Alterations in the functional brain network in a rat model of epileptogenesis: A longitudinal resting state fMRI study

Emma Christiaen; Marie-Gabrielle Goossens; Robrecht Raedt; Benedicte Descamps; Lars Emil Larsen; Erine Craey; Evelien Carrette; Kristl Vonck; Paul Boon; Christian Vanhove

doi:10.1016/j.neuroimage.2019.116144

Alterations in the functional brain network in a rat model of epileptogenesis: A longitudinal resting state fMRI study

Neuroimage. 2019 Nov 15:202:116144. doi: 10.1016/j.neuroimage.2019.116144. Epub 2019 Aug 29.

Authors

Affiliations

¹ MEDISIP, Department of Electronics and Information Systems, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium. Electronic address: emma.christiaen@ugent.be.
² 4Brain Team, Department of Head and Skin, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium. Electronic address: mariegabrielle.goossens@ugent.be.
³ 4Brain Team, Department of Head and Skin, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium. Electronic address: robrecht.raedt@ugent.be.
⁴ MEDISIP, Department of Electronics and Information Systems, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium. Electronic address: benedicte.descamps@ugent.be.
⁵ MEDISIP, Department of Electronics and Information Systems, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium; 4Brain Team, Department of Head and Skin, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium. Electronic address: larsemil.larsen@ugent.be.
⁶ 4Brain Team, Department of Head and Skin, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium. Electronic address: erine.craey@ugent.be.
⁷ 4Brain Team, Department of Head and Skin, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium. Electronic address: evelien.carrette@uzgent.be.
⁸ 4Brain Team, Department of Head and Skin, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium. Electronic address: kristl.vonck@ugent.be.
⁹ 4Brain Team, Department of Head and Skin, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium. Electronic address: paul.boon@uzgent.be.
¹⁰ MEDISIP, Department of Electronics and Information Systems, Ghent University, Corneel Heymanslaan 10, Ghent, Belgium. Electronic address: christian.vanhove@ugent.be.

PMID: 31473355
DOI: 10.1016/j.neuroimage.2019.116144

Abstract

Epilepsy is a neurological disorder characterized by recurrent epileptic seizures. Electrophysiological and neuroimaging studies in patients with epilepsy suggest that abnormal functional brain networks play a role in the development of epilepsy, i.e. epileptogenesis, resulting in the generation of spontaneous seizures and cognitive impairment. In this longitudinal study, we investigated changes in functional brain networks during epileptogenesis in the intraperitoneal kainic acid (IPKA) rat model of temporal lobe epilepsy (TLE) using resting state functional magnetic resonance imaging (rsfMRI) and graph theory. Additionally, we investigated whether these changes are related to the frequency of occurrence of spontaneous epileptic seizures in the chronic phase of epilepsy. Using a 7T MRI system, rsfMRI images were acquired under medetomidine anaesthesia before and 1, 3, 6, 10 and 16 weeks after status epilepticus (SE) induction in 20 IPKA animals and 7 healthy control animals. To obtain a functional network, correlation between fMRI time series of 38 regions of interest (ROIs) was calculated. Then, several graph theoretical network measures were calculated to describe and quantify the network changes. At least 17 weeks post-SE, IPKA animals were implanted with electrodes in the left and right dorsal hippocampus, EEG was measured for 7 consecutive days and spontaneous seizures were counted. Our results show that correlation coefficients of fMRI time series shift to lower values during epileptogenesis, indicating weaker whole brain network connections. Segregation and integration in the functional brain network also decrease, indicating a lower local interconnectivity and a lower overall communication efficiency. Secondly, this study demonstrates that the largest decrease in functional connectivity is observed for the retrosplenial cortex. Finally, post-SE changes in functional connectivity, segregation and integration are correlated with seizure frequency in the IPKA rat model.

Keywords: Functional connectivity; Graph theory; Intraperitoneal kainic acid rat model; Resting state functional MRI; Temporal lobe epilepsy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / drug effects
Brain / physiopathology*
Brain Mapping
Disease Models, Animal
Epilepsy, Temporal Lobe / chemically induced
Epilepsy, Temporal Lobe / physiopathology*
Hippocampus / drug effects
Hippocampus / pathology
Image Processing, Computer-Assisted
Kainic Acid / administration & dosage
Longitudinal Studies
Magnetic Resonance Imaging
Male
Neural Pathways / drug effects
Neural Pathways / physiopathology
Rats, Sprague-Dawley
Seizures / chemically induced
Seizures / physiopathology*

Substances

Kainic Acid