores. To appreciate how each of the pre-epileptic, presurgical, and postoperative variables may independently influence eventual cognitive outcome and postoperative cognitive improvement, we need multicenter studies with large homogenous surgical populations, using standardized tests and multivariable analyses.
    Brain & development 02/2013; 35(8). DOI:10.1016/j.braindev.2013.01.011 · 1.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tremendous advances have occurred in recent years in elucidating basic mechanisms of epilepsy at the level of ion channels and neurotransmitters. Epilepsy, however, is ultimately a disease of functionally and/or structurally aberrant connections between neurons and groups of neurons at the systems level. Recent advances in neuroimaging and electrophysiology now make it possible to investigate structural and functional connectivity of the entire brain, and these techniques are currently being used to investigate diseases that manifest as global disturbances of brain function. Epilepsy is such a disease, and our understanding of the mechanisms underlying the development of epilepsy and the generation of epileptic seizures will undoubtedly benefit from research utilizing these connectomic approaches. MRI using diffusion tensor imaging provides structural information, whereas functional MRI and electroencephalography provide functional information about connectivity at the whole brain level. Optogenetics, tracers, electrophysiological approaches, and calcium imaging provide connectivity information at the level of local circuits. These approaches are revealing important neuronal network disturbances underlying epileptic abnormalities. An understanding of the fundamental mechanisms underlying the development of epilepsy and the generation of epileptic seizures will require delineation of the aberrant functional and structural connections of the whole brain. The field of connectomics now provides approaches to accomplish this.
    Current opinion in neurology 04/2013; 26(2):186-94. DOI:10.1097/WCO.0b013e32835ee5b8 · 5.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Graph theoretical analysis of functional connectivity data has demonstrated a small-world topology of brain networks. There is increasing evidence that the topology of brain networks is changed in epilepsy. Here we investigated the basal properties of epileptogenic networks by applying graph analysis to intracerebral EEG recordings of patients presenting with drug-resistant partial epilepsies during the interictal period. Interictal EEG activity was recorded in mesial temporal lobe of 11 patients with mesial temporal lobe epilepsy (MTLE group) and compared with a "control" group of 8 patients having neocortical epilepsies (non MTLE group) in whom depth-EEG recordings eventually showed an ictal onset outside the MTL structures. Synchronization likelihood (SL) was calculated between selected intracerebral electrodes contacts to obtain SL-weighted graphs. Mean normalized clustering index, average path length and small world index S were calculated to characterize network organization. Broadband SL values were higher in the MTLE group. Although a small-world pattern was found in the two groups, normalized clustering index and to a lesser extend average path length were higher in the MTLE group. We demonstrated a trend toward a more regular (less random) configuration of interictal epileptogenic networks. In addition S index was found to correlate with epilepsy duration. These topological alterations might be a surrogate marker of human focal epilepsy and disclose some changes over time.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 06/2013; 124(12). DOI:10.1016/j.clinph.2013.06.003 · 2.98 Impact Factor
Show more