Left Temporal Lobe Epilepsy Patients Research Articles

An exploration of anomia rehabilitation in drug-resistant temporal lobe epilepsy

Around 40% of patients who undergo a left temporal lobe epilepsy (LTLE) surgery suffer from anomia (word-finding difficulties), a condition that negatively impacts quality of life. Despite these observations, language rehabilitation is still understudied in LTLE. We assessed the effect of a four-week rehabilitation on four drug-resistant LTLE patients after their surgery. The anomia rehabilitation was based on cognitive descriptions of word finding deficits in LTLE. Its primary ingredients were psycholinguistic tasks and a psychoeducation approach to help patients cope with daily communication issues. We repeatedly assessed naming skills for trained and untrained words, before and during the therapy using an A-B design with follow-up and replication. Subjective anomia complaint and standardized language assessments were also collected. We demonstrated the effectiveness of the rehabilitation program for trained words despite the persistence of seizures. Furthermore, encouraging results were observed for untrained items. Variable changes in anomia complaint were observed. One patient who conducted the protocol as self-rehabilitation responded similarly to the others, despite the different manner of intervention. These results open promising avenues for helping epileptic patients suffering from anomia. For example, this post-operative program could easily be adapted to be conducted preoperatively.

Investigating the effect of hippocampal sclerosis on parietal memory network.

We aimed to investigate differences in episodic memory networks between patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis and healthy controls, especially with regards to the parietal memory network (PMN), as well as their relation to neuropsychological memory performance after mesial temporal resection. 28 healthy subjects as well as 21 patients with TLE (12 left, 9 right) were investigated using a spatial memory fMRI paradigm, which has been shown to activate the PMN. Regions of interest (ROI) were defined based on the results of the second-level analyses and activations within the predefined ROIs were compared across groups and correlated with postoperative verbal and nonverbal memory scores. Healthy subjects showed activations within regions belonging to the dorsal visual stream and the PMN as well as the bilateral parahippocampal place area, the bilateral frontal eye field, and the bilateral middle frontal gyrus. Comparison between groups revealed that TLE patients activated significantly less in the left middle occipital gyrus and the right precuneus. The activation pattern in left TLE patients showed further reductions, mainly in areas belonging to the dorsal visual stream and the PMN within the left hemisphere. Activations within the left superior parietal lobulus, bilateral inferior parietal lobulus, bilateral middle temporal gyrus, left precuneus, left frontal eye field, and left middle frontal gyrus correlated significantly with postoperative verbal memory scores, and activations within the left superior parietal lobulus, left inferior parietal lobulus, left middle temporal gyrus, and left precuneus correlated significantly with higher performance in postoperative nonverbal memory scores. The PMN is involved in episodic memory encoding. Higher activations in areas belonging to the PMN and the dorsal visual stream, especially within the left hemisphere, before amygdalohippocampectomy may result in higher postoperative memory scores. This study aims to investigate the effects of epilepsy due to hippocampal sclerosis, i.e. scarring in the temporal lobe, on memory networks in the brain. We discovered that especially patients with left-sided hippocampal sclerosis show reduced brain activations in visual areas and memory networks within the left hemisphere of the brain during orientation in space. Importantly, higher activations within these areas may result in better memory after epilepsy surgery.

28 Challenges to Lateralizing Visual Memory Dysfunction in TLE Patients

Objective:Neuropsychological assessment is an essential part of presurgical evaluation for epilepsy patients with refractory temporal lobe epilepsy. Evaluations assist in localizing and lateralizing epileptogenic focal points and identifying possible risks for cognitive decline following surgery. Researchers and clinicians consistently find that verbal memory dysfunction is an accurate indicator of left temporal lobe epilepsy (TLE) through verbal measures such as the CVLT-II. Although visual memory structures are assumed to be in the right (nondominant) hemisphere, visual memory assessments have not been reliable in identifying right TLE. It is hypothesized that assessments to test visual memory are confounded by verbal cueing to assist in visual learning. To account for this, researchers have identified that comparing verbal and visual score asymmetries does accurately differentiate left and right TLE patients. This study aimed to determine if verbalvisual asymmetry using the CVLT-II and BVMT-R accurately identifies left and right TLE relative weaknesses potentially associated with epileptogenic regions.Participants and Methods:As part of a pre-surgical neuropsychological evaluation, 37 well-characterized medically refractory TLE patients (18 right TLE; 19 left TLE) were administered the Brief Visuospatial Memory Test-Revised to evaluate visuospatial memory and the CVLT-II to evaluate verbal memory. A multivariate analysis of variance was used to compare RTLE and LTLE group performances on BVMT-R delay recall subscales, using T-scores. Then memory asymmetry scores were calculated by converting CVLT-II verbal delay memory scores to T-scores and subtracting BVMT-R delayed recall T-score from the verbal memory T-score. An independent samples t-test was used to compare asymmetry scores between the groups.Results:There were no significant differences between patients with RTLE and LTLE for BVMT-R Delay [F(2,34) = 0.11, p = .895]. There was not a significant difference when accounting for verbal-visual asymmetry (t (35) = 0.422, p = 0.675, d = 12.566) between left (M = -2.42, SD = 13.82) and right side (M = -4.17, SD = 11.09).Conclusions:The BVMT-R did not identify nondominant hemisphere dysfunction in this sample of 18 right TLE patients. Because visual memory performance did not inform lateralization, we investigated the usefulness of memory asymmetry. Inconsistent with our hypothesis, verbal-visual memory asymmetry scores did not differentiate RTLE from LTLE in this sample. These findings add to existing findings that the BVMT-R may not be able to identify visuospatial memory dysfunction in epilepsy. Additionally, these data indicate the inability to assess for visuospatial memory even when accounting for verbal abilities in epilepsy patients. Future research should consider alternate visuospatial measures for the evaluation of epilepsy patients.

Leveraging the resting brain to predict memory decline after temporal lobectomy.

Predicting memory morbidity after temporal lobectomy in patients with temporal lobe epilepsy (TLE) relies on indices of preoperative temporal lobe structural and functional integrity. However, epilepsy is increasingly considered a network disorder, and memory a network phenomenon. We assessed the utility of functional network measures to predict postoperative memory changes. Seventy-two adults with TLE (37 left/35 right) underwent preoperative resting-state fMRI and pre- and postoperative neuropsychological assessment. We compared functional connectivity throughout the memory network of each patient to a healthy control template (n=19) to identify differences in global organization. A second metric indicated the degree of integration of the to-be-resected temporal lobe with the rest of the memory network. We included these measures in a linear regression model alongside standard clinical variables as predictors of memory change after surgery. Left TLE patients with more atypical memory networks, and with greater functional integration of the to-be-resected region with the rest of the memory network preoperatively, experienced the greatest decline in verbal memory after surgery. Together, these two measures explained 44% of variance in verbal memory change, outperforming standard clinical and demographic variables. None of the variables examined were associated with visuospatial memory change in patients with right TLE. Resting-state connectivity provides valuable information concerning both the integrity of to-be-resected tissue and functional reserve across memory-relevant regions outside of the to-be-resected tissue. Intrinsic functional connectivity has the potential to be useful for clinical decision-making regarding memory outcomes in left TLE, and more work is needed to identify the factors responsible for differences seen in right TLE.

The asymmetry of glymphatic system dysfunction in patients with temporal lobe epilepsy: A DTI-ALPS study

Background and purposeWhile the occurrence of glymphatic system dysfunction has been observed in temporal lobe epilepsy (TLE), the potential asymmetry of this system has yet to be investigated in the TLE context. We aimed to investigate the glymphatic system function in both hemispheres and to analyze asymmetric features of the glymphatic system in TLE patients using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. Materials and methods43 patients (left TLE (LTLE), n = 20; right TLE (RTLE), n = 23) and 39 healthy controls (HC) were enrolled in this study. The DTI-ALPS index was calculated for the left (left ALPS index) and right (right ALPS index) hemispheres respectively. An asymmetry index (AI) was calculated by AI = (Right − Left)/ [(Right + Left)/2] to represent the asymmetric pattern. Independent two sample t-test, two-sample paired t-test or one-way ANOVA with Bonferroni correction were conducted to compare the differences in ALPS indices and AI among the groups. ResultsBoth left ALPS index (p = 0.040) and right ALPS index (p = 0.001) of RTLE patients were significantly decreased, while only left ALPS index of LTLE patients (p = 0.005) was reduced. Compared to contralateral ALPS index, the ipsilateral ALPS index was significantly decreased in TLE (p = 0.008) and RTLE (p = 0.009) patients. Leftward asymmetry of the glymphatic system was found in HC (p = 0.045) and RTLE (p = 0.009) patients. The LTLE patients presented reduced asymmetric traits when compared to RTLE patients (p = 0.029). ConclusionThe TLE patients exhibited altered ALPS indices, which could be triggered by glymphatic system dysfunction. Altered ALPS indices were more severe in ipsilateral than in the contralateral hemisphere. Moreover, LTLE and RTLE patients exhibited different change patterns of the glymphatic system. In addition, glymphatic system function presented asymmetric patterns in both normal adult brain and RTLE patients.

Imaging visuospatial memory in temporal lobe epilepsy-Results of an fMRI study.

PurposeImpairment of cognitive functions is commonly observed in temporal lobe epilepsy (TLE). The aim of this study was to assess visuospatial memory functions and memory-related networks using an adapted version of Roland’s Hometown Walking (RHWT) functional MRI (fMRI) task in patients with TLE.MethodsWe used fMRI to study activation patterns based on a visuospatial memory paradigm in 32 TLE patients (9 right; 23 left) and also within subgroups of lesional and non-lesional TLE. To test for performance, a correlational analysis of fMRI activation patterns and out-of-scanner neuropsychological visuospatial memory testing was performed. Additionally, we assessed memory-related networks using functional connectivity (FC).ResultsGreater contralateral than ipsilateral mesiotemporal (parahippocampal gyrus/hippocampus) activation was observed in left (n = 23)/right (n = 9) TLE. In lesional left TLE (n = 17), significant activations were seen in right more than left mesiotemporal areas (parahippocampal gyrus), while non-lesional left TLE patients (n = 6) showed significant bilateral (left>right) activations in mesiotemporal structures (parahippocampal gyrus). In left TLE, visuospatial cognitive testing correlated with fMRI activations in left (parahippocampal gyrus) and right mesiotemporal structures (hippocampus), characterized by greater fMRI activation being associated with better memory scores. In right TLE, higher scores in visuospatial memory testing were associated with greater fMRI activations in left and right insular regions. FC patterns of memory-related networks differ in right and left TLE.ConclusionWhile TLE in general leads to asymmetrical mesiotemporal activation, lesion-induced and non-lesional TLE patients reveal different memory fMRI activation patterns. In right TLE, insular regions try to compensate for impaired right mesiotemporal structures during the performance of visuospatial tasks. Underlying functional visuospatial memory networks differ in right and left TLE.

Mapping of Language-and-Memory Networks in Patients With Temporal Lobe Epilepsy by Using the GE2REC Protocol.

Preoperative mapping of language and declarative memory functions in temporal lobe epilepsy (TLE) patients is essential since they frequently encounter deterioration of these functions and show variable degrees of cerebral reorganization. Due to growing evidence on language and declarative memory interdependence at a neural and neuropsychological level, we propose the GE2REC protocol for interactive language-and-memory network (LMN) mapping. GE2REC consists of three inter-related tasks, sentence generation with implicit encoding (GE) and two recollection (2REC) memory tasks: recognition and recall. This protocol has previously been validated in healthy participants, and in this study, we showed that it also maps the LMN in the left TLE (N = 18). Compared to healthy controls (N = 19), left TLE (LTLE) showed widespread inter- and intra-hemispheric reorganization of the LMN through reduced activity of regions engaged in the integration and the coordination of this meta-network. We also illustrated how this protocol could be implemented in clinical practice individually by presenting two case studies of LTLE patients who underwent efficient surgery and became seizure-free but showed different cognitive outcomes. This protocol can be advantageous for clinical practice because it (a) is short and easy to perform; (b) allows brain mapping of essential cognitive functions, even at an individual level; (c) engages language-and-memory interaction allowing to evaluate the integrative processes within the LMN; (d) provides a more comprehensive assessment by including both verbal and visual modalities, as well as various language and memory processes. Based on the available postsurgical data, we presented preliminary results obtained with this protocol in LTLE patients that could potentially inform the clinical practice. This implies the necessity to further validate the potential of GE2REC for neurosurgical planning, along with two directions, guiding resection and describing LMN neuroplasticity at an individual level.

The role of the temporal pole in temporal lobe epilepsy: A diffusion kurtosis imaging study

This study aimed to evaluate the use of diffusion kurtosis imaging (DKI) to detect microstructural abnormalities within the temporal pole (TP) and its temporopolar cortex in temporal lobe epilepsy (TLE) patients. DKI quantitative maps were obtained from fourteen lesional TLE and ten non-lesional TLE patients, along with twenty-three healthy controls. Data collected included mean (MK); radial (RK) and axial kurtosis (AK); mean diffusivity (MD) and axonal water fraction (AWF). Automated fiber quantification (AFQ) was used to quantify DKI measurements along the inferior longitudinal (ILF) and uncinate fasciculus (Unc). ILF and Unc tract profiles were compared between groups and tested for correlation with disease duration. To characterize temporopolar cortex microstructure, DKI maps were sampled at varying depths from superficial white matter (WM) towards the pial surface. Patients were separated according to the temporal lobe ipsilateral to seizure onset and their AFQ results were used as input for statistical analyses. Significant differences were observed between lesional TLE and controls, towards the most temporopolar segment of ILF and Unc proximal to the TP within the ipsilateral temporal lobe in left TLE patients for MK, RK, AWF and MD. No significant changes were observed with DKI maps in the non-lesional TLE group. DKI measurements correlated with disease duration, mostly towards the temporopolar segments of the WM bundles. Stronger differences in MK, RK and AWF within the temporopolar cortex were observed in the lesional TLE and noticeable differences (except for MD) in non-lesional TLE groups compared to controls. This study demonstrates that DKI has potential to detect subtle microstructural alterations within the temporopolar segments of the ILF and Unc and the connected temporopolar cortex in TLE patients including non-lesional TLE subjects. This could aid our understanding of the extrahippocampal areas, more specifically the temporal pole role in seizure generation in TLE and might inform surgical planning, leading to better seizure outcomes.

Disrupted functional connectivity in white matter resting-state networks in unilateral temporal lobe epilepsy.

Unilateral temporal lobe epilepsy (TLE) is the most common type of focal epilepsy characterized by foci in the unilateral temporal lobe grey matters of regions such as the hippocampus. However, it remains unclear how the functional features of white matter are altered in TLE. In the current study, resting-state functional magnetic resonance imaging (fMRI) was performed on 71 left TLE (LTLE) patients, 79 right TLE (RTLE) patients and 47 healthy controls (HC). Clustering analysis was used to identify fourteen white matter networks (WMN). The functional connectivity (FC) was calculated among WMNs and between WMNs and grey matter. Furthermore, the FC laterality of hemispheric WMNs was assessed. First, both patient groups showed decreased FCs among WMNs. Specifically, cerebellar white matter illustrated decreased FCs with the cerebral superficial WMNs, implying a dysfunctional interaction between the cerebellum and the cerebral cortex in TLE. Second, the FCs between WMNs and the ipsilateral hippocampus (grey matter foci) were also reduced in patient groups, which may suggest insufficient functional integration in unilateral TLE. Interestingly, RTLE showed more severe abnormalities of white matter FCs, including links to the bilateral hippocampi and temporal white matter, than LTLE. Taken together, these findings provide functional evidence of white matter abnormalities, extending the understanding of the pathological mechanism of white matter impairments in unilateral TLE.

A-163 Utility of the 7/24 Spatial Recall Test in Temporal Lobe Epilepsy

Abstract Objective To examine the utility of the 7/24 Spatial Recall Test (7/24) in the assessment of temporal lobe epilepsy (TLE) patients who have not undergone surgical resection. We hypothesized that patients with right TLE (RTLE) would perform significantly worse on the 7/24 than patients with left TLE (LTLE), but better on measures of verbal memory and naming. Participants and Methods Twenty-one patients with RTLE and 17 patients with LTLE were identified from a larger dataset of 152 epilepsy patients who underwent comprehensive neuropsychological evaluations at Brigham and Women’s Hospital. Exclusion criteria included: 1) Extratemporal, bitemporal, or unclear seizure onset, 2) Post-surgical evaluations, and 3) Co-morbid neurodegenerative or neurological conditions. The Rey Auditory Verbal Learning Test (RVLT) and Boston Naming Test (BNT) and were selected as outcome measures of verbal memory and naming, respectively. Results Independent samples t-tests revealed that patients with RTLE performed significantly worse on the 7/24 delayed recall than LTLE patients (p = 0.026), but there were no significant differences between groups in their 7/24 immediate recall across trials (p = 0.118). As predicted, patients with LTLE performed significantly worse than RTLE patients on the BNT (p = 0.005), however no significant differences were found between groups on the RVLT total learning, short delay, or long delay. Conclusions These findings support the use of the 7/24 for assessing nonverbal memory in patients with TLE, and more specifically, suggest that the 7/24 may be a sensitive measure for detecting lateralized dysfunction of the right temporal lobe in TLE patients.

Accurate lateralization and classification of MRI-negative 18F-FDG-PET-positive temporal lobe epilepsy using double inversion recovery and machine-learning

ObjectiveThe main objective of this study was to determine the ability of double inversion recovery (DIR) data coupled with machine-learning algorithms to distinguish normal individuals from epileptic subjects and to identify the laterality of the focus side in MRI-negative, PET-positive temporal lobe epilepsy (TLE) patients. Materials and methodsWe used whole-brain DIR data as the input features with which to train a linear support-vector machine model in 63 participants who underwent high-resolution structural MRI and DIR scans. The subjects included 20 left TLE patients, 19 right TLE patients, and 24 healthy controls (HCs). ResultsUsing the DIR data, we achieved a robust accuracy of 87.30% for discriminating among the left TLE, right TLE, and HC groups as well as 84.61%, 97.72%, and 93.02% prediction accuracies for distinguishing left TLE from right TLE, HC from right TLE, and HC from left TLE, respectively. InterpretationOur experimental results suggest that DIR data coupled with machine-learning algorithms provide a promising approach to identifying MRI-negative TLE patients, especially when fluorodeoxyglucose-PET is not available.

Exploring the Semantic Structure of WMS-IV Verbal Paired Associates using the Hub-and-Spoke Model.

This study aimed to identify a well-fitting and theoretically justified item-level latent factor structure for the Wechsler Memory Scales (WMS)-IV verbal paired associates (VerbalPA) subtest to facilitate the ease and accuracy of score interpretations for patients with lateralized temporal lobe epilepsy (TLE). Archival data were used from 250 heterogeneous neurosciences patients who were administered the WMS-IV as part of a standard neuropsychological assessment. Three theoretically motivated models for the latent structure of VerbalPA were tested using confirmatory factor analysis. The first model, based on cognitive principles of semantic processing from hub-and-spoke theory, tested whether performance is related to specific semantic features of target words. The second, motivated by the Cattell-Horn-Carroll (CHC) model of cognitive abilities, investigated whether the associative properties of items influence performance. A third, Hybrid model tested whether performance is related to both semantic and associative properties of items. The best-fitting model was tested for diagnostic group effects contrasting the heterogeneous neuroscience patients with subsets of left and right TLE (n = 51, n = 26, respectively) patients. The Hybrid model was found to have the best fit. Patients with left TLE scored significantly less well than the heterogeneous neurosciences sample on selected semantic factor scores, although the effect size was small. Future editions of the WMS may consider implementing a semantic scoring structure for the VerbalPA to facilitate test score interpretation. Additionally, these results suggest that principles of hub-and-spoke theory may be integrated into CHC cognitive ability taxonomy.

Computational support, not primacy, distinguishes compensatory memory reorganization in epilepsy.

Temporal lobe epilepsy is associated with impairment in episodic memory. A substantial subgroup, however, is able to maintain adequate memory despite temporal lobe pathology. Missing from prior work in cognitive reorganization is a direct comparison of temporal lobe epilepsy patients with intact status with those who are memory impaired. Little is known about the regional activations, functional connectivities and/or network reconfigurations that implement changes in primary computations or support functions that drive adaptive plasticity and compensated memory. We utilized task functional MRI on 54 unilateral temporal lobe epilepsy patients and 24 matched healthy controls during the performance of a paired-associate memory task to address three questions: (i) which regions implement paired-associate memory in temporal lobe epilepsy, and do they vary as a function of good versus poor performance, (ii) is there unique functional connectivity present during memory encoding that accounts for intact status by preservation of primary memory computations or the supportive computations that allow for intact memory responses and (iii) what features during memory encoding are most distinctive: is it the magnitude and location of regional activations, or the presence of enhanced functional connections to key structures such as the hippocampus? The study revealed non-dominant hemisphere regions (right posterior temporal regions) involving both increased regional activity and increased modulatory communication with the hippocampi as most important to intact memory in left temporal lobe epilepsy compared to impaired status. The profile involved areas that are neither contralateral homologues to left hemisphere memory areas, nor regions traditionally considered computationally primary for episodic memory. None of these areas of increased activation or functional connectivity were associated with advantaged memory in healthy controls. Our emphasis on different performance levels yielded insight into two forms of cognitive reorganization: computational primacy, where left temporal lobe epilepsy showed little change relative to healthy controls, and computational support where intact left temporal lobe epilepsy patients showed adaptive abnormalities. The analyses isolated the unique regional activations and mediating functional connectivity that implements truly compensatory reorganization in left temporal lobe epilepsy. The results provided a new perspective on memory deficits by making clear that they arise not just from the knockout of a functional hub, but from the failure to instantiate a complex set of reorganization responses. Such responses provided the computational support to ensure successful memory. We demonstrated that by keeping track of performance levels, we can increase understanding of adaptive brain responses and neuroplasticity in epilepsy.

Whole-brain functional correlates of memory formation in mesial temporal lobe epilepsy

The mesial temporal lobe is a key region for episodic memory. Accordingly, memory impairment is frequent in patients with mesial temporal lobe epilepsy. However, the functional relevance of potentially epilepsy-induced reorganisation for memory formation is still not entirely clear. Therefore, we investigated whole-brain functional correlates of verbal and non-verbal memory encoding and subsequent memory formation in 56 (25 right sided) mesial temporal lobe epilepsy patients and 21 controls. We applied an fMRI task of learning scenes, faces, and words followed by an out-of-scanner recognition test. During encoding of faces and scenes left and right mesial temporal lobe epilepsy patients had consistently reduced activation in the epileptogenic mesial temporal lobe compared with controls. Activation increases in patients were apparent in extra-temporal regions, partly associated with subsequent memory formation (left frontal regions and basal ganglia), and patients had less deactivation in regions often linked to the default mode and auditory networks. The more specific subsequent memory contrast indicated only marginal group differences. Correlating patients’ encoding activation with memory performance both within the paradigm and with independent clinical measures demonstrated predominantly increased contralateral mesio-temporal activation supporting intact memory performance. In left temporal lobe epilepsy patients, left frontal activation was also correlated with better verbal memory performance. Taken together, our findings hint towards minor extra-temporal plasticity in mesial temporal lobe epilepsy patients, which is in line with pre-surgical impairment and post-surgical memory decline in many patients. Further, data underscore the importance of particularly the contralateral mesial temporal lobe itself, to maintain intact memory performance.

Contributions of left and right anterior temporal lobes to semantic cognition: Evidence from patients with small temporopolar lesions

Decades of research have increased the understanding of the contribution of the anterior temporal lobes (ATLs) to semantic cognition. Nonetheless, whether semantic processing of different types of information show a selective relationship with left and right ATLs, or whether semantic processing in the ATLs is independent of the modality of the input is currently unknown. There exists evidence supporting each of these alternatives. A fundamental objection to these findings is that they were obtained from studies with patients with brain damage affecting extensive regions, sometimes bilaterally. In the current study, we assessed a group of 38 temporal lobe epilepsy (TLE) patients with either left or right small epileptogenic lesions with a battery of commonly used semantic tasks that tested verbal and non-verbal semantic processing. We found that left TLE patients exhibited worse performance than controls on the verbal semantic tasks, as expected, but also on the non-verbal semantic task. On the other hand, performance of the right TLE group did not differ from controls on the non-verbal task, but was worse on a semantic fluency task. When performance between patient groups was compared, we found that left TLE not only did worse than right TLE on the naming task, but also on the non-verbal associative memory task. When considered together, current data do not support a strong view of input modality differences between left and right ATLs. Additionally, they provide evidence indicating that the left and right ATLs do not make similar contributions to a singular functional system for semantic representation.

Quantitative analysis of double inversion recovery and FLAIR signals in temporal lobe epilepsy

This study aimed to quantitatively compare the signals from double inversion recovery (DIR) and fluid‐attenuated inversion recovery (FLAIR) in temporal lobe epilepsy (TLE) with a focus on anterior temporal lobe white matter abnormal signal (ATLAS) lesions. We recruited 59 patients with TLE (32 left, 27 right) and 24 healthy controls (HCs). All patients underwent 3T-MRI scans including 3D DIR and FLAIR images, and the images were normalized and compared among the three groups by the software program SPM 12. We also explored the association of the ATLAS with disease duration, seizure types, and the existence of hippocampal sclerosis (HS). As a result, compared to the HCs, there were significantly increased DIR signals in the ipsilateral anterior temporal white matter of both the left and right TLE patients. There was no significant signal difference in FLAIR images between the HCs and patients except for a trend-level increase in left TLE. There was also no significant association between the ATLAS and disease duration, seizure type, or HS. These results quantitatively confirmed the significant signal increases of DIR in the ipsilateral anterior temporal lobe in both left and right TLE, whereas FLAIR revealed no significant between-group differences. These findings may indicate greater usefulness of DIR compared to FLAIR for detecting ATLAS lesions.

<p>Impaired Cognitive Abilities in Siblings of Patients with Temporal Lobe Epilepsy</p>

PurposePatients with temporal lobe epilepsy (TLE) are at high risk of cognitive impairment. In addition to persistent seizures and antiepileptic drugs (AEDs), genetic factors also play an important role in the progression of cognitive deficits in TLE patients. Defining a cognitive endophenotype for TLE can provide information on the risk of cognitive impairment in patients. This study investigated the cognitive endophenotype of TLE by comparing neuropsychological function between patients with TLE, their unaffected siblings, and healthy control subjects.Patients and MethodsA total of 46 patients with TLE, 26 siblings, and 33 control subjects were recruited. Cognitive function (ie, general cognition, short- and long-term memory, attention, visuospatial and executive functions, and working memory) was assessed with a battery of neuropsychological tests. Differences between groups were evaluated by analysis of covariance, with age and years of education as covariates. The Kruskal–Wallis test was used to evaluate data that did not satisfy the homogeneity of variance assumption. Pairwise comparisons were adjusted by Bonferroni correction, with a significance threshold of P<0.05.ResultsPatients with TLE showed deficits in the information test (P<0.001), arithmetic test (P=0.003), digit symbol substitution test (P=0.001), block design test (BDT; P=0.005), and backward digit span test (P=0.001) and took a longer time to complete the Hayling test Part A (P=0.011) compared to controls. Left TLE patients tended to have worse executive function test scores than right TLE patients. The siblings of TLE patients showed deficits in the BDT (P=0.006, Bonferroni-corrected) relative to controls.ConclusionPatients with TLE exhibit cognitive impairment. Executive function is worse in patients with left TLE than in those with right TLE. Siblings show impaired visuospatial function relative to controls. Thus, cognitive deficits in TLE patients have a genetic component and are independent of seizures or AED use.

Interictal Heart Rate Variability Analysis Reveals Lateralization of Cardiac Autonomic Control in Temporal Lobe Epilepsy

Purpose: The temporal lobe, a critical hub for cognition, also plays a central role in the regulation of autonomic cardiovascular functions. Lesions in this area are usually associated with abnormalities in the regulation of heart rate (HR) and blood pressure (BP). The analysis of the heart rate variability (HRV) is useful to evaluate the cardiac parasympathetic nervous system activity. This study aims at comparing HRV changes occurring in two groups of patients suffering from Temporal Lobe Epilepsy (TLE). To that aim, we evaluated patients differentiated by the right or left location of the epileptic foci.Materials and Methods: Fifty-two adult patients with a diagnosis of TLE were enrolled. Each patient underwent a 20-min EEG + EKG recording in resting state. According to the localization of epileptic focus, patients were divided into two subgroups: right TLE (R-TLE) and left TLE (L-TLE). HRV parameters were calculated with a short-lasting analysis of EKG recordings. Time-domain and frequency domain-related, as well as non-linear analysis, parameters, were compared between the two groups.Results: Compared to the R-TLE group, L-TLE subjects showed a significant decrease in low frequency (LF) (p < 0.01) and low frequency/high-frequency ratio (LF/HF) (p < 0.001) as well as increased HF values (p < 0.01), a parameter indicative of the presence of an increased cardiac vagal tone. These results were also confirmed in the subgroup analysis that took into account the seizure types, responses to antiepileptic drugs, seizure frequencies, and etiology.Conclusions: The main finding of the study is that, compared to R-TLE, L-TLE is associated with increased cardiac vagal tone. These results indicate that patients with TLE exhibit a lateralized cardiac autonomic control. L-TLE patients may have a lower risk of developing cardiac dysfunctions and less susceptible to develop Sudden Death for Epilepsy (SUDEP).

Impaired naming performance in temporal lobe epilepsy: language fMRI responses are modulated by disease characteristics

ObjectiveTo investigate alterations of language networks and their relation to impaired naming performance in temporal lobe epilepsy (TLE) using functional MRI.MethodsSeventy-two adult TLE patients (41 left) and 36 controls were studied with overt auditory and picture naming fMRI tasks to assess temporal lobe language areas, and a covert verbal fluency task to probe frontal lobe language regions. Correlation of fMRI activation with clinical naming scores, and alteration of language network patterns in relation to epilepsy duration, age at onset and seizure frequency, were investigated with whole-brain multiple regression analyses.ResultsAuditory and picture naming fMRI activated the left posterior temporal lobe, and stronger activation correlated with better clinical naming scores. Verbal fluency MRI mainly activated frontal lobe regions. In left and right TLE, a later age of epilepsy onset related to stronger temporal lobe activations, while earlier age of onset was associated with impaired deactivation of extratemporal regions. In left TLE patients, longer disease duration and higher seizure frequency were associated with reduced deactivation. Frontal lobe language networks were unaffected by disease characteristics.ConclusionsWhile frontal lobe language regions appear spared, temporal lobe language areas are susceptible to dysfunction and reorganisation, particularly in left TLE. Early onset and long duration of epilepsy, and high seizure frequency, were associated with compromised activation and deactivation patterns of task-associated regions, which might account for impaired naming performance in individuals with TLE.

NR4A1 Methylation Associated Multimodal Neuroimaging Patterns Impaired in Temporal Lobe Epilepsy.

DNA hypermethylation has been widely observed in temporal lobe epilepsy (TLE), in which NR4A1 knockdown has been reported to be able to alleviate seizure severity in mouse model, while the underlying methylation-imaging pathway modulated by aberrant methylation levels of NR4A1 remains to be clarified in patients with TLE. Here, using multi-site canonical correlation analysis with reference, methylation levels of NR4A1 in blood were used as priori to guide fusion of three MRI features: functional connectivity (FC), fractional anisotropy (FA), and gray matter volume (GMV) for 56 TLE patients and 65 healthy controls. Post-hoc correlations were further evaluated between the identified NR4A1-associated brain components and disease onset. Results suggested that higher NR4A1 methylation levels in TLE were related with impaired temporal-cerebellar and occipital-cerebellar FC strength, lower FA in cingulum (hippocampus), and reduced GMV in putamen, temporal pole, and cerebellum. Moreover, findings were also replicated well in both patient subsets with either right TLE or left TLE only. Particularly, right TLE patients showed poorer cognitive abilities and more severe brain impairment than left TLE patients, especially more reduced GMV in thalamus. In summary, this work revealed a potential imaging-methylation pathway modulated by higher NR4A1 methylation in TLE via data mining, which may impact the above-mentioned multimodal brain circuits and was also associated with earlier disease onset and more cognitive deficits.