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Low functional robustness in mesial temporal lobe epilepsy.

ABSTRACT: 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.

SUBMITTER: Garcia-Ramos C

PROVIDER: S-EPMC4867275 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Low functional robustness in mesial temporal lobe epilepsy.

Garcia-Ramos C C Song J J Hermann B P BP Prabhakaran V V

Epilepsy research 20160405

<h4>Objectives</h4>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).<h4>Methods</h4>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 matri ...[more]

PMID: 27082649

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Project description: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.

Project description:The epilepsies represent one of the most common neurological disorders. Mesial temporal lobe epilepsies (MTLE) are the most frequent form of partial epilepsies and display frequent resistance to anti-epileptic drugs thus representing a major health care problem. In TLE, the origin of seizure activity typically involves the hippocampal formation, which displays major neuropathological features, described with the term hippocampal sclerosis (HS). HS is the most frequent pathological substrate of refractory mesial temporal lobe epilepsy. Complex partial seizures (CPS) are the predominant seizure type associated with medial temporal lobe epilepsy. MTLE is commonly due to mesial temporal sclerosis (MTS). The biology underlying the epilepstic seizures and the transcriptome associated to the seizure in intractable medial temporal lobe epilepsy is ill understood. The aim of the study was to identify potential biomarkers that could identify epileptic seizure. Thus we performed transcriptome profiling of ten medial temporal lobe epilepsy cases which are resistant to the drug and underwent temporal lobectomy. The cases constitutes of patients with intractable complex partial seizure, treated medically and have undergone detailed presurgical evaluation and subjected to surgery for standard temporal lobectomy and amygdalo-hippocampectomy. The spiking areas identified after the electrocorticography will form the test tissues, which compared with the nonspiking areas removed during the surgery, from the same patient. This could probably form one of the appropriate controls, as test and control are from same patient, which eliminates the genome variations that could incur due to the comparison with the tissues from the another patient. Also this could get rid of expression changes due to the treatments undergone by the patient. We performed two color microarray wherein we labled seizure focus (spiking area) with Cy5 and non-seizure region tissues (non-spiking) with Cy3. As a strategy to test the possibility of potential diagnostic biomarkers we are intended to test the differentially regulated molecules in an independent set of epilepsy samples. Two color experiment

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Low functional robustness in mesial temporal lobe epilepsy.

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Low functional robustness in mesial temporal lobe epilepsy.

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