Left Mesial Temporal Lobe Epilepsy Research Articles

Functional connectivity abnormalities vary by amygdala subdivision and are associated with psychiatric symptoms in unilateral temporal epilepsy

The amygdala has been described as a structure affected by mesial temporal lobe epilepsy (MTLE). Indeed, it is suggested that amygdala abnormalities are related to the co-morbid depression and anxiety reported in MTLE. In this context, we investigated the relation between functional connectivity (FC) emerging from this structure in fMRI and depression and anxiety levels reported in MTLE patients. We focused on resting-state BOLD activity and evaluated whether FC differences emerge from each of three amygdala subdivisions (laterobasal, centromedial and superficial) in left and right MTLE groups, compared with healthy controls. Results revealed significant differences between patient groups and controls. Specifically, the left MTLE group showed abnormal FC for the left-sided seeds only. Furthermore, regardless of the seed, we observed more reliable differences between the right MTLE group and controls. Further analysis of these results revealed correlations between these impaired connectivities and psychiatric symptoms in both MTLE groups. Opposite relations, however, were highlighted: the more depressed or anxious the right MTLE patients, the closer their FC values approached controls; whereas the less anxious the left MTLE patients, the closer their FC values were normative. These results highlight how MTLE alter FC emerging from the limbic system. Overall, our data demonstrate that right TLE has a more maladaptive impact on emotion-related networks, in ways specific to the amygdala region, and the emotion symptom involved, than left TLE.

Ictal Modulation of Cardiac Repolarization, but Not of Heart Rate, Is Lateralized in Mesial Temporal Lobe Epilepsy

ObjectivesHuman and animal studies provided controversial data on asymmetric cortical representation of cardiac function, which may partially be due to different study designs and inter-individual variability. Here, we investigated whether seizure-related changes in heart rate (HR) and cardiac repolarization depend on the side of seizure-activity in people with mesial temporal lobe epilepsy (mTLE).MethodsTo account for inter-individual variability, EEG and ECG data were reviewed from patients with medically refractory mTLE undergoing pre-surgical video-EEG telemetry with at least 2 seizures arising from each hippocampus as assessed by bilateral hippocampal depths electrodes. RR and QT intervals were determined at different timepoints using a one-lead ECG. QT intervals were corrected for HR (QTc) using 4 established formulas.ResultsEighty-two seizures of 15 patients were analyzed. HR increased by ∼30% during hippocampal activity irrespective of the side (p = 0.411). QTc intervals were lengthened to a significantly greater extent during left hippocampal seizures (e.g. difference of QT intervals between preictal and ictal state using Bazett’s formula; left side 32.0±5.3 ms, right side 15.6±7.7 ms; p = 0.016). Abnormal QTc prolongation occurred in 7 of 41 left hippocampal seizures of 4 patients, and only in 2 of 37 right hippocampal seizures of 2 patients.ConclusionsSeizure-related modulation of cardiac repolarization, but not of HR, appears to depend on the side of ictal activity, strengthening the hypothesis of asymmetric cerebral representation of cardiac function. The clinical relevance of this is unclear, but may indicate an increased risk of abnormal ictal QT prolongation in people with left mTLE.

Disrupted Causal Connectivity in Mesial Temporal Lobe Epilepsy

Although mesial temporal lobe epilepsy (mTLE) is characterized by the pathological changes in mesial temporal lobe, function alteration was also found in extratemporal regions. Our aim is to investigate the information flow between the epileptogenic zone (EZ) and other brain regions. Resting-state functional magnetic resonance imaging (RS-fMRI) data were recorded from 23 patients with left mTLE and matched controls. We first identified the potential EZ using the amplitude of low-frequency fluctuation (ALFF) of RS-fMRI signal, then performed voxel-wise Granger causality analysis between EZ and the whole brain. Relative to controls, patients demonstrated decreased driving effect from EZ to thalamus and basal ganglia, and increased feedback. Additionally, we found an altered causal relation between EZ and cortical networks (default mode network, limbic system, visual network and executive control network). The influence from EZ to right precuneus and brainstem negatively correlated with disease duration, whereas that from the right hippocampus, fusiform cortex, and lentiform nucleus to EZ showed positive correlation. These findings demonstrate widespread brain regions showing abnormal functional interaction with EZ. In addition, increased ALFF in EZ was positively correlated with the increased driving effect on EZ in patients, but not in controls. This finding suggests that the initiation of epileptic activity depends not only on EZ itself, but also on the activity emerging in large-scale macroscopic brain networks. Overall, this study suggests that the causal topological organization is disrupted in mTLE, providing valuable information to understand the pathophysiology of this disorder.

Atypical neuropsychological profiles and cognitive outcome in mesial temporal lobe epilepsy

Patients with left mesial temporal lobe epilepsy (MTLE) have deficits in verbal memory processes, while patients with right MTLE have visuospatial memory impairment. However, atypical cognitive phenotypes among patients with MTLE may occur. In this study, we analyzed preoperative memory deficits in a cohort of 426 right-handed patients with unilateral MTLE. We also evaluated the cognitive outcome after anterior temporal lobectomy (ATL) of patients with atypical profiles in comparison with those with typical memory profile. We found that 25% of our patients had a typical cognitive profile, with verbal memory deficits associated with left side hippocampal sclerosis (HS) and visuospatial memory deficits associated with right side HS. However, 75% of our patients had atypical memory profiles. Despite these atypical profiles, patients submitted to right ATL had no significant cognitive deficit after surgery. In patients submitted to left ATL, the higher the presurgical scores on verbal memory and naming tests, the higher the cognitive decline after surgery.

Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy

The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change. Functional magnetic resonance imaging (fMRI) resting state scans and neuropsychological memory assessments (Warrington Recognition Tests for Words and Faces) were performed on 19 healthy controls, 20 patients with right mTLE, and 18 patients with left mTLE. In addition, postsurgical fMRI resting state and memory change (postsurgical memory performance-presurgical memory performance) data were available for half of these patients. Patients with mTLE showed reduced connectivity from the posterior cingulate cortex (PCC) to the epileptogenic HC and increased PCC connectivity to the contralateral HC. Stronger PCC connectivity to the epileptogenic HC was associated with better presurgical memory and with greater postsurgical memory decline. Stronger PCC connectivity to the contralateral HC was associated with less postsurgical memory decline. Following surgery, PCC connectivity to the remaining HC increased from presurgical values and showed enhanced correlation with postsurgical memory function. It is notable that this index was superior to others (hippocampal volume, preoperative memory scores) in explaining variance in memory change following surgery. Our results demonstrate the striking clinical significance of the brain's intrinsic connectivity in evaluating cognitive capacity and indicating the potential of postsurgical cognitive morbidity in patients with mTLE.

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.

Prediction of post-surgical seizure outcome in left mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy is the most common type of focal epilepsy and in its course often becomes refractory to anticonvulsant pharmacotherapy. A resection of the mesial temporal lobe structures is a promising option in these cases. However, approximately 30% of all patients remain with persistent seizures after surgery. In other words, reliable criteria for patients' outcome prediction are absent. To address this limitation, we investigated pre-surgical brain morphology of patients with unilateral left mesial temporal lobe epilepsy who underwent a selective amygdalohippocampectomy. Using support vector classification, we aimed to predict the post-surgical seizure outcome of each patient based on the pre-surgical T1-weighted structural brain images. Due to morphological gender differences and the evidence that men and women differ in onset, prevalence and symptomology in most neurological diseases, we investigated male and female patients separately. Thus, we benefitted from the capability to validate the reliability of our method in two independent samples. Notably, we were able to accurately predict the individual patients' outcome in the male (94% balanced accuracy) as well as in the female (96% balanced accuracy) group. In the male cohort relatively larger white matter volumes in the favorable as compared to the non-favorable outcome group were identified bilaterally in the cingulum bundle, fronto-occipital fasciculus and both caudate nuclei, whereas the left inferior longitudinal fasciculus showed relatively larger white matter volume in the non-favorable group. While relatively larger white matter volumes in the female cohort in the left inferior and right middle longitudinal fasciculus were associated with the favorable outcome, relatively larger white matter volumes in the non-favorable outcome group were identified bilaterally in the superior longitudinal fasciculi I and II. Here, we observed a clear lateralization and distinction of structures involved in the classification in men as compared to women with men exhibiting more alterations in the hemisphere contralateral to the seizure focus. In conclusion, individual post-surgical outcome predictions based on a single T1-weighted magnetic resonance image seem plausible and may thus support the routine pre-surgical workup of epilepsy patients.

Surgically proven coexistence of focal and generalized epilepsy: A case report

The coexistence of focal and idiopathic generalized epilepsy (IGE) is rarely observed, and the mechanism underlying this situation remains unknown. We report a 13-year-old girl with well-controlled generalized epilepsy and medically-refractory left temporal lobe epilepsy.She underwent intracranial EEG recording, which demonstrated two characteristic seizure patterns of generalized ictal onset and left mesial temporal onset. In addition, two types of interictal spike distribution, including the left mesial temporal region and generalized spikes, were also supportive of the coexistence of left mesial temporal lobe epilepsy and IGE. Thereafter, a left anterior temporal lobectomy and post-surgical medication significantly improved her seizure outcome. This case illustrates the importance of considering surgical management for patients with medically-intractable focal epilepsy coexisting with generalized epilepsy.

Computerized Cognitive Testing in Epilepsy (CCTE): A new method for cognitive screening

PurposeOptimized therapy in epilepsy should include individual care for cognitive functions. Here we introduce a computerized screening instrument, called “Computerized Cognitive Testing in Epilepsy” (CCTE), which allows for time-efficient repetitive assessment of the patient's cognitive profile regarding the domains of memory and attention, which are frequently impaired due to side effects of antiepileptic medication. MethodsThe CCTE battery takes 30min and covers tasks of verbal and figural memory, cognitive speed, attention and working memory. The patient's results are displayed immediately in comparison to age-related normative data. For evaluation of psychometrics and clinical correlations, data from patients of a tertiary referral epilepsy center (n=240) and healthy subjects (n=83) were explored. ResultsCCTE subtests show good reliability and concurrent validity compared to standard neuropsychological tests (p<0.01). Adverse cognitive effects of antiepileptic medication can be detected (p<0.05), e.g. significant negative effects of increasing drug load. Specific epilepsy subgroups, e.g. focal versus primary generalized epilepsy or right versus left mesial temporal lobe epilepsy, showed different CCTE profiles. ConclusionCCTE appears valuable for early detection of individual cognitive alterations related to medication. In addition, it displays interesting differences between epilepsy syndromes. The CCTE battery provides a standardized, time- and personnel-efficient assessment of cognitive functions open to a large number of patients and applicable for clinical and scientific use in epilepsy.

Granule cell dispersion is associated with memory impairment in right mesial temporal lobe epilepsy

PurposeWe analyzed the association of granule cell dispersion (GCD) with memory performance, clinical data and surgical outcome in a series of patients with mesial temporal lobe epilepsy (MTLE) and mesial temporal sclerosis (MTS). MethodHippocampal specimens from 54 patients with MTLE (27 patients with right MTLE and 27 with left MTLE) and unilateral MTS, who were separated into GCD and no-GCD groups and thirteen controls were studied. Quantitative neuropathological evaluation was performed using hippocampal sections stained with NeuN. Patients’ neuropsychological measures, clinical data, type of MTS and surgical outcome were reviewed. ResultsGCD occurred in 28 (51.9%) patients. No correlation between GCD and MTS pattern, clinical data or surgical outcome was found. The presence of GCD was correlated with worse visuospatial memory performance in right MTLE, but not with memory performance in left MTLE. ConclusionGCD may be related to memory impairment in right MTLE-MTS patients. However, the role of GCD in memory function is not precisely defined.

A voxel based morphometry (VBM) analysis of gray matter volume (GMV) loss in patients with refractory mesial temporal lobe epilepsy (MTLE) with and without depression

Objective: Study GMV differences in patients with depression, and mesial temporal lobe epilepsy (MTLE) with and without depression, compared to normal controls, by applying VBM technique. Method:We included 24 adults with MTLE without depression (17 women, 38.7 mean age), 24 adults with MTLE with depression (13 women, 39.6 mean age), and 96 healthy controls (75 women, 35.1 mean age). All MTLE patients were diagnosed by clinical, eletro and image features. Depression was diagnosed by a structured clinical interview (SCID I) and its sympomatology was checked by the Beck Depression Inventory. All patients underwent highresolution MRI scan. We performed VBM analysis on SPM5 and MATLAB7, comparing groups of patients with control group. The statistical analysis for all comparisons was performed with grand mean scaling, proportional threshold masking and implicit masking. The results were corrected for multiple comparisons using a false discovery rate of 5%. We also investigated the regional correlation between GMV in MTLE with depression, checking their performance on the BDI. This form of VBM was performed on the whole brain, using the general linear model protocols built into SPM5. Results: Half of the patients with MTLE also had depression. There wasno significative difference in termsof sex (p=0.371), epilepsyonset (p=0.495), epilepsy duration (p=0.129) and frequency of seizures (p=0.285) in thegroups ofMTLEwithorwithout depression.We found no significant difference between groups when the group of MTLE with depression was divided in right and left MTLE with depression (p=0.147). Besides the fact that the laterality was not a significant factor for depression in MTLE, the group of left MTLE with depression had a more severe depression than the group of right MTLE with depression (p=0.014). Therewasno regional correlation betweenGMV in MTLE with depression and their performance on the BDI. Patients with MTLE with depression had more areas of reduced volume. Conclusions: The neuropathologic changes of MTLE seem to be magnified in the presence of a chronic untreated depression disorder. The evidence of GMV loss in patients with MTLE with depression calls our attention to the importance of timely recognition and treatment of depression in patients with MTLE and also to the bidirectional relation between the two disorders and their frequent comorbid occurrence.

Patterns of altered functional connectivity in mesial temporal lobe epilepsy

In mesial temporal lobe epilepsy (MTLE) the epileptogenic area is confined to the mesial temporal lobe, but other cortical and subcortical areas are also affected and cognitive and psychiatric impairments are usually documented. Functional connectivity methods are based on the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which exhibit consistent and reproducible functional networks from resting state data. The aim of this study is to compare functional connectivity of patients with MTLE during the interictal period with healthy subjects. We hypothesize that patients show reduced functional connectivity compared to controls, the interest being to determine which regions show this reduction. We selected electroencephalography-functional magnetic resonance imaging (EEG-fMRI) resting state data without EEG spikes from 16 patients with right and 7 patients with left MTLE. EEG-fMRI resting state data of 23 healthy subjects matched for age, sex, and manual preference were selected as controls. Four volumes of interest in the left and right amygdalae and hippocampi (LA, RA, LH, and RH) were manually segmented in the anatomic MRI of each subject. The averaged BOLD time course within each volume of interest was used to detect brain regions with BOLD signal correlated with it. Group differences between patients and controls were estimated. In patients with right MTLE, group difference functional connectivity maps (RMTLE - controls) showed for RA and RH decreased connectivity with the brain areas of the default mode network (DMN), the ventromesial limbic prefrontal regions, and contralateral mesial temporal structures; and for LA and LH, decreased connectivity with DMN and contralateral hippocampus. Additional decreased connectivity was found between LA and pons and between LH and ventromesial limbic prefrontal structures. In patients with left MTLE, functional connectivity maps (LMTLE - controls) showed for LA and LH decreased connectivity with DMN, contralateral hippocampus, and bilateral ventromesial limbic prefrontal regions; no change in connectivity was detected for RA; and for RH, there was decreased connectivity with DMN, bilateral ventromesial limbic prefrontal regions, and contralateral amygdala and hippocampus. In unilateral MTLE, amygdala and hippocampus on the affected and to a lesser extent on the healthy side are less connected, and are also less connected with the dopaminergic mesolimbic and the DMNs. Changes in functional connectivity between mesial temporal lobe structures and these structures may explain cognitive and psychiatric impairments often found in patients with MTLE.

Extratemporal functional connectivity impairments at rest are related to memory performance in mesial temporal epilepsy

Mesial temporal lobe epilepsy (MTLE) is the most frequent form of focal epilepsy. At rest, there is evidence that brain abnormalities in MTLE are not limited to the epileptogenic region, but extend throughout the whole brain. It is also well established that MTLE patients suffer from episodic memory deficits. Thus, we investigated the relation between the functional connectivity seen at rest in fMRI and episodic memory impairments in MTLE. We focused on resting state BOLD activity and evaluated whether functional connectivity (FC) differences emerge from MTL seeds in left and right MTLE groups, compared with healthy controls. Results revealed significant FC reductions in both patient groups, localized in angular gyri, thalami, posterior cingulum and medial frontal cortex. We found that the FC between the left non-pathologic MTL and the medial frontal cortex was positively correlated with the delayed recall score of a non-verbal memory test in right MTLE patients, suggesting potential adaptive changes to preserve this memory function. In contrast, we observed a negative correlation between a verbal memory test and the FC between the left pathologic MTL and posterior cingulum in left MTLE patients, suggesting potential functional maladaptative changes in the pathologic hemisphere. Overall, the present study provides some indication that left MTLE may be more impairing than right MTLE patients to normative functional connectivity. Our data also indicates that the pattern of extra-temporal FC may vary as a function of episodic memory material and each hemisphere's capacity for cognitive reorganization.

Brain plasticity for verbal and visual memories in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: An fMRI study

We aimed to identify the brain areas involved in verbal and visual memory processing in normal controls and patients with unilateral mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS) by means of functional magnetic resonance imaging (fMRI). The sample comprised nine normal controls, eight patients with right MTLE, and nine patients with left MTLE. All subjects underwent fMRI with verbal and visual memory paradigms, consisting of encoding and immediate recall of 17 abstract words and 17 abstract drawings. A complex network including parietal, temporal, and frontal cortices seems to be involved in verbal memory encoding and retrieval in normal controls. Although similar areas of activation were identified in both patient groups, the extension of such activations was larger in the left-HS group. Patients with left HS also tended to exhibit more bilateral or right lateralized encoding related activations. This finding suggests a functional reorganization of verbal memory processing areas in these patients due to the failure of left MTL system. As regards visual memory encoding and retrieval, our findings support the hypothesis of a more diffuse and bilateral representation of this cognitive function in the brain. Compared to normal controls, encoding in the left-HS group recruited more widespread cortical areas, which were even more widespread in the right-HS group probably to compensate for their right mesial temporal dysfunction. In contrast, the right-HS group exhibited fewer activated areas during immediate recall than the other two groups, probably related to their greater difficulty in dealing with visual memory content.

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.

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

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. 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. 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). 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.

Mimetic automatisms expressing a negative affect in two patients with temporal lobe epilepsy

Ictal automatisms of fear or sadness, of which the patient is unaware and which are not preceded by a corresponding emotion, have not been well characterized. Of 557 patients admitted for video/EEG monitoring, 2 (0.36%) were identified who had automatisms of fear and sadness. One patient was found to have a sudden ictal expression of sadness of which he was not aware. The second patient showed a sudden fearful expression, followed by oral automatisms, staring, and amnesia for the event. Both patients had left mesial temporal lobe epilepsy. The patient with ictal fear underwent further invasive monitoring and became seizure free after a limited mesial temporal resection. The mesial temporal structures not only mediate emotional experiences, but can also activate stereotyped expressions of fear or sadness without the patient's awareness, arguing for an efferent pathway for expressing negative affects within the mesial temporal lobe.

Glucose-dependent insulinotropic peptide receptor expression in the hippocampus and neocortex of mesial temporal lobe epilepsy patients and rats undergoing pilocarpine induced status epilepticus

The glucose-dependent insulinotropic peptide receptor (GIPR) has been implicated with neuroplasticity and may be related to epilepsy. GIPR expression was analyzed by immunohistochemistry in the hippocampus (HIP) and neocortex (Cx) of rats undergoing pilocarpine induced status epilepticus (Pilo-SE), and in three young male patients with left mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) treated surgically. A combined GIPR immunohistochemistry and Fluoro-Jade staining was carried out to investigate the association between the GIPR expression and neuronal degeneration induced by Pilo-SE. GIPR was expressed in the cytoplasm of neurons from the HIP CA subfields, dentate gyrus (DG) and Cx of animals and human samples. The GIPR expression after the Pilo-SE induction increases significantly in the HIP after 1 h and 5 days, but not after 12 h or 50 days. In the Cx, the GIPR expression increases after 1 h, 12 h and 5 days, but not 50 days after the Pilo-SE. The expression of GIPR 12 h after Pilo-SE was inversely proportional to the Fluoro-Jade staining intensity. In the human tissue, GIPR expression patterns were similar to those observed in chronic Pilo-SE animals. No Fluoro-Jade stained cells were observed in the human sample. GIPR is expressed in human HIP and Cx. There was a time and region dependent increase of GIPR expression in the HIP and Cx after Pilo-SE that was inversely associated to neuronal degeneration.

Decision-making in temporal lobe epilepsy examined with the Iowa Gambling Task

Although memory, language, and executive functions have been extensively studied in patients with mesial temporal lobe epilepsy (MTLE), few investigations of the decision-making abilities of these patients have been performed. We studied implicit decision-making (decisions under ambiguity) in right and left MTLE patients using the Iowa Gambling Task. The Iowa Gambling Task is believed to detect deficits in decision-making caused by either ventromedial prefrontal cortex or amygdalo-hippocampal lesions. In the present study, MTLE patients scored poorly compared to healthy controls on this task, and right MTLE patients exhibited worse performance than left MTLE patients. Our findings indicate that the amygdalo-hippocampal complexes play important roles in decision-making. The right amygdalo-hippocampal complexes may play more important roles in implicit decision-making in particular.

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.