Impaired Resting-State Functional Integrations within Default Mode Network of Generalized Tonic-Clonic Seizures Epilepsy

Generalized tonic-clonic seizures (GTCS) are characterized by unresponsiveness and convulsions, which cause complete loss of consciousness. Many recent studies have found that the ictal alterations in brain activity of the GTCS epilepsy patients are focally involved in some brain regions, including thalamus, upper brainstem, medial prefrontal cortex, posterior midbrain regions, and lateral parietal cortex. Notably, many of these affected brain regions are the same and overlap considerably with the components of the so-called default mode network (DMN). Here, we hypothesize that the brain activity of the DMN of the GTCS epilepsy patients are different from normal controls, even in the resting state. To test this hypothesis, we compared the DMN of the GTCS epilepsy patients and the controls using the resting state functional magnetic resonance imaging. Thirteen brain areas in the DMN were extracted, and a complete undirected weighted graph was used to model the DMN for each participant. When directly comparing the edges of the graph, we found significant decreased functional connectivities within the DMN of the GTCS epilepsy patients comparing to the controls. As for the nodes of the graph, we found that the degree of some brain areas within the DMN was significantly reduced in the GTCS epilepsy patients, including the anterior medial prefrontal cortex, the bilateral superior frontal cortex, and the posterior cingulate cortex. Then we investigated into possible mechanisms of how GTCS epilepsy could cause the reduction of the functional integrations of DMN. We suggested the damaged functional integrations of the DMN in the GTCS epilepsy patients even during the resting state, which could help to understand the neural correlations of the impaired consciousness of GTCS epilepsy patients.

[1]  A. Braun,et al.  Decoupling of the brain's default mode network during deep sleep , 2009, Proceedings of the National Academy of Sciences.

[2]  A. Kleinschmidt,et al.  Linking Generalized Spike‐and‐Wave Discharges and Resting State Brain Activity by Using EEG/fMRI in a Patient with Absence Seizures , 2006, Epilepsia.

[3]  Alexa M. Morcom,et al.  Does the brain have a baseline? Why we should be resisting a rest , 2007, NeuroImage.

[4]  Karl J. Friston,et al.  EEG–fMRI of idiopathic and secondarily generalized epilepsies , 2006, NeuroImage.

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

[6]  Joshua E. Motelow,et al.  Cortical and subcortical networks in human secondarily generalized tonic-clonic seizures. , 2009, Brain : a journal of neurology.

[7]  M. Boly,et al.  Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. , 2010, Brain : a journal of neurology.

[8]  C. Elger,et al.  New Antiepileptic Drugs in Epileptology , 1998, Neuropsychobiology.

[9]  M. Corbetta,et al.  Common Blood Flow Changes across Visual Tasks: II. Decreases in Cerebral Cortex , 1997, Journal of Cognitive Neuroscience.

[10]  Christian E Elger,et al.  Chronic epilepsy and cognition , 2004, The Lancet Neurology.

[11]  M. Mintun,et al.  Brain work and brain imaging. , 2006, Annual review of neuroscience.

[12]  B. Mazoyer,et al.  Cortical networks for working memory and executive functions sustain the conscious resting state in man , 2001, Brain Research Bulletin.

[13]  S. Petersen,et al.  Development of distinct control networks through segregation and integration , 2007, Proceedings of the National Academy of Sciences.

[14]  B. Liu,et al.  Prefrontal-Related Functional Connectivities within the Default Network Are Modulated by COMT val158met in Healthy Young Adults , 2010, The Journal of Neuroscience.

[15]  M. Raichle,et al.  Cortical network functional connectivity in the descent to sleep , 2009, Proceedings of the National Academy of Sciences.

[16]  A. Cavanna,et al.  Brain mechanisms of altered conscious states during epileptic seizures , 2009, Nature Reviews Neurology.

[17]  Karl J. Friston,et al.  Functional Connectivity: The Principal-Component Analysis of Large (PET) Data Sets , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Abraham Z. Snyder,et al.  A default mode of brain function: A brief history of an evolving idea , 2007, NeuroImage.

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

[21]  Cheng Luo,et al.  EEG–fMRI study on the interictal and ictal generalized spike-wave discharges in patients with childhood absence epilepsy , 2009, Epilepsy Research.

[22]  Biyu J. He,et al.  Breakdown of Functional Connectivity in Frontoparietal Networks Underlies Behavioral Deficits in Spatial Neglect , 2007, Neuron.

[23]  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.

[24]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[25]  Tianzi Jiang,et al.  Default network and intelligence difference , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[26]  Justin L. Vincent,et al.  Intrinsic functional architecture in the anaesthetized monkey brain , 2007, Nature.

[27]  M. Raichle,et al.  Disease and the brain's dark energy , 2010, Nature Reviews Neurology.

[28]  S. Petersen,et al.  The maturing architecture of the brain's default network , 2008, Proceedings of the National Academy of Sciences.

[29]  Randy L. Buckner,et al.  Unrest at rest: Default activity and spontaneous network correlations , 2007, NeuroImage.

[30]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[31]  Huafu Chen,et al.  Altered spontaneous neuronal activity of the default-mode network in mesial temporal lobe epilepsy , 2010, Brain Research.

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

[33]  G. Jackson,et al.  Functional connectivity networks are disrupted in left temporal lobe epilepsy , 2006, Annals of neurology.

[34]  M. Fukunaga,et al.  Low frequency BOLD fluctuations during resting wakefulness and light sleep: A simultaneous EEG‐fMRI study , 2008, Human brain mapping.

[35]  Justin L. Vincent,et al.  Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Yuan Zhou,et al.  The relationship within and between the extrinsic and intrinsic systems indicated by resting state correlational patterns of sensory cortices , 2007, NeuroImage.

[37]  Justin L. Vincent,et al.  Distinct brain networks for adaptive and stable task control in humans , 2007, Proceedings of the National Academy of Sciences.