Resting functional connectivity between the hemispheres in childhood absence epilepsy

Abstract

Objective:The fundamental mechanisms by which childhood absence epilepsy (CAE) changes neural networks even between seizures remain poorly understood. During seizures, cortical and subcortical networks exhibit bihemspheric synchronous activity based on prior EEG-fMRI studies. Our aim was to investigate whether this abnormal bisynchrony may extend to the interictal period, using a blood oxygen level-dependent (BOLD) resting functional connectivity approach.Methods: EEG-fMRI data were recorded from 16 patients with CAE and 16 age-and gendermatched controls. Three analyses were performed. 1) Using 16 pairs of seizure-related regions of interest (ROI), we compared the between-hemisphere interictal resting functional connectivity of patients and controls. 2) For regions showing significantly increased interhemispheric connectivity in CAE, we then calculated connectivity to the entire brain. 3) A paired-voxel approach was performed to calculate resting functional connectivity between hemispheres without the constraint of predefined ROIs. Results:We found significantly increased resting functional connectivity between hemispheres in the lateral orbitofrontal cortex of patients with CAE compared to normal controls. Enhanced between-hemisphere connectivity localized to the lateral orbitofrontal cortex was confirmed by all 3 analysis methods.Conclusions: Our results demonstrate abnormal increased connectivity between the hemispheres in patients with CAE in seizure-related regions, even when seizures were not occurring. These findings suggest that the lateral orbitofrontal cortex may play an important role in CAE pathophysiology, warranting further investigation. In addition, resting functional connectivity analysis may provide a promising biomarker to improve our understanding of altered brain function in CAE during the interictal period. Neurology Childhood absence epilepsy (CAE) is increasingly recognized as a disorder characterized by impaired function both during seizures, and in the interictal period.1-4 Notably, 3-4 Hz spikewave discharges (SWD) seen in CAE 5-7 and their associated blood oxygenation level-dependent (BOLD) fMRI changes [8][9][10][11][12][13][14][15][16] are bilateral and fairly symmetric. Evidence from animal models indicates that this bihemispheric synchrony during SWD is mediated by the corpus callosum. 17,18 We hypothesize that abnormal bihemispheric synchrony persists in the interictal period, and may participate in generating abnormal function, including enhanced bilateral excitability. The possible role of abnormal long-range bilateral synchrony during the interictal period in CAE has not been previously investigated.The recent development of the resting functional connectivity approach to fMRI has provided a window to observe intrinsic brain activity in health and disease. This method has been used to

Identifying Corticothalamic Network Epicenters in Patients with Idiopathic Generalized Epilepsy

“…Brain regions with high FCS are network hubs that facilitate the integration and propagation of neural processing. 19 Increased FCS in patients with IGE is consistent with a high excitatory state or neuronal synchronization 22 and suggests that certain brain regions may be responsible for rapidly spreading the generalized spike-waves to all areas.…”

Seizure Frequency Can Alter Brain Connectivity: Evidence from Resting-State fMRI

“…We found that patients in the frequent-seizure group had increased connections within the temporal lobes bilaterally involving the seizure-prone medial temporal structure and bilateral primary auditory cortex, and those in the infrequent-seizure group had increased connections of the DMN. Observations of increased connectivity with other types of epilepsy, such as in the medial temporal lobes with mesial temporal sclerosis, 8,10 the lateral orbitofrontal lobes with absence seizures, 37 and frontal lobes with idiopathic generalized epilepsy, 38,39 make us surmise that increased connections are probably more specific to understand epileptogenesis. Previous studies also pointed to a temporal lobe origin in 67%-100% of patients with HWE.…”

The zona incerta modulates spontaneous spike-wave discharges in the rat

“…In particular, the perioral sensorimotor cortical area is a minimal neural substrate for the generation of absence seizures and myoclonus (Chen et al 2011;Fanselow et al 2001;Semba and Komisaruk 1984). The concept of focal cortical abnormality can be further supported by the elevation of interhemisphere functional connectivity of the lateral orbitofrontal cortex of patients with childhood absence epilepsy (Bai et al 2011). Rhythmic activities of the cortex and thalamic VPM are continuous throughout a SWD, and cortical neurons are phase ahead of the VPM during SWDs (Meeren et al 2002;Nicolelis et al 1995;Pinault et al 2006).…”