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Patterns of altered functional connectivity in mesial temporal lobe epilepsy.

ABSTRACT: 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.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.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.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.

SUBMITTER: Pittau F

PROVIDER: S-EPMC3767602 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Patterns of altered functional connectivity in mesial temporal lobe epilepsy.

Pittau Francesca F Grova Christophe C Moeller Friederike F Dubeau François F Gotman Jean J

Epilepsia 20120511 6

<h4>Purpose</h4>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 compar ...[more]

PMID: 22578020

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Project description:OBJECTIVES: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). METHODS:Eleven subjects with mTLE (age 36.5±10.9years) and 15 age-matched HC (age 36.8±14.0years) participated in this study. Both anatomically and functionally defined adjacency matrices were used to investigate the measures. Binary undirected graphs were constructed to study network segregation by calculating global clustering and modularity, and network integration by calculating local and global efficiency. Node degree and participation coefficient were also computed in order to investigate network hubs and their classification into provincial or connector hubs. Measures were investigated in a range of low to medium graph density. RESULTS:The group of patients presented lower global segregation than HC while showing higher global but lower local integration. They also failed to engage regions that comprise the default-mode network (DMN) as hubs such as bilateral medial frontal regions, PCC/precuneus complex, and right inferior parietal lobule, which were present in controls. Furthermore, the cerebellum in subjects with mTLE seemed to be playing a major role in the integration of their functional networks, which was evident through the engagement of cerebellar regions as connector hubs. CONCLUSIONS:Functional networks in subjects with mTLE presented both global and local abnormalities compared to healthy subjects. Specifically, there was significant separation between groups, with lower global segregation and slightly higher global integration observed in patients. This could be indicative of a network that is working as a whole instead of in segregated or specialized communities, which could translate into a less robust network and more prone to disruption in the group with epilepsy. Furthermore, functional irregularities were also observed in the group of patients in terms of the engagement of cerebellar regions as hubs while failing to engage DMN-related areas as major hubs in the network. The use of two differentially defined graphs synergistically contributed to findings.

Project description:Background and purposeAlthough most studies on epilepsy have focused on the epileptogenic zone, epilepsy is a system-level disease characterized by aberrant neuronal synchronization among groups of neurons. Increasingly, studies have indicated that mesial temporal lobe epilepsy may be a network-level disease; however, few investigations have examined resting-state functional connectivity of the entire brain, particularly in patients with mesial temporal lobe epilepsy and hippocampal sclerosis. This study primarily investigated whole-brain resting-state functional connectivity abnormality in patients with mesial temporal lobe epilepsy and right hippocampal sclerosis during the interictal period.Materials and methodsWe investigated resting-state functional connectivity of 21 patients with mesial temporal lobe epilepsy with right hippocampal sclerosis and 21 neurologically healthy controls. A multivariate pattern analysis was used to identify the functional connections that most clearly differentiated patients with mesial temporal lobe epilepsy with right hippocampal sclerosis from controls.ResultsDiscriminative analysis of functional connections indicated that the patients with mesial temporal lobe epilepsy with right hippocampal sclerosis exhibited decreased resting-state functional connectivity within the right hemisphere and increased resting-state functional connectivity within the left hemisphere. Resting-state network analysis suggested that the internetwork connections typically obey the hemispheric lateralization trend and most of the functional connections that disturb the lateralization trend are the intranetwork ones.ConclusionsThe current findings suggest that weakening of the resting-state functional connectivity associated with the right hemisphere appears to strengthen resting-state functional connectivity on the contralateral side, which may be related to the seizure-induced damage and underlying compensatory mechanisms. Resting-state network-based analysis indicated that the compensatory mechanism among different resting-state networks may disturb the hemispheric lateralization.

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Patterns of altered functional connectivity in mesial temporal lobe epilepsy.

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Patterns of altered functional connectivity in mesial temporal lobe epilepsy.

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