Dysfunction In Temporal Lobe Epilepsy Research Articles

White matter tract abnormalities are associated with executive dysfunction in temporal lobe epilepsy and hippocampal sclerosis (P12-1.010)

<h3>Objective:</h3> To evaluate the role of white-matter tract involvement in executive dysfunction in patients with temporal lobe epilepsy and unilateral hippocampal sclerosis (TLE-HS). <h3>Background:</h3> TLE-HS patients frequently display executive dysfunction (ED). The neuroanatomical substrate of ED in TLE-HS remains poorly understood. In this study, we investigated the role of white-matter tract involvement in ED in TLE-HS. <h3>Design/Methods:</h3> Patients with unilateral TLE-HS, aged 17–55, education&gt;=8 years, IQ&gt;=70, EEG findings of unilateral or bilateral temporal discharges were studied. Patients and healthy controls fulfilling the same inclusion criteria underwent the Stroop Color and Word Test (SCWT) and a 3T MRI with DTI sequences. DTI Fractional Anisotropy (FA) data was extracted and analyzed using FSL. FA maps were compared with Tract-Based Spatial Statistics (TBSS) voxel-wise analysis. Patients were classified as ED if performance in the SCWT was below minus 1.5 (−1.5) Standard Deviations of the mean performance of healthy controls. <h3>Results:</h3> 49 patients (30 left and 19 right HS) underwent the SCWT. Performance did not differ between right and left HS. Patients with normal and impaired executive function did not differ in disease duration, antiseizure medication load, and seizure frequency. Both patient groups showed diffuse FA decrease when compared to healthy controls. Compared to TLE-HS patients with normal SCWT performance, patients with ED had more pronounced FA alterations, showing statistically significant decreased FA in the superior longitudinal fasciculi, body of the corpus callosum, forceps major, corona radiata, inferior frontal-occipital fasciculus, uncinate fasciculus and corticospinal tract, and right thalamic radiations. <h3>Conclusions:</h3> In this TLE-HS patient population, executive dysfunction was associated with more pronounced widespread WM tract damage, in comparison with TLE-HS patients with preserved executive function. This finding underscores the role of microstructural WM damage in executive dysfunction in TLE-HS. <b>Disclosure:</b> Miss Solti has nothing to disclose. Mr. Mahler Ferreira Oliveira has nothing to disclose. Carla Adda has nothing to disclose. Rosa Valerio has nothing to disclose. Dr. Jorge has nothing to disclose. Katarina Lyra has nothing to disclose. Mr. Pastorello has nothing to disclose. Claudia Leite has nothing to disclose. Maria Otaduy has nothing to disclose. Dr. Castro has nothing to disclose.

Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE), one of the most common pharmaco-resistant epilepsies, is associated with pathology of paralimbic brain regions, particularly in the mesiotemporal lobe. Cognitive dysfunction in TLE is frequent, and particularly affects episodic memory. Crucially, these difficulties challenge the quality of life of patients, sometimes more than seizures, underscoring the need to assess neural processes of cognitive dysfunction in TLE to improve patient management. Our work harnessed a novel conceptual and analytical approach to assess spatial gradients of microstructural differentiation between cortical areas based on high-resolution MRI analysis. Gradients track region-to-region variations in intracortical lamination and myeloarchitecture, serving as a system-level measure of structural and functional reorganization. Comparing cortex-wide microstructural gradients between 21 patients and 35 healthy controls, we observed a reorganization of this gradient in TLE driven by reduced microstructural differentiation between paralimbic cortices and the remaining cortex with marked abnormalities in ipsilateral temporopolar and dorsolateral prefrontal regions. Findings were replicated in an independent cohort. Using an independent post-mortem dataset, we observed that in vivo findings reflected topographical variations in cortical cytoarchitecture. We indeed found that macroscale changes in microstructural differentiation in TLE reflected increased similarity of paralimbic and primary sensory/motor regions. Disease-related transcriptomics could furthermore show specificity of our findings to TLE over other common epilepsy syndromes. Finally, microstructural dedifferentiation was associated with cognitive network reorganization seen during an episodic memory functional MRI paradigm and correlated with interindividual differences in task accuracy. Collectively, our findings showing a pattern of reduced microarchitectural differentiation between paralimbic regions and the remaining cortex provide a structurally-grounded explanation for large-scale functional network reorganization and cognitive dysfunction characteristic of TLE.

The effect of hippocampal NR2B-containing NMDA receptors on chronic cognitive dysfunction in rats with temporal lobe epilepsy

BackgroundWe have previously reported that hippocampal long-term potentiation (LTP) was suppressed in temporal lobe epilepsy (TLE) rats. The N-methyl-D-aspartic acid receptors containing 2B subunit (NR2B-NMDARs) are indispensable to induce the LTP of hippocampus. However, it is still unknown whether the NR2B-NMDARs are implied with the cognitive dysfunction in TLE rats.MethodsThe TLE model was lithium chloride-pilocarpine (li-pilo) model. Morris water maze test was used to evaluate the cognitive function of epileptic rats. Expression of hippocampal NR2B-NMDAs was evaluated by western blotting. Stereotactic injection of NMDA, an agonist of NR2B-NMDARs, into the hippocampus of TLE rats was used to investigate the role of NR2B-NMDARs on cognitive dysfunction.ResultsCognitive function TLE rats was significantly reduced compared with controls in the Morris water maze test (P < 0.05). Western blotting data showed the down-expression of hippocampal NR2B-NMDARs and p-NR2B in TLE rats compared with the control (P < 0.05). In addition, hippocampal stereolocalization of NMDA injection improved partially the learning and memory in TLE rats (P < 0.05).ConclusionsDown-expression and low activity of hippocampal NR2B-NMDARs may be implied with chronic cognitive dysfunction in TLE rats.

Correlation Between the Functional Connectivity of Basal Forebrain Subregions and Vigilance Dysfunction in Temporal Lobe Epilepsy With and Without Focal to Bilateral Tonic-Clonic Seizure.

PurposePrevious research has shown that subcortical brain regions are related to vigilance in temporal lobe epilepsy (TLE). However, it is unknown whether alterations in the function and structure of basal forebrain (BF) subregions are associated with vigilance impairment in distinct kinds of TLE. We aimed to investigate changes in the structure and function BF subregions in TLE patients with and without focal to bilateral tonic-clonic seizures (FBTCS) and associated clinical features.MethodsA total of 50 TLE patients (25 without and 25 with FBTCS) and 25 healthy controls (HCs) were enrolled in this study. The structural and functional alterations of BF subregions in TLE were investigated using voxel-based morphometry (VBM) and resting-state functional connectivity (rsFC) analysis. Correlation analyses were utilized to investigate correlations between substantially altered imaging characteristics and clinical data from patients.ResultsFBTCS patients had a lower rsFC between Ch1-3 and the bilateral striatum as well as the left cerebellum posterior lobe than non-FBTCS patients. In comparison to non-FBTCS patients, the rsFC between Ch4 and the bilateral amygdala was also lower in FBTCS patients. Compared to HCs, the TLE patients had reduced rsFC between the BF subregions and the cerebellum, striatum, default mode network, frontal lobe, and occipital lobes. In the FBTCS group, the rsFC between the left Ch1-3 and striatum was positive correlated with the vigilance measures. In the non-FBTCS group, the rsFC between the left Ch4 and striatum was significantly negative correlated with the alertness measure.ConclusionThese results extend current understanding of the pathophysiology of impaired vigilance in TLE and imply that the BF subregions may serve as critical nodes for developing and categorizing TLE biomarkers.

Decoupling of functional and structural language networks in temporal lobe epilepsy.

ObjectiveTo identify functional and structural alterations in language networks of people with temporal lobe epilepsy (TLE), who frequently present with naming and word‐finding difficulties.MethodsFifty‐five patients with unilateral TLE (29 left) and 16 controls were studied with auditory and picture naming functional magnetic resonance imaging (fMRI) tasks. Activation maxima in the left posterobasal temporal lobe were used as seed regions for whole‐brain functional connectivity analyses (psychophysiological interaction). White matter language pathways were investigated using diffusion tensor imaging and neurite orientation dispersion and density imaging metrics extracted along fiber bundles starting from fMRI‐guided seeds. Regression analyses were performed to investigate the correlation of functional connectivity with diffusion MRI metrics.ResultsIn the whole group of patients and controls, weaker functional connectivity from the left posterobasal temporal lobe (1) to the bilateral anterior temporal lobe, precentral gyrus, and lingual gyrus during auditory naming and (2) to the bilateral occipital cortex and right fusiform gyrus during picture naming was associated with decreased neurite orientation dispersion and higher free water fraction of white matter tracts. Compared to controls, TLE patients exhibited fewer structural connections and an impaired coupling of functional and structural metrics.SignificanceTLE is associated with an impairment and decoupling of functional and structural language networks. White matter damage, as evidenced by diffusion abnormalities, may contribute to impaired functional connectivity and language dysfunction in TLE.

Magnetoencephalography Imaging Reveals Abnormal Information Flow in Temporal Lobe Epilepsy.

Background/Introduction:Widespread network disruption has been hypothesized to be an important predictor of outcomes in patients with refractory temporal lobe epilepsy (TLE). Most studies examining functional network disruption in epilepsy have largely focused on the symmetric bidirectional metrics of the strength of network connections. However, a more complete description of network dysfunction impacts in epilepsy requires an investigation of the potentially more sensitive directional metrics of information flow.Methods:This study describes a whole-brain magnetoencephalography-imaging approach to examine resting-state directional information flow networks, quantified by phase-transfer entropy (PTE), in patients with TLE compared with healthy controls (HCs). Associations between PTE and clinical characteristics of epilepsy syndrome are also investigated.Results:Deficits of information flow were specific to alpha-band frequencies. In alpha band, while HCs exhibit a clear posterior-to-anterior directionality of information flow, in patients with TLE, this pattern of regional information outflow and inflow was significantly altered in the frontal and occipital regions. The changes in information flow within the alpha band in selected brain regions were correlated with interictal spike frequency and duration of epilepsy.Conclusions:Impaired information flow is an important dimension of network dysfunction associated with the pathophysiological mechanisms of TLE.Impact statementA complete description of network dysfunction in temporal lobe epilepsy (TLE) requires investigation of the flow of information in brain networks. In this whole-brain magnetoencephalography imaging study, using an information theory measure, phase-transfer entropy, we examine the strength and directionality of information flow in patients with TLE. Abnormal information flow was documented and was associated with clinical measures related to epilepsy in certain brain regions. The approach described here may provide a useful framework to investigate network dysfunction in other neurological and psychiatric disorders.

Theta oscillation and functional connectivity alterations related to executive control in temporal lobe epilepsy with comorbid depression

ObjectiveDepression is widely acknowledged as the most common comorbidity of temporal lobe epilepsy (TLE), and executive control (EC) may be particularly impaired in patients with TLE with comorbid depression. The purpose of this study was to investigate brain network alterations in patients with TLE with or without depression using scalp electroencephalography (EEG), and to explore the potential mechanisms of TLE with comorbid depression. MethodsForty patients with TLE and 20 healthy controls (HC) were recruited for administered the BDI-II and HAMD-17 surveys. The patients with TLE were divided into those with depression (PDS, n = 20) and those without depression (nPDS, n = 20) according to the surveys. Neural oscillations and functional connectivity during performance of EC tasks were calculated during EEG. ResultsTheta oscillation and functional connectivity were significantly weakened in the PDS group compared to the nPDS and HC groups. Furthermore, the PDS group showed more serious EC dysfunction than nPDS group. ConclusionsOur results indicated that weakened theta oscillation and functional connectivity in the frontal lobe may be a mechanism of EC dysfunction in TLE with comorbid depression. SignificanceThe present results suggest that the alterations in frontal lobe connections may help predict the depression in patients with TLE.

Functional brain network mechanism of executive control dysfunction in temporal lobe epilepsy

BackgroundExecutive control dysfunction is observed in a sizable number of patients with temporal lobe epilepsy (TLE). Neural oscillations in the theta band are increasingly recognized as having a crucial role in executive control network. The purpose of this study was to investigate the alterations in the theta band in executive control network and explore the functional brain network mechanisms of executive control dysfunction in TLE patients.MethodsA total of 20 TLE patients and 20 matched healthy controls (HCs) were recruited in the present study. All participants were trained to perform the executive control task by attention network test while the scalp electroencephalogram (EEG) data were recorded. The resting state signals were collected from the EEG in the subjects with quiet and closed eyes conditions. Functional connectivity among EEGs in the executive control network and resting state network were respectively calculated.ResultsWe found the significant executive control impairment in the TLE group. Compared to the HCs, the TLE group showed significantly weaker functional connectivity among EEGs in the executive control network. Moreover, in the TLE group, we found that the functional connectivity was significantly positively correlated with accuracy and negatively correlated with EC_effect. In addition, the functional connectivity of the executive control network was significantly higher than that of the resting state network in the HCs. In the TLE group, however, there was no significant change in functional connectivity strengths between the executive control network and resting state network.ConclusionOur results indicate that the decreased functional connectivity in theta band may provide a potential mechanism for executive control deficits in TLE patients.

Temporal lobe epilepsy alters spatio-temporal dynamics of the hippocampal functional network.

Mesial temporal lobe epilepsy (TLE) is characterized by transient abnormal electrical activity originating in the hippocampus. The objective of this study was to characterize dynamic spatio-temporal fluctuations in hippocampal network connectivity in mTLE using functional connectivity (FC) mapping in 41 unilateral mTLE patients (28 right, 13 left) and 56 healthy control participants using 3T MRI. Dynamic FC was computed across the scan using sliding 60-s windows. This was compared to static FC computed using the whole 10-min functional MRI scan, and to the variance in the hippocampal functional MRI signal. Four states of healthy hippocampal dynamic FC were identified and compared to TLE patients. TLE patients fluctuated between these four states, but the hippocampus ipsilateral to the seizure focus spent more time in a state distinguished by lower prefrontal and parietal FC than the dominant healthy state. Increased time spent in this state was associated with increased impairment in static FC and increased variance in the hippocampal functional MRI signal. Overall, this work provides evidence that increases in variance in signal fluctuations occurring at the seizure focus in the hippocampus in patients with mTLE may contribute to disruptions in healthy FC network dynamics within an fMRI scan that contribute to decreases in static hippocampal FC. These alterations result in decreased hippocampal connectivity to bilateral prefrontal and parietal regions in TLE which may be related to behavior and cognitive impairments in these patients. Therefore, characterization of an individual patient's hippocampal dynamics at different time scales may provide more specific spatio-temporal profiles of network impairment that may be related to hippocampal dysfunction in TLE.

Thalamo-cortical network dysfunction in temporal lobe epilepsy

ObjectivesImaging and neurophysiological data shows that the cortical disfunction caused by focal epilepsy is not limited to the epileptic focus, thus raising the modern vision of focal epilepsy as a network disorder. The involvement of deep thalamo-cortical projections in temporal lobe epilepsy is a clear example. We aimed at demonstrating the interictal functional impairment of thalamo-cortical network in drug-naïve TLE patients through the study of high frequency oscillations of somatosensory evoked potentials (HF-SEP). MethodsTwelve healthy controls (HC; 8 females, 52.2 ± 17.3 years-old) and 12 drug-naïve TLE patients (8 females, 55.5 ± 21.5 years-old) underwent bilateral median HF-SEP, recorded by scalp electrodes. Cp3′-Fz and Cp4′-Fz traces were filtered (400–800 Hz) to evidence HF-SEP. ResultsHF-SEP duration in the affected hemisphere was significantly longer when compared to that of both the unaffected hemisphere and HC hemispheres. No significant inter-hemispheric differences were found in areas, powers and latencies of HF-SEP wavelets. ConclusionOur results demonstrate that TLE induces early interictal functional impairments of the thalamo-cortical network. SignificanceOur data strongly corroborates the vision of focal epilepsy as a network disorder and offers a new neurophysiological tool to test pharmacological, surgical and neuromodulatory therapies.

B-05 Age of Seizure Onset Predicted Categorical Fluency Switching and Anxiety in People with Temporal Lobe Epilepsy

Abstract Objective To examine whether demographic variables can assist in predicting executive dysfunction in individuals with temporal lobe epilepsy (TLE). Method Data were collected from presurgical evaluations of 13 individuals with TLE (67% females, mean age 34 ± 12) at the University of California, San Francisco Epilepsy Center. Executive functions were assessed using subtests from the D-KEFS (Verbal Fluency and Color/Word Interference Tests) and the Trail Making Test B. Given that depression and anxiety symptoms have been previously shown to be associated with poorer executive performance in individuals with TLE (Paradiso et al., 2001), predictability of the BDI-II and BAI scores were also tested. Linear regression analyses were used to test predictive values of demographic variables (age, age at seizure onset [ASO], years of education, gender, and right vs. left temporal epileptogenic source). Results ASO (β = .75, p = .021), gender (β = .632, p = .041), and education (β = .555, p = .05) explained 66% of the variance in the Verbal Fluency Switching scaled scores (R²=.66, F(4,8)= 3.876, p = .049). Education (β = .772, p = .009) and ASO (β = .686, p = .023) explained 70% of the variance in Verbal Fluency Switching Accuracy scaled scores (R² = .708, F(4,8) = 4.844, p = .028). Age (β = -.862, p = .003) and seizure onset (β = .457, p = .049) explained 52% of the variance in BAI scores (R² = .525, F(4,16) = 3.319, p = .032). Conclusions ASO predicted category switching and anxiety severity, while none of the demographic variables explored in this study predicted visuomotor switching. Further research should explore the efficacy of early interventions to protect against future executive dysfunction in TLE.

Correlation analysis about cranial magnetic resonance imaging and electroencephalogram abnormalities and event-related potentials in patients with temporal lobe epilepsy

Objective: To investigate and evaluate the correlation between event-related potentials, cranial magnetic resonance imaging and electroencephalogram on cognitive function in patients with temporal lobe epilepsy. Methods: According to the exclusion criteria, 60 adult temporal lobe epilepsy patients (24 males and 36 females, 34±13 years old of average age) were enrolled in the First Affiliated Hospital of Kunming Medical University from March 2017 to September 2018. The magnetic resonance imaging (MRI), 24 h video electroencephalogram (EEG) and event-related potentials (ERPs) were detected in all patients, comparing the latency of N1, P2, N2, P3 waves and the amplitude of P3 waves. Results: The mean latency of the waves of N1, P2, N2 and P3 and the mean amplitude of P3 wave were (108±25), (182±30), (256±33), (367±40) ms and (6.4±5.8) μV. There were significant differences in ERPs (latency of N1 wave, N2 wave and P3 wave) between the MRI abnormal group and the normal group (all P<0.05). There was a statistically significant difference in the ERPs (P3 wave latency) between EEG examination found epileptiform or paroxysmal slow waves release group and the patients with EEG normality in the past 1 year (P<0.05) and the EEG test results were positively correlated with the latency of P2, N2 and P3 waves in ERPs, and negatively correlated with the amplitude of P3 waves (P<0.05). Conclusion: Patients with cognitive dysfunction in temporal lobe epilepsy are more likely to have abnormal MRI and EEG in the head. Both of them show different effects on the cognitive process of patients in ERPs.

Decreased neurite density within frontostriatal networks is associated with executive dysfunction in temporal lobe epilepsy

ObjectiveExecutive dysfunction is observed in a sizable number of patients with refractory temporal lobe epilepsy (TLE). The frontostriatal network has been proposed to play a significant role in executive functioning, however, because of the complex architecture of these tracts, it is difficult to generate measures of fiber tract microstructure using standard diffusion tensor imaging. To examine the association between frontostriatal network compromise and executive dysfunction in TLE, we applied an advanced, multishell diffusion model, restriction spectrum imaging (RSI), that isolates measures of intraaxonal diffusion and may provide better estimates of fiber tract compromise in TLE. MethodsRestriction spectrum imaging scans were obtained from 32 patients with TLE [16 right TLE (RTLE); 16 left TLE (LTLE)] and 24 healthy controls (HC). An RSI-derived measure of intraaxonal anisotropic diffusion (neurite density; ND) was calculated for the inferior frontostriatal tract (IFS) and superior frontostriatal tract (SFS) and compared between patients with TLE and HC. Spearman correlations were performed to evaluate the relationships between ND of each tract and verbal (i.e., D-KEFS Category Switching Accuracy and Color–Word Interference Inhibition/Switching) and visuomotor (Trail Making Test) set-shifting performances in patients with TLE. ResultsPatients with TLE demonstrated reductions in ND of the left and right IFS, but not SFS, compared with HC. Reduction in ND of left and right IFS was associated with poorer performance on verbal set-shifting in TLE. Increases in extracellular diffusion (isotropic hindered; IH) were not associated with executive dysfunction in the patient group. SignificanceRestriction spectrum imaging-derived ND revealed microstructural changes within the IFS in patients with TLE, which was associated with poorer executive functioning. This suggests that axonal/myelin loss to fiber networks connecting the striatum to the inferior frontal cortex is likely contributing to executive dysfunction in TLE.

Evaluating executive function in patients with temporal lobe epilepsy using the frontal assessment battery

Previous studies have demonstrated executive dysfunction in patients with temporal lobe epilepsy (TLE). Frontal assessment battery (FAB) is a short neuropsychological tool that was developed for assessment of frontal lobe function in a clinical setting. The aim of the present study is to evaluate the clinical utility of FAB for detection of executive dysfunction in TLE patients.Forty-eight TLE patients and 48 sex and age-matched healthy controls participated in this study. Compared to healthy participants, the total FAB score was significantly lower among the TLE patients. TLE patients performed significantly worse at the mental flexibility, motor programming, sensitivity to interference and inhibitory control tasks. The duration of time has been passed since the last seizure was the only significant predictor of FAB score and patients who had a seizure less than a week before the evaluation time, had significantly lower FAB scores. The number of antiepileptic drugs (AEDs) did not influence the executive function in this study; however, sodium valproate was found to affect the mental flexibility.In conclusion, impaired executive function is common in TLE patients, and we suggest that FAB is a clinically applicable tool to monitor it. Moreover, we found that the time of the last seizure is a significant predictor of executive functioning and patients’ performance may become worse up to seven days after a seizure. We also recommend that clinicians evaluate the cognitive adverse effects of AEDs especially sodium valproate, which was found to affect the mental flexibility in this study.

Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance. Thirty-four patients (right TLE=17, left TLE=17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests. The number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume. In patients with TLE of long duration, IED occurrence was strongly related to cognitive deficits, most pronounced for frontal lobe function. These data suggest that IEDs reflect dysfunctional brain circuitry and may serve as an independent biomarker for cognitive comorbidity.

Semantic Processing Impairment in Patients with Temporal Lobe Epilepsy.

The impairment in episodic memory system is the best-known cognitive deficit in patients with temporal lobe epilepsy (TLE). Recent studies have shown evidence of semantic disorders, but they have been less studied than episodic memory. The semantic dysfunction in TLE has various cognitive manifestations, such as the presence of language disorders characterized by defects in naming, verbal fluency, or remote semantic information retrieval, which affects the ability of patients to interact with their surroundings. This paper is a review of recent research about the consequences of TLE on semantic processing, considering neuropsychological, electrophysiological, and neuroimaging findings, as well as the functional role of the hippocampus in semantic processing. The evidence from these studies shows disturbance of semantic memory in patients with TLE and supports the theory of declarative memory of the hippocampus. Functional neuroimaging studies show an inefficient compensatory functional reorganization of semantic networks and electrophysiological studies show a lack of N400 effect that could indicate that the deficit in semantic processing in patients with TLE could be due to a failure in the mechanisms of automatic access to lexicon.

An interictal EEG spectral metric for temporal lobe epilepsy lateralization

Visually-obvious abnormalities in the resting baseline EEG--slowing, spiking and high-frequency oscillations (HFOs)--are cardinal, though incompletely understood, features of the seizure onset zone in focal epilepsy. We hypothesized that evidence of cortical network dysfunction in temporal lobe epilepsy (TLE) would persist in the absence of visually-classifiable abnormalities in the baseline EEG recorded within the conventional passband, and that metrics of such dysfunction could serve as a lateralizing diagnostic in TLE. Epochs of resting EEG without significant abnormalities in light sleep over several days were compared between a group of 10 patients with proven TLE and 10 subjects without epilepsy. A novel laterality metric computed from the line length of normalized power spectra from the temporal channels was compared between the two groups. Significant group differences in spectral line length laterality metric were found between the TLE and control group. At the individual level, seven of 10 TLE patients had highly significant laterality metrics, all concordant with the known laterality of their disease. Detailed spectral analysis offers novel insight into TLE network behavior, independent of the orthodox abnormalities of EEG slowing, spikes or HFOs. The results may be deployed in a practical diagnostic manner, offer insight into the EEG manifestations of disordered cellular network architecture in TLE, and maybe understood through simple analogy with the theory of linear time-invariant physical systems.

Frontolimbic brain networks predict depressive symptoms in temporal lobe epilepsy

Psychiatric co-morbidities in epilepsy are of great concern. The current study investigated the relative contribution of structural and functional connectivity (FC) between medial temporal (MT) and prefrontal regions in predicting levels of depressive symptoms in patients with temporal lobe epilepsy (TLE). Twenty-one patients with TLE [11 left TLE (LTLE); 10 right TLE (RTLE)] and 20 controls participated. Diffusion tensor imaging was performed to obtain fractional anisotropy (FA) of the uncinate fasciculus (UF), and mean diffusivity (MD) of the amygdala (AM) and hippocampus (HC). Functional MRI was performed to obtain FC strengths between the AM and HC and prefrontal regions of interest including anterior prefrontal (APF), orbitofrontal, and inferior frontal regions. Participants self-reported depression symptoms on the Beck Depression Inventory-II. Greater depressive symptoms were associated with stronger FC of ipsilateral HC-APF, lower FA of the bilateral UF, and higher MD of the ipsilateral HC in LTLE, and with lower FA of the contralateral UF in RTLE. Regression analyses indicated that FC of the ipsilateral HC-APF was the strongest contributor to depression in LTLE, explaining 68.7% of the variance in depression scores. Both functional and microstructural measures of frontolimbic dysfunction were associated with depressive symptoms. These connectivity variables may be moderating which patients present with depression symptoms. In particular, FC MRI may provide a more sensitive measure of depression-related dysfunction, at least in patients with LTLE. Employing sensitive measures of frontolimbic network dysfunction in TLE may help provide new insight into mood disorders in epilepsy that could eventually guide treatment planning.

Attentional control in patients with temporal lobe epilepsy

Across different studies, patients with temporal lobe epilepsy (TLE) demonstrate impairments on numerous measures of attentional control that are classically associated with frontal lobe functioning. One aspect of attentional control that has not been examined in TLE is the ability to execute two modality-specific tasks concurrently. We sought to examine the status of dual-task coordination in TLE. We further examined the cohorts' performance on a range of traditional measures of attentional control. Eighteen TLE patients and 22 healthy controls participated in the study. Dual-task performance involved comparing the capacity to execute a tracking and a digit recall task simultaneously with the capacity to execute the tasks separately. We also administered measures of: set shifting (odd-man-out test), sustained attention (elevator counting), selective attention (elevator counting with distraction), and divided attention (trail making test). We found that the proportional decrement in dual-task performance relative to single-task performance did not vary between the groups (TLE=92.48%; controls=93.70%), nor was there a significant difference in sustained attention (p>.10). Patients with TLE did demonstrate marked deficits in selective attention (p<.0001), divided attention (p<.01), and set shifting (p<.01). These findings add to the knowledge about cognitive dysfunction in TLE, indicating that impairments in attentional control in TLE tend to be selective. The greatest deficits appear to be on tasks that invoke a high level of processing resources. In contrast, sustained attention is less compromised and the capacity to allocate cognitive resources appears to be normal in patients with TLE.

Astrocyte dysfunction in temporal lobe epilepsy: K+ channels and gap junction coupling

Astrocytes are endowed with the machinery to sense and respond to neuronal activity. Recent work has demonstrated that astrocytes play important physiological roles in the CNS, e.g., they synchronize action potential firing, ensure ion homeostasis, transmitter clearance and glucose metabolism, and regulate the vascular tone. Astrocytes are abundantly coupled through gap junctions, which is a prerequisite to redistribute elevated K(+) from sites of excessive neuronal activity to sites of lower extracellular K(+) concentration. Recent studies identified dysfunctional astrocytes as crucial players in epilepsy. Investigation of specimens from patients with pharmacoresistant temporal lobe epilepsy and epilepsy models revealed alterations in expression, localization, and function of astroglial inwardly rectifying K(+) (Kir) channels, particularly Kir4.1, which is suspected to entail impaired K(+) buffering. Gap junctions in astrocytes appear to play a dual role: on the one hand they counteract the generation of hyperactivity by facilitating clearance of elevated extracellular K(+) levels while in contrast, they constitute a pathway for energetic substrate delivery to fuel neuronal (hyper)activity. Recent work suggests that astrocyte dysfunction is causative of the generation or spread of seizure activity. Thus, astrocytes should be considered as promising targets for alternative antiepileptic therapies.