Simultaneous Intracranial EEG-fMRI Shows Inter-Modality Correlation in Time-Resolved Connectivity Within Normal Areas but Not Within Epileptic Regions.

For the first time in research in humans, we used simultaneous icEEG-fMRI to examine the link between connectivity in haemodynamic signals during the resting-state (rs) and connectivity derived from electrophysiological activity in terms of the inter-modal connectivity correlation (IMCC). We quantified IMCC in nine patients with drug-resistant epilepsy (i) within brain networks in 'healthy' non-involved cortical zones (NIZ) and (ii) within brain networks involved in generating seizures and interictal spikes (IZ1) or solely spikes (IZ2). Functional connectivity (h 2 ) estimates for 10 min of resting-state data were obtained between each pair of electrodes within each clinical zone for both icEEG and fMRI. A sliding window approach allowed us to quantify the variability over time of h 2 (vh 2) as an indicator of connectivity dynamics. We observe significant positive IMCC for h 2 and vh 2, for multiple bands in the NIZ only, with the strongest effect in the lower icEEG frequencies. Similarly, intra-modal h 2 and vh 2 were found to be differently modified as a function of different epileptic processes: compared to NIZ, [Formula: see text] was higher in IZ1, but lower in IZ2, while [Formula: see text] showed the inverse pattern. This corroborates previous observations of inter-modal connectivity discrepancies in pathological cortices, while providing the first direct invasive and simultaneous comparison in humans. We also studied time-resolved FC variability multimodally for the first time, finding that IZ1 shows both elevated internal [Formula: see text] and less rich dynamical variability, suggesting that its chronic role in epileptogenesis may be linked to greater homogeneity in self-sustaining pathological oscillatory states.

Hyperactivation of parahippocampal region and fusiform gyrus associated with successful encoding in medial temporal lobe epilepsy.

PURPOSE: Performance in recognition memory differs among patients with medial temporal lobe epilepsy (MTLE). We aimed to determine if distinct recognition performances (normal vs. impaired) could be related to distinct patterns of brain activation during encoding. METHODS: Event-related functional magnetic resonance imaging (fMRI) activation profiles were obtained during successful encoding of non-material-specific items, in 14 MTLE patients tested for recognition of stimuli afterward. Findings were compared to those of 25 healthy subjects, and voxel-based correlations were assessed between brain activation and performance. KEY FINDINGS: Patients with left and right MTLE showed similar activations and similar performances. As a whole, the group of patients demonstrated altered recognition scores, but three of the seven patients with left MTLE and three of the seven patients with right MTLE exhibited normal performance relative to controls. In comparison to healthy subjects and patients with impaired recognition, patients with normal recognition showed weaker activations in left opercular cortex, but stronger activations in bilateral parahippocampal region/fusiform gyrus (PH/FG). By contrast, patients with impaired performance showed weaker activations in bilateral PH/FG, but stronger activations in a frontal/cingulate and parietal network. Recognition performance was correlated positively to bilateral PH/FG activations, and negatively correlated to bilateral frontal/cingulate activations, in the whole group of patients, as well as in subgroups of patients with either left or right MTLE. SIGNIFICANCE: These results suggest occurrence of effective functional compensation within bilateral PH/FG in MTLE, allowing patients to maintain recognition capability. In contrast, impairment of this perceptive-memory system may lead to alternative activation of an inefficient nonspecific attentional network in patients with altered performance.

Role of resting state functional connectivity MRI in presurgical investigation of mesial temporal lobe epilepsy.

OBJECTIVE: The authors aimed to determine the ability of resting-state functional connectivity MRI (fcMRI) to lateralise/localise the epileptogenic zone in patients presenting with mesial temporal lobe epilepsy (MTLE) at the individual level. METHODS: Basal functional connectivity (BFC) was evaluated in each hemisphere of 22 MTLE patients. 200 volumes were acquired using a single-shot GE-EPI sequence during a resting period of 10 min at 1.5 T. The signal time-course was extracted from 10 regions of interest (ROIs), five ROIs in each hemisphere, usually involved in epileptogenic networks of MTLE. Normalised correlation coefficients between pairs of ROIs signal time-courses were computed to reflect BFC. Based on normative BFC values obtained from 36 controls, the number of BFC decreases and increases were determined in each hemisphere for each patient. RESULTS: BFC decreases were found bilaterally, although the number of decreased links was significantly higher in the epileptogenic side (p=0.025). Conversely, BFC increases were found almost exclusively in the contralateral lobe leading to a strong test effect for locating the non-epileptic lobe with a sensitivity of 64% and a specificity of 91% (p<0.001). The most frequently disconnected areas were the entorhinal cortex and the anterior hippocampus in the epileptic lobe, while contralateral BFC increases involved preferentially hippocampus and amygdala. CONCLUSIONS: This study demonstrates that the presence of BFC increases in the non-epileptic side was paradoxically the most specific marker of epileptogenic zone localisation, and suggests that a single resting-state fcMRI could be useful in the presurgical assessment of MTLE at an individual level.

Graph theoretical analysis of structural and functional connectivity MRI in normal and pathological brain networks.

Graph theoretical analysis of structural and functional connectivity MRI data (ie. diffusion tractography or cortical volume correlation and resting-state or task-related (effective) fMRI, respectively) has provided new measures of human brain organization in vivo. The most striking discovery is that the whole-brain network exhibits "small-world" properties shared with many other complex systems (social, technological, information, biological). This topology allows a high efficiency at different spatial and temporal scale with a very low wiring and energy cost. Its modular organization also allows for a high level of adaptation. In addition, degree distribution of brain networks demonstrates highly connected hubs that are crucial for the whole-network functioning. Many of these hubs have been identified in regions previously defined as belonging to the default-mode network (potentially explaining the high basal metabolism of this network) and the attentional networks. This could explain the crucial role of these hub regions in physiology (task-related fMRI data) as well as in pathophysiology. Indeed, such topological definition provides a reliable framework for predicting behavioral consequences of focal or multifocal lesions such as stroke, tumors or multiple sclerosis. It also brings new insights into a better understanding of pathophysiology of many neurological or psychiatric diseases affecting specific local or global brain networks such as epilepsy, Alzheimer's disease or schizophrenia. Graph theoretical analysis of connectivity MRI data provides an outstanding framework to merge anatomical and functional data in order to better understand brain pathologies.

Decreased basal fMRI functional connectivity in epileptogenic networks and contralateral compensatory mechanisms.

A better understanding of interstructure relationship sustaining drug-resistant epileptogenic networks is crucial for surgical perspective and to better understand the consequences of epileptic processes on cognitive functions. We used resting-state fMRI to study basal functional connectivity within temporal lobes in medial temporal lobe epilepsy (MTLE) during interictal period. Two hundred consecutive single-shot GE-EPI acquisitions were acquired in 37 right-handed subjects (26 controls, eight patients presenting with left and three patients with right MTLE). For each hemisphere, normalized correlation coefficients were computed between pairs of time-course signals extracted from five regions involved in MTLE epileptogenic networks (Brodmann area 38, amygdala, entorhinal cortex (EC), anterior hippocampus (AntHip), and posterior hippocampus (PostHip)). In controls, an asymmetry was present with a global higher connectivity in the left temporal lobe. Relative to controls, the left MTLE group showed disruption of the left EC-AntHip link, and a trend of decreased connectivity of the left AntHip-PostHip link. In contrast, a trend of increased connectivity of the right AntHip-PostHip link was observed and was positively correlated to memory performance. At the individual level, seven out of the eight left MTLE patients showed decreased or disrupted functional connectivity. In this group, four patients with left TLE showed increased basal functional connectivity restricted to the right temporal lobe spared by seizures onset. A reverse pattern was observed at the individual level for patients with right TLE. This is the first demonstration of decreased basal functional connectivity within epileptogenic networks with concomitant contralateral increased connectivity possibly reflecting compensatory mechanisms.

Enhanced EEG functional connectivity in mesial temporal lobe epilepsy.

PURPOSE: To analyze and compare spectral properties and interdependencies of intracerebral EEG signals recorded during interictal periods from mesial temporal lobe structures in two groups of epileptic patients defined according to the involvement of these structures in the epileptogenic zone (EZ). METHODS: Interictal EEG activity in mesial temporal lobe (MTL) structures (hippocampus, entorhinal cortex and amygdala) was obtained from intracerebral recordings performed in 21 patients with drug-resistant mesial temporal lobe epilepsy (MTLE group). This group was compared with a "control" group of patients (non-MTLE group) in whom depth-EEG recordings of MTL show that seizures did not start from the MTL. Comparison criteria were based on spectral properties and statistical coupling (nonlinear correlation coefficient h(2)) of MTL signals. RESULTS: Power spectral density analysis showed a significant decrease in the theta frequency sub-band (p=0.01) in the MTLE group. Nonlinear correlation (h(2)) values were found to be higher in the MTLE group than in the NMTLE group (p=0.0014). This effect was significant for theta, alpha, beta and gamma frequencies. Correlation values were not correlated with the frequency of interictal spikes (IS) and significant differences between groups were still measureable even when spikes were suppressed from analyzed EEG periods. DISCUSSION: This study shows that, during the interictal state, the EZ in MTLE is characterized by a decrease of oscillations in the theta sub-band and by a general increase of signal interdependencies. This last finding suggests that the EZ is characterized by network of neuronal assemblies with a reinforced functional connectivity.

Interictal functional connectivity of human epileptic networks assessed by intracerebral EEG and BOLD signal fluctuations.

In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal derived from resting state functional magnetic resonance imaging (fMRI) reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG) and resting-state functional MRI (fMRI) in 5 patients suffering from intractable temporal lobe epilepsy (TLE). Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions) during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband) and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal). This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional connectivity measured by iEEG and BOLD signals give complementary but sometimes inconsistent information in TLE.