Patterns of altered functional connectivity in mesial temporal lobe epilepsy

Abstract

SUMMARYPurpose: In mesial temporal lobe epilepsy (MTLE) the epileptogenic area is confined to the mesial temporal lobe, but other cortical and subcortical areas are also affected and cognitive and psychiatric impairments are usually documented. Functional connectivity methods are based on the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which exhibit consistent and reproducible functional networks from resting state data. The aim of this study is to compare functional connectivity of patients with MTLE during the interictal period with healthy subjects. We hypothesize that patients show reduced functional connectivity compared to controls, the interest being to determine which regions show this reduction. Methods: We selected electroencephalography-functional magnetic resonance imaging (EEG-fMRI) resting state data without EEG spikes from 16 patients with right and 7 patients with left MTLE. EEG-fMRI resting state data of 23 healthy subjects matched for age, sex, and manual preference were selected as controls. Four volumes of interest in the left and right amygdalae and hippocampi (LA, RA, LH, and RH) were manually segmented in the anatomic MRI of each subject. The averaged BOLD time course within each volume of interest was used to detect brain regions with BOLD signal correlated with it. Group differences between patients and controls were estimated.Key Findings: In patients with right MTLE, group difference functional connectivity maps (RMTLE ) controls) showed for RA and RH decreased connectivity with the brain areas of the default mode network (DMN), the ventromesial limbic prefrontal regions, and contralateral mesial temporal structures; and for LA and LH, decreased connectivity with DMN and contralateral hippocampus. Additional decreased connectivity was found between LA and pons and between LH and ventromesial limbic prefrontal structures. In patients with left MTLE, functional connectivity maps (LMTLE ) controls) showed for LA and LH decreased connectivity with DMN, contralateral hippocampus, and bilateral ventromesial limbic prefrontal regions; no change in connectivity was detected for RA; and for RH, there was decreased connectivity with DMN, bilateral ventromesial limbic prefrontal regions, and contralateral amygdala and hippocampus. Significance: In unilateral MTLE, amygdala and hippocampus on the affected and to a lesser extent on the healthy side are less connected, and are also less connected with the dopaminergic mesolimbic and the DMNs. Changes in functional connectivity between mesial temporal lobe structures and these structures may explain cognitive and psychiatric impairments often found in patients with MTLE.

Functional Networks in Temporal-Lobe Epilepsy: A Voxel-Wise Study of Resting-State Functional Connectivity and Gray-Matter Concentration

“…However, at lower thresholds, we found decreased functional connectivity in patients in at least one region in the frontal superior medial gyrus near regions of decreased connectivity to a manually drawn seed region in the LH detected by Pittau et al (2012). We also found decreased connectivity in LTLE in the right posterior cingulate similar to Periera et al (2010).…”

Network Analysis of the Default Mode Network Using Functional Connectivity MRI in Temporal Lobe Epilepsy

“…Such a secondary involvement of the DMN may also be causative for the clinical effects of other conditions affecting the temporal lobe/ limbic system such as schizophrenia 25 and Alzheimer's disease 22,26 . Prior studies have shown DMN involvement in TLE and other forms of epilepsy during seizures, during interictal epileptiform discharges, and in the interictal state 9,[28][29][30][31][32][33] . These studies indicate a potentially important role of the DMN in the interictal electrographic and the ictal behavioral characteristics of TLE.…”

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

“…1 Application of connectivity principles to these data has promoted research in various aspects of epileptic seizures, and there has been overwhelming report of decreased connectivity around the seizure-onset zone [2][3][4][5][6] and the default mode network (DMN) by several groups. 7,8 In 2012, Jehi 7 and Morgan et al 9 reported that connectivity patterns were different in patients with right and left mesial temporal sclerosis and that there was decreased connectivity between the regions of the DMN and the hippocampus and amygdala in patients with mesial temporal sclerosis.…”