Left mTLE Patients Research Articles

Studyof the microstructure of brain white matter in medial temporal lobe epilepsy based on diffusion tensor imaging.

To compare the white matter (WM) asymmetry in left and right medial temporal lobe epilepsy (mTLE) with and without hippocampal sclerosis (HS+, HS-) and assess the correlation of preoperative asymmetry and the dynamics of WM fibers with surgical outcomes. Preoperative MRI scans were collected from 58 mTLE patients (40 HS+, 18 HS-); 15 (11 HS+, 4 HS-) then underwent postoperative MRI scans. DTI parameters, including the fractional anisotropy (FA), mean diffusion coefficient (MD), axial diffusion coefficient (AD), and radial diffusion coefficient (RD), were extracted from 20 paired WM tracts by PANDA based on the JHU WM tractography atlas. The bilateral cerebral parameters and the pre- to postoperative changes in the DTI parameters of specific fiber tracts were compared. The asymmetry indexes (AIs) of paired fibers were also analyzed. There were fewer asymmetrical WM fibers in HS- patients than in HS+ patients. The pattern of WM asymmetry differed between left and right mTLE patients. Differences in the FA AI of the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus (ILF) were found in left HS+ patients with different surgical outcomes. All mTLE patients exhibited decreases in FA and increases in MD and RD in specific ipsilateral WM fibers. In International League Against Epilepsy (ILAE) grade 1 patients, the MD values in the ipsilateral CGH increased over time, whereas the RD values in the ipsilateral ILF and the AD values in the ipsilateral ILF and UNC decreased. In ILAE grade 2-5 patients, the FA values in the ipsilateral cingulate gyrus part of the cingulum (CGC) increased over time. The WM tract asymmetry was more extensive in HS+ patients than in HS- patients. The preoperative WM fiber AIs in left HS+ patients may be useful for surgical prognosis. Additionally, pre- to postoperative changes in WM fibers may help predict surgical outcomes.

Functional connectivity between mesial temporal and default mode structures may help lateralize surgical temporal lobe epilepsy.

The most common surgically treatable epilepsy syndrome is mesial temporal lobe epilepsy (mTLE). Preoperative noninvasive lateralization of mTLE is challenging in part due to rapid contralateral seizure spread. Abnormal connections in both the mesial temporal lobe and resting-state networks have been described in mTLE, but it is unclear if connectivity between these networks may aid in lateralization. In 52 patients with left mTLE (LmTLE) or right mTLE (RmTLE) and 52 matched control subjects, the authors acquired 20 minutes of resting-state functional MRI (fMRI) and evaluated functional connectivity of bilateral hippocampi and amygdalae with selected resting-state networks. They used Pearson correlation, network-based statistic, and dynamic causal modeling. Also, to evaluate the clinical utility of a resting-state connectivity model in lateralizing unilateral presurgical mTLE patients, they used receiver operating characteristic curve analysis. RmTLE patients demonstrated decreased nondirected connectivity between the right hippocampus and default mode network compared with LmTLE patients and control subjects. Network-based statistic analysis revealed that the network with most decreased connectivity that distinguished LmTLE from RmTLE patients included the right hippocampus and amygdala, right lateral orbitofrontal cortices, and bilateral inferior parietal lobules, precuneus, and medial orbitofrontal cortices. Dynamic causal modeling analysis revealed that cross-hemispheric connectivity between hippocampi and amygdalae was predominantly inward toward the epileptogenic side. A regression model incorporating these connectivity patterns was used to accurately lateralize mTLE patients with an area under the receiver operating characteristic curve of 0.87. Evaluating fMRI connectivity between mesial temporal structures and default mode network may aid in mTLE lateralization, reduce need for intracranial monitoring, and guide surgical planning.

336 Connectivity Between Resting-State Networks and Mesial Temporal Regions May Distinguish Between Right and Left Mesial Temporal Lobe Epilepsy

INTRODUCTION: Mesial temporal lobe epilepsy (mTLE) is the most common surgical epilepsy. Confidently lateralizing mTLE preoperatively may be challenging with only noninvasive evaluations. Resting-state fMRI has been used to identify connectivity abnormalities in mTLE, involving mesial temporal structures and other networks such as default mode network (DMN). METHODS: We acquired 20 minutes of resting-state fMRI in 52 mTLE patients (28 females, 39.5 ± 12.2 years) and 52 age/gender matched controls. In mTLE patients versus controls, we evaluated fMRI functional connectivity of bilateral hippocampi/amygdalae and resting-state networks (default mode, central executive, salience, visual) using non-directed Pearson correlation (Z-scored), network-based statistic (NBS), and directed dynamic causal modeling (DCM). We separately acquired 2 minutes of resting-state SEEG in 17 unilateral mTLE patients (10 females, 34.6 ± 12.5 years). Using SEEG, we measured hippocampal versus extrahippocampal inward partial directed coherence (PDC) strength. RESULTS: Right mTLE patients demonstrated reduced undirected functional connectivity (Z) between right hippocampus and DMN compared to left mTLE patients and controls (p < 0.001, corrected, ANOVA). These were not seen between the hippocampus and other resting-state networks. Focusing on mesial temporal and DMN nodes, NBS analysis demonstrated the network with most decreased connectivity in right versus left mTLE included right hippocampus/amygdala, bilateral inferior parietal, precuneus, and medial orbitofrontal, and right lateral orbitofrontal regions (9 of 14 nodes, p = 0.006, corrected). With model exceedance probabilities, DCM analysis revealed cross-hemispheric connectivity between hippocampi/amygdalae was mostly inward to epileptogenic-side. FMRI finding resembled SEEG findings, where inward PDC strength was higher in epileptogenic hippocampi compared to other regions in right/left mTLE (p < 0.05, t-tests, corrected). CONCLUSION: If improved, this may aid surgical planning and reduce need for intracranial monitoring. Inward patterns using fMRI and SEEG appear altered at epileptogenic hippocampi, warranting further comparative study of directional connectivity between fMRI and SEEG.

Distinct patterns of hippocampal subfield volume loss in left and right mesial temporal lobe epilepsy.

To investigate the pattern and severity of hippocampal subfield volume loss in patients with left and right mesial temporal lobe epilepsy (mTLE) using quantitative MRI volumetric analysis. A total of 21 left and 14 right mTLE subjects, as well as 15 healthy controls, were enrolled in this cross-sectional study. A publically available magnetic resonance imaging (MRI) brain volumetry system (volBrain) was used for volumetric analysis of hippocampal subfields. The T1-weighted images were processed with a HIPS pipeline. A distinct pattern of hippocampal subfield atrophy was found between left and right mTLE patients when compared with controls. Patients with left mTLE exhibited ipsilateral hippocampal atrophy and segmental volume depletion of the Cornu Ammonis (CA) 2/CA3, CA4/dentate gyrus (DG), and strata radiatum-lacunosum-moleculare (SR-SL-SM). Those with right mTLE exhibited similar ipsilateral hippocampal atrophy but with additional segmental CA1 volume depletion. More extensive bilateral subfield volume loss was apparent with right mTLE patients. We demonstrate that left and right mTLE patients show a dissimilar pattern of hippocampal subfield atrophy, suggesting the pathophysiology of epileptogenesis in left and right mTLE to be different.

Autobiographical memory in epileptic patients after temporal lobe resection or bitemporal hippocampal sclerosis.

The human hippocampus is believed to be a crucial node in the neural network supporting autobiographical memory retrieval. Structural mesial temporal damage associated with temporal lobe epilepsy (TLE) provides an opportunity to systematically investigate and better understand the local and distal functional consequences of mesial temporal damage in the engagement of the autobiographical memory network. We examined 19 TLE patients (49.21 ± 11.55years; 12 females) with unilateral mesial TLE (MTLE; 12 with anterior temporal lobe resection: 6 right MTLE, 6 left MTLE) or bilateral mesial TLE (7 BMTLE) and 18 matched healthy subjects. We used functional MRI (fMRI) with an adapted autobiographical memory paradigm and a specific neuropsychological test (Autobiographical Memory Interview, AMI). While engaged in the fMRI autobiographical memory paradigm, all groups activated a large fronto-temporo-parietal network. However, while this network was left lateralized for healthy participants and right MTLE patients, left MTLE and patients with BMTLE also showed strong activation in right temporal and frontal regions. Moreover, BMTLE and left MTLE patients also showed significant mild deficits in episodic autobiographical memory performance measured with the AMI test. The right temporal and extra-temporal fMRI activation, along with the impairment in autobiographical memory retrieval found in left MTLE and BMTLE patients suggest that alternate brain areas-other than the hippocampus-may also support this process, possibly due to neuroplastic effects.

White matter microstructural differences between right and left mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (mTLE) is a chronic focal epileptic disorder characterized by recalcitrant seizures often necessitating surgical intervention. Identifying the laterality of seizure focus is crucial for pre-surgical planning. We implemented diffusion MRI (DMRI) connectometry to identify differences in white matter connectivity in patients with left and right mTLE relative to healthy control subjects. We enrolled 12 patients with right mTLE, 12 patients with left mTLE, and 12 age/sex matched healthy controls (HCs). We used DMRI connectometry to identify local connectivity patterns of white matter tracts, based on quantitative anisotropy (QA). We compared QA of white matter to reconstruct tracts with significant difference in connectivity between patients and HCs and then between patients with left and right mTLE. Right mTLE patients show higher anisotropy in left inferior longitudinal fasciculus (ILF) and forceps minor and lower QA in genu of corpus callosum (CC), bilateral corticospinal tracts (CSTs), and bilateral middle cerebellar peduncles (MCPs) compared to HCs. Left mTLE patients show higher anisotropy in genu of CC, bilateral CSTs, and right MCP and decreased anisotropy in forceps minor compared to HCs. Compared to patients with right mTLE, left mTLE patients showed increased and decreased connectivity in some major tracts. Our study showed the pattern of microstructural disintegrity in mTLE patients relative to HCs. We demonstrated that left and right mTLE patients have discrepant alternations in their white matter microstructure. These results may indicate that left and right mTLE have different underlying pathologic mechanisms.

Monaural 40-Hz auditory steady-state magnetic responses can be useful for identifying epileptic focus in mesial temporal lobe epilepsy

ObjectivePatients with mesial temporal lobe epilepsy (mTLE) often exhibit central auditory processing (CAP) dysfunction. Monaural 40-Hz auditory steady-state magnetic responses (ASSRs) were recorded to explore the pathophysiology of mTLE. MethodsEighteen left mTLE patients, 11 right mTLE patients and 16 healthy controls (HCs) were examined. Monaural clicks were presented at a rate of 40 Hz. Phase-locking factor (PLF) and power values were analyzed within bilateral Heschl’s gyri. ResultsMonaural 40-Hz ASSR demonstrated temporal frequency dynamics in both PLF and power data. Symmetrical hemispheric contralaterality was revealed in HCs. However, predominant contralaterality was absent in mTLE patients. Specifically, right mTLE patients exhibited a lack of contralaterality in response to left ear but not right ear stimulation, and vice versa in left mTLE patients. ConclusionThis is the first study to use monaural 40-Hz ASSR with unilateral mTLE patients to clarify the relationship between CAP and epileptic focus. CAP dysfunction was characterized by a lack of contralaterality corresponding to epileptic focus. SignificanceMonaural 40-Hz ASSR can provide useful information for localizing epileptic focus in mTLE patients.

Reorganization of anterior and posterior hippocampal networks associated with memory performance in mesial temporal lobe epilepsy.

To investigate the pattern of functional demarcation of hippocampal network and its relationship with memory performance in mesial temporal lobe epilepsy (mTLE) with unilateral hippocampal sclerosis. Resting state fMRI data were acquired from fifteen left mTLE patients, fourteen right mTLE patients and twenty healthy subjects. We explore the hippocampal-cortical alterations and corresponding inter-hemispheric functional connectivity (FC) across anterior and posterior hippocampal networks. The association between FC and memory performance was assessed. Left mTLE showed increased intra-hemispheric FC in anterior hippocampal networks, including left anterior hippocampal-entorhinal cortex and right anterior hippocampal-orbitofrontal cortex, and decreased inter-hemispheric FC between anterior hippocampus, entorhinal cortex and posterior cingulate cortex. Right mTLE was associated with extensive reduction in inter-hemispheric FC along the areas of anterior and posterior hippocampal networks. Intra-hemispheric FC between left anterior hippocampus and entorhinal cortex was positively correlated with verbal memory in left mTLE. Inter-hemispheric FC between posterior parahippocampal gyrus was negatively correlated with verbal memory in right mTLE. Our findings suggested that left and right mTLE exhibit different neural reorganization patterns of anterior and posterior hippocampal networks associated with verbal memory. The findings may facilitate the characterization of mTLE associated with memory deficit.

Distinctive Structural and Effective Connectivity Changes of Semantic Cognition Network across Left and Right Mesial Temporal Lobe Epilepsy Patients

Occurrence of language impairment in mesial temporal lobe epilepsy (mTLE) patients is common and left mTLE patients always exhibit a primary problem with access to names. To explore different neuropsychological profiles between left and right mTLE patients, the study investigated both structural and effective functional connectivity changes within the semantic cognition network between these two groups and those from normal controls. We found that gray matter atrophy of left mTLE patients was more severe than that of right mTLE patients in the whole brain and especially within the semantic cognition network in their contralateral hemisphere. It suggested that seizure attacks were rather targeted than random for patients with hippocampal sclerosis (HS) in the dominant hemisphere. Functional connectivity analysis during resting state fMRI revealed that subregions of the anterior temporal lobe (ATL) in the left HS patients were no longer effectively connected. Further, we found that, unlike in right HS patients, increased causal linking between ipsilateral regions in the left HS epilepsy patients cannot make up for their decreased contralateral interaction. It suggested that weakened contralateral connection and disrupted effective interaction between subregions of the unitary, transmodal hub of the ATL may be the primary cause of anomia in the left HS patients.

Functional and structural correlates of memory in patients with mesial temporal lobe epilepsy.

Individuals with medial temporal lobe epilepsy (mTLE) often show material-specific memory impairment (verbal for left, visuospatial for right hemisphere), which can be exacerbated following surgery aimed at the epileptogenic regions of medial and anterolateral temporal cortex. There is a growing body of evidence suggesting that characterization of structural and functional integrity of these regions using MRI can aid in prediction of post-surgical risk of further memory decline. We investigated the nature of the relationship between structural and functional indices of hippocampal integrity with pre-operative memory performance in a group of 26 patients with unilateral mTLE. Structural integrity was assessed using hippocampal volumes, while functional integrity was assessed using hippocampal activation during the encoding of novel scenes. We quantified structural and functional integrity in terms of asymmetry, calculated as (L − R)/(L + R). Factor scores for verbal and visual memory were calculated from a clinical database and an asymmetry score (verbal − visual) was used to characterize memory performance. We found, as expected, a significant difference between left and right mTLE (RTLE) groups for hippocampal volume asymmetry, with each group showing an asymmetry favoring the unaffected temporal lobe. Encoding activation asymmetry showed a similar pattern, with left mTLE patients showing activation preferential to the right hemisphere and RTLE patients showing the reverse. Finally, we demonstrated that functional integrity mediated the relationship between structural integrity and memory performance for memory asymmetry, suggesting that even if structural changes are evident, ultimately it is the functional integrity of the tissue that most closely explains behavioral performance.

Mesial temporal lobe epilepsy with hippocampal sclerosis is a network disorder with altered cortical hubs.

Electrophysiologic hubs within the large-scale functional networks in mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) have not been investigated. We hypothesized that mTLE with HS has different resting-state network hubs in their large-scale functional networks compared to the hubs in healthy controls (HC). We also hypothesized that the hippocampus would be a functional hub in mTLE patients with HS. Resting-state functional networks, identified by using magnetoencephalography (MEG) signals in the theta, alpha, beta, and gamma frequency bands, were evaluated. Networks in 44 mTLE patients with HS (left mTLE = 22; right mTLE = 22) were compared with those in 46 age-matched HC. We investigated betweenness centrality at the source-level MEG network. The main network hubs were at the pole of the left superior temporal gyrus in the beta band, the pole of the left middle temporal gyrus in the beta and gamma bands, left hippocampus in the theta and alpha bands, and right posterior cingulate gyrus in all four frequency bands in mTLE patients; all of which were different from the main network hubs in HC. Only patients with left mTLE showed profound differences from HC at the left hippocampus in the alpha band. Our analysis of resting-state MEG signals shows that altered electrophysiologic functional hubs in mTLE patients reflect pathophysiologic brain network reorganization. Because we detected network hubs in both hippocampal and extrahippocampal areas, it is probable that mTLE is a large-scale network disorder rather than a focal disorder. The hippocampus was a network hub in left mTLE but not in right mTLE patients, which may be due to intrinsic functional and structural asymmetries between left and right mTLE patients. The evaluation of cortical hubs, even in the spike-free resting-state, could be a clinical diagnostic marker of mTLE with HS.

Multivariate pattern analysis reveals anatomical connectivity differences between the left and right mesial temporal lobe epilepsy.

Previous studies have demonstrated differences of clinical signs and functional brain network organizations between the left and right mesial temporal lobe epilepsy (mTLE), but the anatomical connectivity differences underlying functional variance between the left and right mTLE remain uncharacterized. We examined 43 (22 left, 21 right) mTLE patients with hippocampal sclerosis and 39 healthy controls using diffusion tensor imaging. After the whole-brain anatomical networks were constructed for each subject, multivariate pattern analysis was applied to classify the left mTLE from the right mTLE and extract the anatomical connectivity differences between the left and right mTLE patients. The classification results reveal 93.0% accuracy for the left mTLE versus the right mTLE, 93.4% accuracy for the left mTLE versus controls and 90.0% accuracy for the right mTLE versus controls. Compared with the right mTLE, the left mTLE exhibited a different connectivity pattern in the cortical-limbic network and cerebellum. The majority of the most discriminating anatomical connections were located within or across the cortical-limbic network and cerebellum, thereby indicating that these disease-related anatomical network alterations may give rise to a portion of the complex of emotional and memory deficit between the left and right mTLE. Moreover, the orbitofrontal gyrus, cingulate cortex, hippocampus and parahippocampal gyrus, which exhibit high discriminative power in classification, may play critical roles in the pathophysiology of mTLE. The current study demonstrated that anatomical connectivity differences between the left mTLE and the right mTLE may have the potential to serve as a neuroimaging biomarker to guide personalized diagnosis of the left and right mTLE.

Disrupted topological properties of brain white matter networks in left temporal lobe epilepsy: A diffusion tensor imaging study

Mesial temporal lobe epilepsy (mTLE) is the most common drug-refractory focal epilepsy in adults. Although previous functional and morphological studies have revealed abnormalities in the brain networks of mTLE, the topological organization of the brain white matter (WM) networks in mTLE patients is still ambiguous. In this study, we constructed brain WM networks for 14 left mTLE patients and 22 age- and gender-matched normal controls using diffusion tensor tractography and estimated the alterations of network properties in the mTLE brain networks using graph theoretical analysis. We found that networks for both the mTLE patients and the controls exhibited prominent small-world properties, suggesting a balanced topology of integration and segregation. However, the brain WM networks of mTLE patients showed a significant increased characteristic path length but significant decreased global efficiency, which indicate a disruption in the organization of the brain WM networks in mTLE patients. Moreover, we found significant between-group differences in the nodal properties in several brain regions, such as the left superior temporal gyrus, left hippocampus, the right occipital and right temporal cortices. The robustness analysis showed that the results were likely to be consistent for the networks constructed with different definitions of node and edge weight. Taken together, our findings may suggest an adverse effect of epileptic seizures on the organization of large-scale brain WM networks in mTLE patients.

Decreased white matter integrity in mesial temporal lobe epilepsy: a machine learning approach.

Statistical analysis on diffusion tensor imaging has been used extensively in mesial temporal lobe epilepsy (mTLE) and most studies report decrease in fractional anisotropy (FA) in multiple white matter regions. However, these findings vary across studies and between regions. Therefore, in this study, we used tract-based spatial statistics along with machine learning approaches to investigate the whole-brain white matter changes between 17 left mTLE patients and 15 right mTLE patients and 34 matched healthy controls. The results showed that the three groups could be distinguished from each other with promising accuracy. Compared with controls, the FA value of the most discriminating voxels was decreased in the ipsilateral limbic system, corpus callosum, and temporal white matter in both patient groups. Compared with right mTLE, left mTLE had decreased FA in the left temporal white matter, whereas right mTLE had decreased FA in the right frontal and temporal white matter, and right posterior corona radiata. These findings not only provide useful information for lateralization of the seizure focus but can also be used as a potential biomarker for the diagnosis and treatment of the mTLE. This may be helpful in assessment of patients with mTLE when no lesion is detected on visual evaluation.

Usefulness of Wada test in predicting seizure outcome following anterior temporal lobectomy

To study the usefulness of the Wada test for predicting seizure outcome following anterior temporal lobectomy (ATL). From 1996 to 2002, all patients with left mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) and selected patients with right MTLE-HS underwent the Wada test before ATL at our center. Patients were selected for ATL on the basis of unilateral HS on MRI and concordant electro-clinical data. Twelve-item recognition paradigm was used for Wada memory testing. Score of +1 was awarded for a correct response and -0.5 for an incorrect response. We defined Wada failure as a contralateral score of <5, ipsilateral score of >8, and difference score of <0. No patient was denied surgery based on the Wada results. Means of the three scores were compared between seizure free and non-seizure free patients. Sensitivity, specificity and receiver operator characteristic curves of various scores for predicting seizure outcome were calculated. 151 patients (129 left MTLE; mean age: 27.80±8.72 years) formed the study group. At mean postoperative follow-up of 6.4±2.0 years, 127 patients were seizure free. Mean contralateral score was lower in the seizure-free group (7.15±3.07 vs. 8.71±4.13; p<0.001) while ipsilateral and difference scores were similar between the two seizure outcome groups. Areas under the curves for contralateral, ipsilateral and difference scores for predicting seizure-free outcome were 0.49, 0.58 and 0.59, respectively, suggesting its modest usefulness in individual patients. Results remained same when the analysis was restricted to left MTLE patients. Wada test has limited usefulness for predicting seizure outcome following ATL.

Network reconfiguration and working memory impairment in mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (mTLE) is the most prevalent form of focal epilepsy, and hippocampal sclerosis (HS) is considered the most frequent associated pathological finding. Recent connectivity studies have shown that abnormalities, either structural or functional, are not confined to the affected hippocampus, but can be found in other connected structures within the same hemisphere, or even in the contralesional hemisphere. Despite the role of hippocampus in memory functions, most of these studies have explored network properties at resting state, and in some cases compared connectivity values with neuropsychological memory scores. Here, we measured magnetoencephalographic responses during verbal working memory (WM) encoding in left mTLE patients and controls, and compared their effective connectivity within a frontotemporal network using dynamic causal modelling. Bayesian model comparison indicated that the best model included bilateral, forward and backward connections, linking inferior temporal cortex (ITC), inferior frontal cortex (IFC), and the medial temporal lobe (MTL). Test for differences in effective connectivity revealed that patients exhibited decreased ipsilesional MTL-ITC backward connectivity, and increased bidirectional IFC-MTL connectivity in the contralesional hemisphere. Critically, a negative correlation was observed between these changes in patients, with decreases in ipsilesional coupling among temporal sources associated with increases contralesional frontotemporal interactions. Furthermore, contralesional frontotemporal interactions were inversely related to task performance and level of education. The results demonstrate that unilateral sclerosis induced local and remote changes in the dynamic organization of a distributed network supporting verbal WM. Crucially, pre-(peri) morbid factors (educational level) were reflected in both cognitive performance and (putative) compensatory changes in physiological coupling.

Network Alterations Supporting Word Retrieval in Patients with Medial Temporal Lobe Epilepsy

Although the hippocampus is not considered a key structure in semantic memory, patients with medial-temporal lobe epilepsy (mTLE) have deficits in semantic access on some word retrieval tasks. We hypothesized that these deficits reflect the negative impact of focal epilepsy on remote cerebral structures. Thus, we expected that the networks that support word retrieval tasks would be altered in left mTLE patients. We measured brain activity with fMRI while participants (13 controls, 13 left mTLE, and 13 right mTLE) performed a verb generation task. We examined functional connectivity during this task in relation to language performance on an off-line clinical test of lexical access (Boston Naming Test, BNT). Using task-seed-behavior partial least squares, we identified a canonical language network that was more active during verb generation than the baseline condition, but this network did not correlate with variability in BNT performance in either controls or patients. Instead, additional networks were identified for each group, with more anterior temporal and prefrontal regions recruited for controls and more posterior temporal regions for both left and right mTLE patients. Our findings go beyond the literature emphasizing differences in laterality of language processes in mTLE patients and, critically, highlight how network changes can be used to account for performance variation among patients on clinically relevant measures. This strategy of correlating network changes and off-line behavior may provide a powerful tool for predicting a postoperative decline in language performance.

FMRI study of mesial temporal lobe epilepsy using amplitude of low‐frequency fluctuation analysis

Various functional imaging tools have been used to detect epileptic activity in the neural network underlying mesial temporal lobe epilepsy (mTLE). In the present fMRI study, a data-driven approach was employed to map interictal epileptic activity in mTLE patients by measuring the amplitude of low-frequency fluctuation (ALFF) of the blood oxygen level-dependent (BOLD) signal. Twenty-four left mTLE patients and 26 right mTLE patients were investigated by comparing with 25 healthy subjects. In the patients, the regions showing increased ALFF were consistently distributed in the mesial temporal lobe, thalamus, and a few of other cortical and subcortical structures composing a mesial temporal epilepsy network proposed previously, while the regions showing decreased ALFF were mostly located in the areas of so-called default-mode network. Data of simultaneous EEG-fMRI from a portion of the patients suggested that the increases in ALFF might be associated with the interictal epileptic activity. Individual analyses based on statistic parametric mapping revealed a moderate sensitivity and a fairly high specificity for the lateralization of unilateral mTLE. We conclude that the ALFF analysis may provide a useful tool in fMRI study of epilepsy.

Altered spontaneous neuronal activity of the default-mode network in mesial temporal lobe epilepsy

Increasing evidence from behavioral and neuroimaging studies suggests that mesial temporal lobe epilepsy (mTLE) is possibly associated with the default-mode brain function. However, the alteration of coherent neural activities in such a default-mode network (DMN) in mTLE has yet to be investigated. The present study analyzed the resting-state functional MRI data from two groups of mTLE patients with left and right hippocampal sclerosis using independent component analysis. In comparison with healthy controls, decreased functional connectivity in the dorsal mesial prefrontal cortex, mesial temporal lobe and inferior temporal cortex was observed in these two patient groups. Moreover, the right but not left mTLE patients showed bilaterally decreased functional connectivity in the mesial temporal lobe and increased functional connectivity in the posterior cingulate cortex. The decreased functional connectivity of the mesial temporal lobe was related to the epilepsy duration, suggesting that the posterior cingulate cortex may play a compensatory role for the altered DMN in the right mTLE. These findings indicate that the DMN is widely affected even if a single network node is impaired. An extensive regional overlap between the DMN and the previously described epileptic network suggests that the widespread functional impairments in mTLE may attribute to an aberrant DMN. The distinct patterns of the DMN between the left and right mTLE support a view that there are different pathological mechanisms underlying these two types of epilepsies.

Functional Reorganization Associated with Semantic Language Processing in Temporal Lobe Epilepsy Patients after Anterior Temporal Lobectomy : A Longitudinal Functional Magnetic Resonance Image Study

The focus of this study is brain plasticity associated with semantic aspects of language function in patients with medial temporal lobe epilepsy (mTLE). Using longitudinal functional magnetic resonance imaging (fMRI), patterns of brain activation were observed in twelve left and seven right unilateral mTLE patients during a word-generation task relative to a pseudo-word reading task before and after anterior temporal section surgery. No differences were observed in precentral activations in patients relative to normal controls (n = 12), and surgery did not alter the phonological-associated activations. The two mTLE patient groups showed left inferior prefrontal activations associated with semantic processing (word-generation > pseudo-word reading), as did control subjects. The amount of semantic-associated activation in the left inferior prefrontal region was negatively correlated with epilepsy duration in both patient groups. Following temporal resection, semantic-specific activations in inferior prefrontal region became more bilateral in left mTLE patients, but more left-lateralized in right mTLE patients. The longer the duration of epilepsy in the patients, the larger the increase in the left inferior prefrontal semantic-associated activation after surgery in both patient groups. Semantic activation of the intact hippocampus, which had been negatively correlated with seizure frequency, normalized after the epileptic side was removed. These results indicate alternation of semantic language network related to recruitment of left inferior prefrontal cortex and functional recovery of the hippocampus contralateral to the epileptogenic side, suggesting an intra- and inter-hemispheric reorganization following surgery.