Epilepsy Connectome Project

Study Overview

The Epilepsy Connectome Project (ECP) will focus on gaining a better understanding of why some patients respond well to anticonvulsant therapy, whereas others develop controlled seizures and progressive brain dysfunction.  The ECP will use imaging tools for quantitatively characterizing the structural and functional connections between brain regions to aid in treating refractory epilepsy.  Temporal lobe epilepsy (TLE), the most common form of epilepsy in adults and the largest group among those with medically refractory seizures, will be a key focus of the study.  The study will explore a number of issues relating to connectivity abnormalities, such as:  the impact of recurring seizures over many years in TLE, the correlation to cognitive and psychosocial dysfunction observed in people with TLE, that the severity predicts the risk of subsequent decline in cognitive and psychosocial function, and that the severity predicts the risk of developing medically refractory seizures.

Project Timespan: Sept. 1, 2015 - Aug. 31, 2019


Jeff Binder

Jeff Binder, M.D. - MCW Principal Investigator

Contact: Email

Beth Meyerand

Beth Meyerand, Ph.D. - UWisc Principal Investigator

Contact: Email

Study Protocol Overview

Data being collected

  • Standard HCP demographics, along with demographic surveys, medical and seizure history. 
  • Imaging:
  • MR data collection at both sites will be conducted on a GE MR750 3T scanner and using imaging modalities including diffusion-weighted MR imaging of structural, functional (resting state and task) of dynamic network interactions.
  • Magnetoencephalography (MEG).
  • Clinical: Neuropsychological testing, blood work (genetics).
  • Behavioral: In addition to HCP fMRI tasks, language lateralization and Semantic Memory fMRI tasks, will be added as they are critical to assessing Epilepsy patients.  The HCP LifeSpan gambling task will not be performed.

Cohort Description

A total of 340 participants ages 18-50 will be enrolled in the study, consisting of 140 healthy controls, and 200 participants with idiopathic TLE. 

Data Release Plans

  • The first data release includes 100 participants.
  • The second data release includes 200 participants.
  • The third data release includes 340 participants.


Epilepsy, refractory, Temporal lobe epilepsy (TLE), idiopathic TLE, magnetoencephalography


  • Age-Related Changes in BOLD Activation Pattern in Phonemic Fluency Paradigm: An Investigation of Activation, Functional Connectivity and Psychophysiological Interactions.

    Christian La, Camille Garcia-Ramos, Veena A Nair, Timothy B Meier, Dorothy Farrar-Edwards, Rasmus Birn, Mary E Meyerand, Vivek Prabhakaran
    Show Summary

    Healthy aging is associated with decline of cognitive functions. However, even before those declines become noticeable, the neural architecture underlying those mechanisms has undergone considerable restructuring and reorganization. During performance of a cognitive task, not only have the task-relevant networks demonstrated reorganization with aging, which occurs primarily by recruitment of additional areas to preserve performance, but the task-irrelevant network of the "default-mode" network (DMN), which is normally deactivated during task performance, has also consistently shown reduction of this deactivation with aging. Here, we revisited those age-related changes in task-relevant (i.e., language system) and task-irrelevant (i.e., DMN) systems with a language production paradigm in terms of task-induced activation/deactivation, functional connectivity, and context-dependent correlations between the two systems. Our task fMRI data demonstrated a late increase in cortical recruitment in terms of extent of activation, only observable in our older healthy adult group, when compared to the younger healthy adult group, with recruitment of the contralateral hemisphere, but also other regions from the network previously underutilized. Our middle-aged individuals, when compared to the younger healthy adult group, presented lower levels of activation intensity and connectivity strength, with no recruitment of additional regions, possibly reflecting an initial, uncompensated, network decline. In contrast, the DMN presented a gradual decrease in deactivation intensity and deactivation extent (i.e., low in the middle-aged, and lower in the old) and similar gradual reduction of functional connectivity within the network, with no compensation. The patterns of age-related changes in the task-relevant system and DMN are incongruent with the previously suggested notion of anti-correlation of the two systems. The context-dependent correlation by psycho-physiological interaction (PPI) analysis demonstrated an independence of these two systems, with the onset of task not influencing the correlation between the two systems. Our results suggest that the language network and the DMN may be non-dependent systems, potentially correlated through the re-allocation of cortical resources, and that aging may affect those two systems differently.

  • Low functional robustness in mesial temporal lobe epilepsy.

    C Garcia-Ramos, J Song, B P Hermann, V Prabhakaran
    Epilepsy research, Apr 16, 2016 PMID: 27082649
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    Brain functional topology was investigated in patients with mesial temporal lobe epilepsy (mTLE) by means of graph theory measures in two differentially defined graphs. Measures of segregation, integration, and centrality were compared between subjects with mTLE and healthy controls (HC).

  • Graph theory and cognition: A complementary avenue for examining neuropsychological status in epilepsy.

    Camille Garcia-Ramos, Jack J Lin, Tanja S Kellermann, Leonardo Bonilha, Vivek Prabhakaran, Bruce P Hermann
    Epilepsy & behavior : E&B, Mar 28, 2016 PMID: 27017326
    Show Summary

    The recent revision of the classification of the epilepsies released by the ILAE Commission on Classification and Terminology (2005-2009) has been a major development in the field. Papers in this section of the special issue explore the relevance of other techniques to examine, categorize, and classify cognitive and behavioral comorbidities in epilepsy. In this review, we investigate the applicability of graph theory to understand the impact of epilepsy on cognition compared with controls and, then, the patterns of cognitive development in normally developing children which would set the stage for prospective comparisons of children with epilepsy and controls. The overall goal is to examine the potential utility of this analytic tool and approach to conceptualize the cognitive comorbidities in epilepsy. Given that the major cognitive domains representing cognitive function are interdependent, the associations between neuropsychological abilities underlying these domains can be referred to as a cognitive network. Therefore, the architecture of this cognitive network can be quantified and assessed using graph theory methods, rendering a novel approach to the characterization of cognitive status. We first provide fundamental information about graph theory procedures, followed by application of these techniques to cross-sectional analysis of neuropsychological data in children with epilepsy compared with that of controls, concluding with prospective analysis of neuropsychological development in younger and older healthy controls. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy".

  • Developmental Reorganization of the Cognitive Network in Pediatric Epilepsy.

    Camille Garcia-Ramos, Jack J Lin, Vivek Prabhakaran, Bruce P Hermann
    PloS one, Oct 28, 2015 PMID: 26505900
    Show Summary

    Traditional approaches to understanding cognition in children with epilepsy (CWE) involve cross-sectional or prospective examination of diverse test measures, an approach that does not inform the interrelationship between different abilities or how interrelationships evolve prospectively. Here we utilize graph theory techniques to interrogate the development of cognitive landmarks in CWE and healthy controls (HC) using the two-year percentage change across 20 tests. Additionally, we characterize the development of cognition using traditional analyses, showing that CWE perform worse at baseline, develop in parallel with HC, statically maintaining cognitive differences two years later. Graph analyses, however, showed CWE to exhibit both lower integration and segregation in development of their cognitive networks compared to HC. In conclusion, graph analyses of neuropsychological data capture a dynamic and changing complexity in the interrelationships among diverse cognitive skills, maturation of the cognitive network over time, and the nature of differences between normally developing children and CWE.

  • Regional homogeneity (ReHo) changes in new onset versus chronic benign epilepsy of childhood with centrotemporal spikes (BECTS): A resting state fMRI study.

    Hongwu Zeng, Camille Garcia Ramos, Veena A Nair, Yan Hu, Jianxiang Liao, Christian La, Li Chen, Yungen Gan, Feiqiu Wen, Bruce Hermann, Vivek Prabhakaran
    Epilepsy research, Sep 11, 2015 PMID: 26354170
    Show Summary

    The purpose of this study was to investigate regional homogeneity (ReHo) in children with new-onset drug-naïve Benign Epilepsy with Centrotemporal Spikes (BECTS), chronic BECTS and healthy controls (HC) using the Regional Homogeneity (ReHo) method applied to resting state fMRI data.

  • Cognition and brain development in children with benign epilepsy with centrotemporal spikes.

    Camille Garcia-Ramos, Daren C Jackson, Jack J Lin, Kevin Dabbs, Jana E Jones, David A Hsu, Carl E Stafstrom, Lucy Zawadzki, Michael Seidenberg, Vivek Prabhakaran, Bruce P Hermann
    Epilepsia, Sep 05, 2015 PMID: 26337046
    Show Summary

    Benign epilepsy with centrotemporal spikes (BECTS), the most common focal childhood epilepsy, is associated with subtle abnormalities in cognition and possible developmental alterations in brain structure when compared to healthy participants, as indicated by previous cross-sectional studies. To examine the natural history of BECTS, we investigated cognition, cortical thickness, and subcortical volumes in children with new/recent onset BECTS and healthy controls (HC).

  • Individual classification of children with epilepsy using support vector machine with multiple indices of diffusion tensor imaging.

    Ishmael Amarreh, Mary E Meyerand, Carl Stafstrom, Bruce P Hermann, Rasmus M Birn
    NeuroImage. Clinical, Jun 18, 2014 PMID: 24936426
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    Support vector machines (SVM) have recently been demonstrated to be useful for voxel-based MR image classification. In the present study we sought to evaluate whether this method is feasible in the classification of childhood epilepsy intractability based on diffusion tensor imaging (DTI), with adequate accuracy. We applied SVM in conjunction DTI indices of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). DTI studies have reported white matter abnormalities in childhood-onset epilepsy, but the mechanisms underlying these abnormalities are not well understood. The aim of this study was to examine the relationship between epileptic seizures and cerebral white matter abnormalities identified by DTI in children with active compared to remitted epilepsy utilizing an automated and unsupervised classification method.

  • Cerebral white matter integrity in children with active versus remitted epilepsy 5 years after diagnosis.

    Ishmael Amarreh, Kevin Dabbs, Daren C Jackson, Jana E Jones, Mary E Meyerand, Carl E Stafstrom, David A Hsu, Michael Seidenberg, Bruce P Hermann
    Epilepsy research, Oct 24, 2013 PMID: 24148888
    Show Summary

    Diffusion tensor imaging (DTI) studies have reported white matter abnormalities in childhood-onset epilepsy, but the mechanisms and timing underlying these abnormalities, and their resolution, are not well understood. This study examined white matter integrity in children with active versus remitted epilepsy.

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