A generalized epilepsy network derived from brain abnormalities and deep brain stimulation
Poster No:
1738
Submission Type:
Abstract Submission
Authors:
Gong-Jun Ji1, Michael Fox2, Mae Morton-Dutton2, Yingru Wang3, Jinmei Sun4, Panpan Hu5, Xingui Chen5, Zhiqiang Zhang6, Haya Akkad2, Janne Nordberg7, Juho Joutsa7, Cristina Torres Diaz8, Sergiu Groppa7, Gabriel Gonzalez-Escamilla7, Linda Dalic9, John Archer10, Aaron Warren2, Melissa Chua2, Alexander Cohen2, Sara Larivière2, Clemens Neudorfer2, Andreas Horn2, Rani Sarkis2, Ellen Bubrick2, Robert Fisher11, John Rolston2, Kai Wang4, Frederic Schaper2
Institutions:
1Anhui Medical University, Hefei, Anhui Province, 2Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 3Anhui Medical University, Hefei, Anhui , 4Anhui Medical University, Hefei, Anhui, 5The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, 6Jinling Hospital, the First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu, 7Department of Clinical Neurophysiology, Turku University Hospital, Turku, Pori, 8Hospital Universitario La Princesa, Universidad Autónoma de Madrid, Madrid, Madrid, 9The University of Melbourne, Victoria, Victoria, 10The University of Melbourne, Victoria, Victoria, 11Stanford University School of Medicine, Palo Alto, California
First Author:
Co-Author(s):
Panpan Hu
The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
Hefei, Anhui
The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
Hefei, Anhui
Xingui Chen
The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
Hefei, Anhui
The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
Hefei, Anhui
Zhiqiang Zhang
Jinling Hospital, the First School of Clinical Medicine, Southern Medical University
Nanjing, Jiangsu
Jinling Hospital, the First School of Clinical Medicine, Southern Medical University
Nanjing, Jiangsu
Cristina Torres Diaz
Hospital Universitario La Princesa, Universidad Autónoma de Madrid
Madrid, Madrid
Hospital Universitario La Princesa, Universidad Autónoma de Madrid
Madrid, Madrid
Gabriel Gonzalez-Escamilla
Department of Clinical Neurophysiology, Turku University Hospital
Turku, Pori
Department of Clinical Neurophysiology, Turku University Hospital
Turku, Pori
Introduction:
Patients with idiopathic generalized epilepsy (IGE) show distributed subtle brain abnormalities. However, it is unknown if these abnormalities occur within a common brain network and whether they can inform network therapies such as deep brain stimulation (DBS).
Methods:
We performed a systematic search and retrieved all published coordinates of brain abnormalities (atrophy or fMRI hyperactivity) associated with IGE (n = 21 studies, including 540 IGE patients and 778 healthy controls). We computed the functional connections of these abnormal coordinates on the healthy connectome of 652 Asian adults (validated by Western connectome and pediatric connectome) using a novel technique termed coordinate network mapping. The resulting coordinate networks were overlapped to identify a common IGE network across all studies. Voxel-wise statistical analyses were performed using the PALM function in FSL (V6.0.4). We considered an FDR-corrected two-sided P < 0.05 as significant.
Results:
The coordinates of brain abnormalities in IGE are highly heterogeneous between studies, but their functional connectivities were highly overlapped in a common brain network (Fig. 1A) with positive connectivity to the somato-cognitive action network (SCAN) regions and negative connectivity to the default mode regions. This overlapping network was specific to IGE as compared to coordinates in neurodegenerative disease (n=49, from Darby et al., 2019, Brain) or random coordinates (n=63) (P < 0.05, Fig. 1B). Hereafter, we termed the overlapping map as IGE network.
To further validate the IGE network, we searched the literature for simultaneous EEG-fMRI studies in generalized and focal epilepsies reported coordinates activated by (inter)ictal discharges. We found 7 studies with generalized epilepsy and 6 studies with focal epilepsy. Brain regions activated with (inter)ictal discharges in generalized epilepsy overlapped more with our IGE network than regions activated in focal epilepsy (t = 2.83, P = 0.017, Fig. 1C).
To explain the involuntary movements of the whole body rather than any single hand or leg during generalized seizures, we tested whether our IGE network affected the (inter)effector regions in the primary motor area more than the effector regions of leg, hand, and mouth as defined by Gordon et al. (2023, Nature). This hypothesis was supported by the comparison between inter-effector and effector regions (t = 3.96, P = 0.003, Fig. 1D).
To test the therapeutic relevance of our IGE network, we analyzed two independent datasets of DBS sites from 27 patients with generalized seizures who received thalamic centromedian (CM)-DBS. Thalamic centromedian (CM)-DBS electrode locations differed between patients (Fig. 2A), as did the magnitude of seizure control after DBS. The IGE network involved functional connectivity to the CM, and more specifically peaked at the anterolateral part of the CM bordering the ventral lateral posterior (ventral subdivision, VLPv) thalamic nucleus (Fig. 2B-C). Higher CM-DBS stimulation site (i.e., volume of activated tissue [VAT]) overlap with our IGE network was associated with better seizure control (Spearman R = 0.44, P = 0.019, Fig. 2D). In contrast, no association was found between seizure control and VAT volume, VAT overlap with the CM or ALE results.
To further validate the IGE network, we searched the literature for simultaneous EEG-fMRI studies in generalized and focal epilepsies reported coordinates activated by (inter)ictal discharges. We found 7 studies with generalized epilepsy and 6 studies with focal epilepsy. Brain regions activated with (inter)ictal discharges in generalized epilepsy overlapped more with our IGE network than regions activated in focal epilepsy (t = 2.83, P = 0.017, Fig. 1C).
To explain the involuntary movements of the whole body rather than any single hand or leg during generalized seizures, we tested whether our IGE network affected the (inter)effector regions in the primary motor area more than the effector regions of leg, hand, and mouth as defined by Gordon et al. (2023, Nature). This hypothesis was supported by the comparison between inter-effector and effector regions (t = 3.96, P = 0.003, Fig. 1D).
To test the therapeutic relevance of our IGE network, we analyzed two independent datasets of DBS sites from 27 patients with generalized seizures who received thalamic centromedian (CM)-DBS. Thalamic centromedian (CM)-DBS electrode locations differed between patients (Fig. 2A), as did the magnitude of seizure control after DBS. The IGE network involved functional connectivity to the CM, and more specifically peaked at the anterolateral part of the CM bordering the ventral lateral posterior (ventral subdivision, VLPv) thalamic nucleus (Fig. 2B-C). Higher CM-DBS stimulation site (i.e., volume of activated tissue [VAT]) overlap with our IGE network was associated with better seizure control (Spearman R = 0.44, P = 0.019, Fig. 2D). In contrast, no association was found between seizure control and VAT volume, VAT overlap with the CM or ALE results.
·Figure 1. IGE network mapping
·Figure 2. Relevance for deep brain stimulation.
Conclusions:
This generalized epilepsy network could be a novel network target and guide clinical trials of (non)invasive brain stimulation to control generalized seizures.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 2
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 1
Keywords:
Epilepsy
FUNCTIONAL MRI
STRUCTURAL MRI
1|2Indicates the priority used for review
Provide references using author date format
Gordon, E.M., (2023), 'A somato-cognitive action network alternates with effector regions in motor cortex', Nature, vol. 617, no. 7960, pp. 351-359.