Language lateralization in temporal lobe epilepsy using functional MRI and probabilistic tractography

Purpose: Language functional magnetic resonance imaging (fMRI) is used to noninvasively assess hemispheric language specialization as part of the presurgical work-up in temporal lobe epilepsy (TLE). White matter asymmetries on diffusion tensor imaging (DTI) may be related to language specialization as shown in controls and TLE. To refine our understanding of the effect of epilepsy on the structure–function relationships, we focused on the arcuate fasciculus (ArcF) and the inferior occipitofrontal fasciculus (IOF) and tested the relationship between DTI- and fMRI-based lateralization indices in TLE.
Methods: fMRI with three language tasks and DTI were obtained in 20 patients (12 right and 8 left TLE). The ArcF, a major language-related tract, and the IOF were segmented bilaterally using probabilistic tractography to obtain fractional anisotropy (FA) lateralization indices. These were correlated with fMRI-based lateralization indices computed in the inferior frontal gyrus (Pearson's correlation coefficient).
Results: fMRI indices were left-lateralized in 16 patients and bilateral or right-lateralized in four. In the ArcF, FA was higher on the left than on the right side, reaching significance in right but not in left TLE. We found a positive correlation between ArcF anisotropy and fMRI-based lateralization indices in right TLE (p < 0.009), but not in left TLE patients. No correlation was observed for the IOF.
Conclusions: Right TLE patients with more left-lateralized functional activations also showed a leftward-lateralized arcuate fasciculus. The decoupling between the functional and structural indices of the ArcF underlines the complexity of the language network in left TLE patients.     

Functional connectivity homogeneity correlates with duration of temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is often associated with progressive changes to seizures, memory, and mood during its clinical course. However, the cerebral changes related to this progression are not well understood. Because the changes may be related to changes in brain networks, we used functional connectivity MRI (fcMRI) to determine whether brain network parameters relate to the duration of TLE. Graph theory-based analysis of the sites of reported regions of TLE abnormality was performed on resting-state fMRI data in 48 subjects: 24 controls, 13 patients with left TLE, and 11 patients with right TLE. Various network parameters were analyzed including betweenness centrality (BC), clustering coefficient (CC), path length (PL), small-world index (SWI), global efficiency (GE), connectivity strength (CS), and connectivity diversity (CD). These were compared for patients with TLE as a group, compared to controls, and for patients with left and right TLE separately. The association of changes in network parameters with epilepsy duration was also evaluated. We found that CC, CS, and CD decreased in subjects with TLE compared to control subjects. Analyzed according to epilepsy duration, patients with TLE showed a progressive reduction in CD. In conclusion, we found that several network parameters decreased in patients with TLE compared to controls, which suggested reduced connectivity in TLE. Reduction in CD associated with epilepsy duration suggests a homogenization of connections over time in TLE, indicating a reduction of the normal repertoire of stronger and weaker connections to other brain regions.     

Failed surgery for temporal lobe epilepsy: predictors of long-term seizure-free course

OBJECTIVES: To identify prognostic factors which predict the outcome 2 years after TLE surgery in those patients who were not seizure-free at the 6-month postoperative examination. METHODS: We included 86 postoperative TLE patients who had undergone presurgical evaluation, including video-EEG and high-resolution MRI, and who had seizures between the second and sixth postoperative months. RESULTS: 32% of patients were seizure-free in the second postoperative year. We found that normal MRI findings and secondarily generalized seizures (SGTCS) preoperatively were associated with a non-seizure-free outcome, while rare postoperative seizures and ipsilateral temporal IED with seizure-free outcome. Newly administered levetiracetam showed a significant positive effect on the postoperative outcome independent of other prognostic factors. Five of seven patients who received levetiracetam became seizure-free (p = 0.006). CONCLUSION: One-third of patients who did not become seizure-free immediately after surgery, eventually achieved long-term seizure freedom. We suggest watching for long-term seizure freedom after failed epilepsy surgery especially in patients who had rare postoperative seizures, focal MRI abnormality, ipsilateral temporal spikes, or no SGTCS preoperatively. Levetiracetam may have a positive effect on postsurgical seizures.     

Ictal vocalizations occur more often in temporal lobe epilepsy with dominant (left-sided) epileptogenic zone

Objective:   To investigate the lateralization value of ictal vocalizations in temporal lobe epilepsy (TLE).
Methods:   We reviewed video-recordings of 97 patients who had undergone presurgical evaluation programs with video-EEG (electroencephalography)–recorded complex partial seizures (CPS) and high-resolution magnetic resonance imaging (MRI). All patients had surgery due to TLE and became seizure-free. In 57 patients, determination of speech dominance was necessary by using Wada tests or functional MRI (fMRI). To reevaluate the archived seizures, we reviewed one to three consecutively recorded CPS of each patient. Altogether 223 archived seizures were analyzed. Ictal vocalization was considered to be present in a particular patient if it occurred in at least one of the recorded seizures.
Results:   Ictal vocalizations occurred in 22 patients. They occurred in 37% of left-sided and in 11% of right-sided patients with TLE (p = 0.003). In patients with determined speech lateralization, ictal vocalizations occurred in 37% of the dominant and in 14% in patients with nondominant epileptogenic zone (p = 0.04). In patients with ictal vocalizations, epilepsy began at age 8.7 ± 6, whereas in the remaining patients, epilepsy started at age 14.0 ± 9 (p = 0.017). Logistic regression showed that both hemispheric dominance and age at onset were independently associated with pure ictal vocalization (PIV).
Conclusions:   Ictal vocalization is a frequent phenomenon, occurring in 23% of patients with TLE. It is more often associated with left-sided and early onset TLE. Our results may improve the lateralization of the epileptogenic zone and suggest that nonspeech vocalizations in humans are related to the dominant (left-sided) hemisphere. Our study is a further argument that there are different subtypes of TLE depending on the age at onset.     

The impact of hippocampal impairment on task-positive and task-negative language networks in temporal lobe epilepsy

ObjectiveTo study hippocampal integration within task-positive and task-negative language networks and the impact of a diseased left and right hippocampus on the language connectome in temporal lobe epilepsy (TLE).MethodsWe used functional magnetic resonance imaging (fMRI) to study a homogenous group of 32 patients with TLE (17 left) and 14 healthy controls during a verb-generation task. We performed functional connectivity analysis and quantified alterations within the language connectome and evaluated disruptions of the functional dissociation along the anterior-posterior axis of the hippocampi.ResultsConnectivity analysis revealed significant differences between left and right TLE compared to healthy controls. Left TLE showed widespread impairment of task-positive language networks, while right TLE showed less pronounced alterations. Particularly right TLE showed altered connectivity for cortical regions that were part of the default mode network (DMN). Left TLE showed a disturbed functional dissociation pattern along the left hippocampus to left and right inferior frontal language regions, while left and right TLE revealed an altered dissociation pattern along the right hippocampus to regions associated with the DMN.ConclusionsOur results showed an impaired hippocampal integration into active language and the default mode networks, which both may contribute to language impairment in TLE.SignificanceOur results emphasize the direct role of the left hippocampus in language processing, and the potential role of the right hippocampus as a modulator between DMN and task-positive networks.     

Imaging language networks before and after anterior temporal lobe resection: results of a longitudinal fMRI study

Purpose: Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left‐hemisphere–dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks. Methods: We studied 44 patients with TLE due to unilateral hippocampal sclerosis (24 left) on a 3T GE‐MRI scanner. All subjects performed language fMRI and neuropsychological testing preoperatively and again 4 months after left or right ATLR. Key Findings: Postoperatively, individuals with left TLE had greater bilateral middle/inferior frontal fMRI activation and stronger functional connectivity from the left inferior/middle frontal gyri to the contralateral frontal lobe than preoperatively, and this was not observed in individuals with right TLE. Preoperatively, in left and right TLE, better naming correlated with greater preoperative left hippocampal and left frontal activation for verbal fluency (VF). In left TLE, stronger preoperative left middle frontal activation for VF was predictive of greater decline in naming after ATLR. Postoperatively, in left TLE with clinically significant naming decline, greater right middle frontal VF activation correlated with better postoperative naming. In patients without postoperative naming decline, better naming correlated with greater activation in the remaining left posterior hippocampus. In right TLE, naming ability correlated with left hippocampal and left and right frontal VF activation postoperatively. Significance: In left TLE, early postoperative reorganization to the contralateral frontal lobe suggests multiple systems support language function. Postoperatively, ipsilateral recruitment involving the posterior hippocampal remnant is important for maintaining language, and reorganization to the contralateral hemisphere is less effective. Preoperative left middle frontal activation for VF was predictive of naming decline in left TLE after ATLR.     

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.     

Topiramate and its effect on fMRI of language in patients with right or left temporal lobe epilepsy

Topiramate (TPM) is well recognized for its negative effects on cognition, language performance and lateralization results on the intracarotid amobarbital procedure (IAP). But, the effects of TPM on functional MRI (fMRI) of language and the fMRI signals are less clear. Functional MRI is increasingly used for presurgical evaluation of epilepsy patients in place of IAP for language lateralization. Thus, the goal of this study was to assess the effects of TPM on fMRI signals. In this study, we included 8 patients with right temporal lobe epilepsy (RTLE) and 8 with left temporal lobe epilepsy (LTLE) taking TPM (+TPM). Matched to them for age, handedness and side of seizure onset were 8 patients with RTLE and 8 with LTLE not taking TPM (-TPM). Matched for age and handedness to the patients with TLE were 32 healthy controls. The fMRI paradigm involved semantic decision/tone decision task (in-scanner behavioral data were collected). All epilepsy patients received a standard neuropsychological language battery. One sample t-tests were performed within each group to assess task-specific activations. Functional MRI data random-effects analysis was performed to determine significant group activation differences and to assess the effect of TPM dose on task activation. Direct group comparisons of fMRI, language and demographic data between patients with R/L TLE +TPM vs. -TPM and the analysis of the effects of TPM on blood oxygenation level-dependent (BOLD) signal were performed. Groups were matched for age, handedness and, within the R/L TLE groups, for the age of epilepsy onset/duration and the number of AEDs/TPM dose. The in-scanner language performance of patients was worse when compared to healthy controls - all p<0.044. While all groups showed fMRI activation typical for this task, regression analyses comparing L/R TLE +TPM vs. -TPM showed significant fMRI signal differences between groups (increases in left cingulate gyrus and decreases in left superior temporal gyrus in the patients with LTLE +TPM; increases in the right BA 10 and left visual cortex and decreases in the left BA 47 in +TPM RTLE). Further, TPM dose showed positive relationship with activation in the basal ganglia and negative associations with activation in anterior cingulate and posterior visual cortex. Thus, TPM appears to have a different effect on fMRI language distribution in patients with R/L TLE and a dose-dependent effect on fMRI signals. These findings may, in part, explain the negative effects of TPM on cognition and language performance and support the notion that TPM may affect the results of language fMRI lateralization/localization.     

Neural correlates of verbal semantic memory in patients with temporal lobe epilepsy

Functional imaging data suggest that the core network engaged in verbal semantic memory (SM) processing encompasses frontal and temporal lobe structures, with a strong left lateralization in normal right handers. The impact of long term temporal lobe epilepsy (TLE) on this network has only partly been elucidated. We studied verbal SM in 50 patients with chronic, intractable TLE (left TLE=26, right TLE=24) and 35 right handed normal controls using a verbal fMRI semantic decision paradigm. All patients had language lateralized to the left hemisphere, as verified by the intracarotid amobarbital procedure. Within and between group analyses showed remarkable, group-specific activation profiles. The control group activated frontal and temporal areas bilaterally, with a strong left predominance. Left TLE patients showed a shift of activations of left frontal and medial temporal areas to homologous regions in the right hemisphere. Furthermore, left TLE subjects utilized subcortical structures such as the thalamus and putamen to accomplish the verbal SM task. Contrastively, the activation pattern of right TLE patients resembled that of normal controls, but exhibited "hypofrontality" with a shift from frontal to posterior regions in the temporal, parietal and occipital lobe. Our results show that chronic epileptic activity originating from temporal seizure foci is associated with an alteration of neural circuits which support semantic language processing and that side of seizure focus has a specific impact on the resulting activation network. These findings presumably result from morphological changes and from functional reorganization which are both inherent to chronic TLE.     

Resting state functional connectivity of the hippocampus associated with neurocognitive function in left temporal lobe epilepsy

The majority of patients with temporal lobe epilepsy (TLE) experience disturbances of episodic memory from structural damage or dysfunction of the hippocampus. The objective of this study was to use functional Magnetic Resonance Imaging (fMRI) to identify regions where resting state connectivity to the left hippocampus (LH) is correlated with neuropsychological measures of verbal memory retention in TLE patients. Eleven left TLE (LTLE) patients and 15 control subjects participated in resting state fMRI scans. All LTLE patients underwent neuropsychological testing. Resting state functional connectivity maps to the LH were calculated for each patient, and subsequently used in a multiple regression analysis with verbal memory retention scores as a covariate. The analysis identified brain regions whose connectivity to the LH was linearly related to memory retention scores across the group of patients. In LTLE patients, right sided (contralateral) clusters in the precuneus and inferior parietal lobule (IPL) exhibited increased connectivity to the LH with increased memory retention score; left sided (ipsilateral) regions in the precuneus and IPL showed increased connectivity to the LH with decreased retention score. Patients with high memory retention scores had greater connectivity between the LH–right parietal clusters than between the LH–left parietal clusters; in contrast, control subjects had significantly and consistently greater LH–left hemisphere than LH–right hemisphere connectivity. Our results suggest that increased connectivity in contralateral hippocampal functional pathways within the episodic verbal memory network represents a strengthening of alternative pathways in LTLE patients with strong verbal memory retention abilities. Hum Brain Mapp 35:735–744, 2014. © 2012 Wiley Periodicals, Inc.     

Structural and functional asymmetry of medial temporal subregions in unilateral temporal lobe epilepsy: A 7T MRI study

Mesial temporal lobe epilepsy (TLE) is a common neurological disorder affecting the hippocampus and surrounding medial temporal lobe (MTL). Although prior studies have analyzed whole‐brain network distortions in TLE patients, the functional network architecture of the MTL at the subregion level has not been examined. In this study, we utilized high‐resolution 7T T2‐weighted magnetic resonance imaging (MRI) and resting‐state BOLD‐fMRI to characterize volumetric asymmetry and functional network asymmetry of MTL subregions in unilateral medically refractory TLE patients and healthy controls. We subdivided the TLE group into mesial temporal sclerosis patients (TLE‐MTS) and MRI‐negative nonlesional patients (TLE‐NL). Using an automated multi‐atlas segmentation pipeline, we delineated 10 MTL subregions per hemisphere for each subject. We found significantly different patterns of volumetric asymmetry between the two groups, with TLE‐MTS exhibiting volumetric asymmetry corresponding to decreased volumes ipsilaterally in all hippocampal subfields, and TLE‐NL exhibiting no significant volumetric asymmetries other than a mild decrease in whole‐hippocampal volume ipsilaterally. We also found significantly different patterns of functional network asymmetry in the CA1 subfield and whole hippocampus, with TLE‐NL patients exhibiting asymmetry corresponding to increased connectivity ipsilaterally and TLE‐MTS patients exhibiting asymmetry corresponding to decreased connectivity ipsilaterally. Our findings provide initial evidence that functional neuroimaging‐based network properties within the MTL can distinguish between TLE subtypes. High‐resolution MRI has potential to improve localization of underlying brain network disruptions in TLE patients who are candidates for surgical resection.     

Reorganization of verbal and nonverbal memory in temporal lobe epilepsy due to unilateral hippocampal sclerosis

PURPOSE: Patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) often suffer from material-specific memory impairments. The purpose of this study was to use functional magnetic resonance imaging (fMRI) to study the organization of specific memory functions in these patients. METHODS: We report 14 patients with unilateral TLE and HS, and 10 controls, performing an fMRI memory paradigm of word, picture, and face encoding. RESULTS: Compared with controls, patients with left TLE demonstrated less left MTL and greater right MTL activation and patients with right TLE demonstrated less right MTL and greater left MTL activation. Correlations between fMRI activation and memory performance revealed greater activation in the damaged left hippocampus to be correlated with better verbal memory performance in left TLE patients and greater right hippocampal activation to be correlated with better nonverbal memory in right TLE patients. Conversely, greater fMRI activation in the contralateral hippocampus correlated with worse memory performance. CONCLUSIONS: Our findings suggest that memory function in unilateral TLE is better when it is sustained by activation within the damaged hippocampus and that reorganization to the undamaged MTL is an inefficient process, incapable of preserving memory function.     

Neural correlates of verbal semantic memory in patients with temporal lobe epilepsy

Functional imaging data suggest that the core network engaged in verbal semantic memory (SM) processing encompasses frontal and temporal lobe structures, with a strong left lateralization in normal right handers. The impact of long term temporal lobe epilepsy (TLE) on this network has only partly been elucidated. We studied verbal SM in 50 patients with chronic, intractable TLE (left TLE = 26, right TLE = 24) and 35 right handed normal controls using a verbal fMRI semantic decision paradigm. All patients had language lateralized to the left hemisphere, as verified by the intracarotid amobarbital procedure. Within and between group analyses showed remarkable, group-specific activation profiles. The control group activated frontal and temporal areas bilaterally, with a strong left predominance. Left TLE patients showed a shift of activations of left frontal and medial temporal areas to homologous regions in the right hemisphere. Furthermore, left TLE subjects utilized subcortical structures such as the thalamus and putamen to accomplish the verbal SM task. Contrastively, the activation pattern of right TLE patients resembled that of normal controls, but exhibited ‘hypofrontality’ with a shift from frontal to posterior regions in the temporal, parietal and occipital lobe. Our results show that chronic epileptic activity originating from temporal seizure foci is associated with an alteration of neural circuits which support semantic language processing and that side of seizure focus has a specific impact on the resulting activation network. These findings presumably result from morphological changes and from functional reorganization which are both inherent to chronic TLE.     

Lesion patterns and mechanism of cerebral infarction caused by severe atherosclerotic intracranial internal carotid artery stenosis

The hippocampus is believed to have close relationship with many cerebral cortexes and constitute memory network to modulate and facilitate communication, which makes it especially interesting and meaningful in the study of functional connectivity in mild cognitive impairment (MCI). However, functional connectivity between the hippocampus and other brain regions remains unclear in MCI. Furthermore, the longitudinal changes of the hippocampal connectivity have not been reported. In the study, resting state functional MRI (fMRI) was used to examine changes in hippocampal connectivity comparing 14 patients and 14 healthy age-matched controls. We found that functional connectivity between the hippocampus and a set of regions was disrupted in MCI, these regions are: the right frontal lobe, the bilateral temporal lobe and the right insular. While, the left posterior cingulate cortex, precuneus, hippocampus, caudate and right occipital gyrus showed increased connectivity to the hippocampus in MCI. Additionally, we traced the seven MCI patients and compared the hippocampal connectivity in initial stage and 3 years later stage. Several regions presented decreased connectivity to the hippocampus after 3 years. Finally, the hippocampal connectivity with some regions showed significant correlation with the cognitive performance of patients. Based on these findings, the decreased hippocampal connectivity might indicate reduced integrity of hippocampal cortical memory network in MCI. In addition, the increased hippocampal connectivity suggested compensation for the loss of memory function. With the development of the disease, the hippocampal connectivity may lose some compensation and add some more disruption due to the pathological changes.     

Advantages of sentence-level fMRI language tasks in presurgical language mapping for temporal lobe epilepsy

fMRI language mapping has become increasingly utilized for determining language dominance before surgical intervention for temporal lobe epilepsy (TLE). This study aimed to examine the differences between two classes of fMRI word generation tasks used in our clinic: tasks using a single word cue, referred to as simple generative tasks (SGTs), and tasks also involving sentence-level processing, referred to as sentence-level language tasks (SLTs). Specifically, we aimed to investigate the extent and laterality of activation and frontal–temporal connectivity during these language tasks and their relationship to clinical language measures. Thirty-one patients with TLE (18 patients with left TLE and 13 patients with right TLE) performed four language tasks during an fMRI scan, two SGTs and two SLTs. We found significantly greater activity for SLTs over SGTs in bilateral inferior frontal and middle temporal gyri and the left temporal pole. Sentence-level language tasks also showed greater lateralization compared with SGTs. Finally, we found that while activation extent did not correlate with clinical language tests, the degree of left frontal–temporal connectivity was significantly correlated with naming and semantic fluency performance. These correlations also were more robust for SLTs than for SGTs. Taken together, these results provide a compelling argument for including some form of SLTs in fMRI language lateralization protocols for TLE as they allow for better characterization of language networks, particularly in the temporal lobes which are at risk in surgery.     

Cross hippocampal influence in mesial temporal lobe epilepsy measured with high temporal resolution functional magnetic resonance imaging

Purpose Mesial temporal lobe epilepsy (mTLE) is a chronic disorder with spontaneous seizures recurring for years, or even decades. Many structural and functional changes have been detected in both the seizure focus and distal regions throughout the brain over this duration that may reflect the development of epileptogenic networks. Resting state functional magnetic resonance imaging (fMRI) connectivity mapping has the potential to elucidate and quantify these networks. The network between the left and right hippocampus may very likely be one of the most susceptible to changes due to long‐term seizure propagation effects. Therefore, the objective of this study was to quantify cross hippocampal influence in mTLE using high temporal resolution fMRI, and to determine its relationship with disease duration. Methods fMRI images were acquired in the resting (interictal) state with 500 ms temporal resolution across the temporal lobes of 19 mTLE patients (13 left, 6 right). The left and right hippocampi were identified on each subject’s images using both structurally defined and functionally defined boundaries. The cross hippocampal influence was quantified in two ways for each pair of regions: (1) the nondirectional hippocampal functional connectivity calculated as the Pearson’s correlation between the average time series in the left and the right hippocampus regions, and (2) the Granger causality (GC) laterality measure, which implies directional influence by determining temporal precedence. Each of these measures was correlated with age, age of onset, and disease duration across subjects to investigate relationship to disease progression. Key Findings The hippocampal connectivity was not significantly different between patients with left and right mTLE using either the structurally or the functionally defined regions. Across all patients, hippocampal connectivity was not correlated significantly with age of onset or duration of disease. However, as duration of disease increased after 10 years (nine patients), the hippocampal connectivity increased linearly. Using the functionally defined regions, the GC laterality was increased in the right mTLE over the left mTLE, indicating that the left hippocampus was influencing the right hippocampus more than the right influencing left. This was also positively correlated with age of onset. Furthermore, like hippocampal connectivity, the relationship between GC laterality and duration of disease changes after 10 years duration of disease. After this duration, the GC laterality was positive in the three of three patients with right mTLE (left influencing right), whereas the GC laterality was negative in five of six patients with left mTLE (right influencing left). Significance This study reveals a relationship between fMRI functional connectivity and causal influence of the left and right hippocampi and duration of disease in mTLE. During the interictal state, the interhemispheric hippocampal connectivity initially is disrupted and then linearly increases as the epilepsy progresses longer than 10 years. This increase in connectivity appears to be due to the hippocampus contralateral to the epileptogenic focus exerting more influence over the ipsilateral hippocampus. These findings may have implications in understanding the functional development of epileptic networks and possibly prediction of surgical outcome of mTLE.     

Language lateralization in temporal lobe epilepsy: a comparison between fMRI and the Wada Test

PURPOSE: Recent studies have claimed that language functional magnetic resonance imaging (fMRI) can identify language lateralization in patients with temporal lobe epilepsy (TLE) and that fMRI-based findings are highly concordant with the conventional assessment procedure of speech dominance, the intracarotid amobarbital test (IAT). METHODS: To establish the power of language fMRI to detect language lateralization during presurgical assessment, we compared the findings of a semantic decision paradigm with the results of a standard IAT in 68 patients with chronic intractable right and left temporal lobe epilepsy (rTLE, n=28; lTLE, n=40) who consecutively underwent a presurgical evaluation program. The patient group also included 14 (20.6%) subjects with atypical (bilateral or right hemisphere) speech. Four raters used a visual analysis procedure to determine the laterality of speech-related activation individually for each patient. RESULTS: Overall congruence between fMRI-based laterality and the laterality quotient of the IAT was 89.3% in rTLE and 72.5% in lTLE patients. Concordance was best in rTLE patients with left speech. In lTLE patients, language fMRI identified atypical, right hemisphere speech dominance in every case, but missed left hemisphere speech dominance in 17.2%. Frontal activations had higher concordance with the IAT than did activations in temporoparietal or combined regions of interest (ROIs). Because of methodologic problems, recognition of bilateral speech was difficult. CONCLUSIONS: These data provide evidence that language fMRI as used in the present study has limited correlation with the IAT, especially in patients with lTLE and with mixed speech dominance. Further refinements regarding the paradigms and analysis procedures will be needed to improve the contribution of language fMRI for presurgical assessment.     

Hypersalivation in temporal lobe epilepsy

PURPOSE: We sought to determine whether hypersalivation helps lateralize seizure onset during complex partial seizures of temporal lobe origin. Several clinical signs, which help lateralize seizure onset, have been reported in temporal lobe epilepsy (TLE). Increased salivation only occasionally has been reported as a manifestation of partial epilepsy. METHODS: Of 590 consecutive patients admitted for video-EEG monitoring, either as a part of a presurgical evaluation of medically intractable epilepsy or for diagnosis and clarification of their paroxysmal symptoms, we identified 10 patients with ictal hypersalivation as a prominent manifestation of complex partial seizures. We reviewed the clinical features, scalp-sphenoidal video-EEG monitoring, intracarotid amytal (Wada) testing, hippocampal volumetric magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (FDG-PET) scans of these patients. RESULTS: Of the 10 patients with ictal hypersalivation, seven patients had nondominant/right TLE, and three patients had dominant/left TLE. All patients had hippocampal atrophy on volumetric MRI. Eight of the 10 patients underwent standard temporal lobectomy with amygdalohippocampectomy (six right, two left). All of the operated-on patients had a seizure-free (Engel class I) outcome, and their increased salivation resolved. Two patients, who did not undergo surgical treatment, continue to have complex partial seizures with increased salivation. CONCLUSIONS: We conclude that increased salivation as a prominent ictal finding in complex partial seizures of temporal lobe origin is more likely to be of nondominant temporal lobe origin. Further studies with larger numbers of patients are needed to replicate this finding.     

Functional connectivity networks are disrupted in left temporal lobe epilepsy

OBJECTIVE: Functional connectivity maps the distributed network of brain regions fluctuating synchronously during a continuous brain state. This study sought to investigate whether patients with left temporal lobe epilepsy (TLE) differ from controls in their resting-state functional connectivity between typical language regions. METHODS: We studied 17 patients with left TLE, together with eight healthy controls, using seeded functional connectivity. Seed regions were defined using the regions of maximal activation and deactivation during a language functional magnetic resonance imaging (fMRI) task in a separate cohort of 30 controls. RESULTS: Language fMRI produced the expected activation pattern, which was not different between patients and controls. However, functional connectivity between language areas during rest was markedly different; whereas controls showed connectivity between each of the seed areas and the majority of the language areas, patients showed connectivity only with a few areas, particularly the seed area itself. This difference was significant in the direct comparison of patients and control connectivity maps. INTERPRETATION: We suggest that this reduced connectivity in left temporal lobe epilepsy may reflect a disturbance of the language network during resting state in patients and may be related to subtle language difficulties in this patient population.     

Resting‐state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post‐surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting‐state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting‐state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left‐hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations. Hum Brain Mapp, 36:288–303, 2015. © 2014 Wiley Periodicals, Inc.