Cognitive and behavioral comorbidities in Rolandic epilepsy and their relation with default mode network's functional connectivity and organization

OBJECTIVE Rolandic epilepsy (RE) is characterized by typical interictal-electroencephalogram (EEG) patterns mainly localized in centrotemporal and parietooccipital areas. An aberrant intrinsic organization of the default mode network (DMN) due to repeated disturbances from spike-generating areas may be able to account for specific cognitive deficits and behavioral problems in RE. The aim of the present study was to investigate cognitive development (CD) and socioemotional development (SED) in patients with RE during active disease in relation to DMN connectivity and network topology. METHODS In 10 children with RE and active EEG, CD was assessed using the Wechsler Intelligence Scale for Children-IV (WISC-IV); SED was assessed using the Fünf-Faktoren-Fragebogen für Kinder (FFFK), a Big-Five inventory for the assessment of personality traits in children. Functional connectivity (FC) in the DMN was determined from a 15-minute resting state functional magnetic resonance imaging (fMRI), and network properties were calculated using standard graph-theoretical measures. RESULTS More severe deficits of verbal abilities tended to be associated with an earlier age at epilepsy onset, but were not directly related to the number of seizures and disease duration. Nonetheless, at the network level, disease duration was associated with alterations of the efficiency and centrality of parietal network nodes and midline structures. Particularly, centrality of the left inferior parietal lobe (IPL) was found to be linked with CD. Reduced centrality of the left IPL and alterations supporting a rather segregated processing within DMN's subsystems was associated with a more favorable CD. A more complicated SED was associated with high seizure frequency and long disease duration, and revealed links with a less favorable CD. SIGNIFICANCE An impaired CD and - because of their interrelation - SED might be mediated by a common pathomechanism reflected in an aberrant organization, and thus, a potential functional deficit of the DMN. A functional segregation of (left) parietal network nodes from the DMN and a rather segregated processing mode within the DMN might have positive implications/protective value for CD in patients with RE.

[1]  Peter Boesiger,et al.  Reduced negative BOLD responses in the default-mode network and increased self-focus in depression , 2011, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[2]  Mark W. Woolrich,et al.  Resting-state fMRI in the Human Connectome Project , 2013, NeuroImage.

[3]  Maja Steinlin,et al.  Cognitive impairment and cortical reorganization in children with benign epilepsy with centrotemporal spikes , 2013, Epilepsia.

[4]  D. Wechsler.  Wechsler Intelligence Scale for Children , 2020, Definitions.

[5]  D. Riva,et al.  Intellectual and language findings and their relationship to EEG characteristics in benign childhood epilepsy with centrotemporal spikes , 2007, Epilepsy & Behavior.

[6]  A. Leal,et al.  Origin and dynamics of epileptic activity in a symptomatic case of Panayiotopoulos syndrome: Correlation with clinical manifestations , 2013, Clinical Neurophysiology.

[7]  Andreas Schulze-Bonhage,et al.  Fast fMRI provides high statistical power in the analysis of epileptic networks , 2014, NeuroImage.

[8]  Walter H. Backes,et al.  Early onset of cortical thinning in children with rolandic epilepsy☆ , 2013, NeuroImage: Clinical.

[9]  J. Jeon,et al.  The impact of an exercise therapy on psychosocial health of children with benign epilepsy: A pilot study , 2014, Epilepsy & Behavior.

[10]  R. Caraballo.  Nonpharmacologic treatments of Dravet syndrome: Focus on the ketogenic diet , 2011, Epilepsia.

[11]  A. Byars,et al.  Behavior problems in children at time of first recognized seizure and changes over the following 3years , 2011, Epilepsy & Behavior.

[12]  Dinggang Shen,et al.  Cerebral Cortex doi:10.1093/cercor/bhs043 Cerebral Cortex Advance Access published February 24, 2012 The Synchronization within and Interaction between the Default and Dorsal Attention Networks in Early Infancy , 2022 .

[13]  G. Gobbi,et al.  Neuropsychological development in children belonging to BECTS spectrum: Long-term effect of epileptiform activity , 2013, Epilepsy & Behavior.

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

[15]  B. Aldenkamp,et al.  Cognitive effects of interictal epileptiform discharges in children. , 2012, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[16]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[17]  Kristina M. Visscher,et al.  The neural bases of momentary lapses in attention , 2006, Nature Neuroscience.

[18]  Maxim Zaitsev,et al.  Fast Undersampled Functional Magnetic Resonance Imaging Using Nonlinear Regularized Parallel Image Reconstruction , 2011, PloS one.

[19]  G H Glover,et al.  Image‐based method for retrospective correction of physiological motion effects in fMRI: RETROICOR , 2000, Magnetic resonance in medicine.

[20]  C. Marescaux,et al.  EEG criteria predictive of complicated evolution in idiopathic rolandic epilepsy , 2001, Neurology.

[21]  Yong He,et al.  BrainNet Viewer: A Network Visualization Tool for Human Brain Connectomics , 2013, PloS one.

[22]  M. Mintun,et al.  The default mode network and self-referential processes in depression , 2009, Proceedings of the National Academy of Sciences.

[23]  F. Petermann,et al.  Cognitive deficits in children with benign rolandic epilepsy of childhood or rolandic discharges: A study of children between 4 and 7 years of age with and without seizures compared with healthy controls , 2009, Epilepsy & Behavior.

[24]  Jürgen Hennig,et al.  Single shot whole brain imaging using spherical stack of spirals trajectories , 2013, NeuroImage.

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

[26]  S. Debener,et al.  Default-mode brain dysfunction in mental disorders: A systematic review , 2009, Neuroscience & Biobehavioral Reviews.

[27]  J. Arends,et al.  The cognitive effects of interictal epileptiform EEG discharges and short nonconvulsive epileptic seizures , 2012, Epilepsia.

[28]  T. Valiante,et al.  Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy , 2013, Epilepsia.

[29]  P. Berquin,et al.  Clinical evaluation of attentional processes in children with benign childhood epilepsy with centrotemporal spikes (BCECTS). , 2007, Epileptic disorders : international epilepsy journal with videotape.

[30]  Rūta Samaitienė,et al.  Behavioral problems in children with benign childhood epilepsy with centrotemporal spikes treated and untreated with antiepileptic drugs. , 2012, Medicina.

[31]  J L McGaugh,et al.  Time-Dependent Processes in Memory Storage , 1966, Science.

[32]  Peter Wolf,et al.  The system epilepsies: A pathophysiological hypothesis , 2012, Epilepsia.

[33]  M. Yum,et al.  Determinants of intelligence in childhood-onset epilepsy: A single-center study , 2013, Epilepsy & Behavior.

[34]  Torsten Baldeweg,et al.  Language deficits and altered hemispheric lateralization in young people in remission from BECTS , 2011, Epilepsia.

[35]  N. Birbaumer,et al.  Benign Partial Epilepsy in Childhood: Selective Cognitive Deficits Are Related to the Location of Focal Spikes Determined by Combined EEG/MEG , 2005, Epilepsia.

[36]  Klaus Lehnertz,et al.  Automated detection of a preseizure state based on a decrease in synchronization in intracranial electroencephalogram recordings from epilepsy patients. , 2003, Physical review. E, Statistical, nonlinear, and soft matter physics.

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

[38]  Michael Koutroumanidis,et al.  Benign childhood focal epilepsies: assessment of established and newly recognized syndromes. , 2008, Brain : a journal of neurology.

[39]  M. Greicius,et al.  Resting-state functional connectivity reflects structural connectivity in the default mode network. , 2009, Cerebral cortex.

[40]  R. Borgatti,et al.  Academic performance in children with rolandic epilepsy , 2008 .

[41]  John R. Williams.  The Declaration of Helsinki and public health. , 2008, Bulletin of the World Health Organization.

[42]  J. Martinerie,et al.  Toward a Neurodynamical Understanding of Ictogenesis , 2003, Epilepsia.

[43]  Andreas Schulze-Bonhage,et al.  Negative BOLD in default-mode structures measured with EEG-MREG is larger in temporal than extra-temporal epileptic spikes , 2014, Front. Neurosci..

[44]  Walter H. Backes,et al.  Aberrant functional connectivity between motor and language networks in rolandic epilepsy , 2013, Epilepsy Research.

[45]  G. Gobbi,et al.  The Spectrum of Idiopathic Rolandic Epilepsy Syndromes and Idiopathic Occipital Epilepsies: From the Benign to the Disabling , 2006, Epilepsia.

[46]  K. Specht,et al.  Default mode network alterations during language task performance in children with benign epilepsy with centrotemporal spikes (BECTS) , 2014, Epilepsy & Behavior.

[47]  L. Nobili,et al.  Neuropsychological disorders related to interictal epileptic discharges during sleep in benign epilepsy of childhood with centrotemporal or Rolandic spikes. , 2001, Developmental medicine and child neurology.

[48]  M. Rugg,et al.  When more means less neural activity related to unsuccessful memory encoding , 2001, Current Biology.

[49]  E. Wirrell,et al.  Deterioration in Cognitive Function in Children With Benign Epilepsy of Childhood With Central Temporal Spikes Treated With Sulthiame , 2008, Journal of child neurology.

[50]  Q. Gong,et al.  Real-time effects of centrotemporal spikes on cognition in rolandic epilepsy , 2016, Neurology.

[51]  Peter Fransson,et al.  Resting-state networks in the infant brain , 2007, Proceedings of the National Academy of Sciences.

[52]  R. Guerrini,et al.  Benign childhood focal epilepsies , 2012, Epilepsia.

[53]  O. Gonen,et al.  Neuropsychological aspects of benign childhood epilepsy with centrotemporal spikes , 2010, Seizure.

[54]  Alan C. Evans,et al.  A General Statistical Analysis for fMRI Data , 2000, NeuroImage.