The effect of facial expression intensity on emotion recognition and psychosocial performance in patients with frontal or temporal lobe epilepsy.

PURPOSE: No studies have examined the relationship between the intensity of facial emotion expression and theory of mind (ToM) ability in people with epilepsy. This study aimed to explore facial emotion recognition in a group of patients with frontal (FLE) or temporal lobe epilepsy (TLE) and its relationship with the intensities of perceived facial emotion expressions, ToM, and social functioning. METHODS: Twenty-six patients with FLE or TLE and 30 matched controls were included in the study. All participants completed the facial emotion recognition test, Faux Pas Recognition (FPR) test measuring advanced ToM, Symptom Checklist-90-Revised, Social and Occupational Functioning Scale for Epilepsy (SOFSE), and background neuropsychological tests. RESULTS: The patient group was significantly worse than the control group in recognizing facial expressions of negative emotions, particularly for medium-intensity facial expression of fear. There was no significant difference between the groups in recognizing high-intensity fear facial expressions. The scores of FPR (overall and affective ToMs) in the patient group were significantly lower than those in the control group. Additionally, the facial emotion recognition was significantly associated with the total score of FPR, and the FPR total score remarkably correlated with the Communication subscale score of the SOFSE. CONCLUSIONS: Patients with FLE or TLE had impaired ability to recognize medium-intensity facial expressions of fear. Moreover, patients' ToM deficit significantly correlated not only with their emotion recognition problem but also with their social-communicative competence. Nevertheless, we also found that increasing the intensity of expression can improve the accuracy of emotion recognition in patients with epilepsy. These findings may provide considerations for further longitudinal studies and interventions on the social difficulties of people with epilepsy.

Functional Connectivity of the Corpus Callosum in Epilepsy Patients with Secondarily Generalized Seizures.

The corpus callosum (CC) plays an important role in generalization of seizure activity. We used resting-state function magnetic resonance imaging (rs-fMRI) to investigate the regional and interregional functional connectivity of CC in patients with magnetic resonance imaging (MRI)-negative and secondarily generalized seizures. We measured the multi-regional coherences of blood oxygen level-dependent (BOLD) signals via rs-fMRI, cortical thickness via high-resolution T1-weighted MRI, and white matter (WM) integrity via diffusion-tensor imaging in 16 epilepsy patients as well as in 16 age- and gender-matched healthy subjects. All patients had non-lesional MRI, medically well-controlled focal epilepsy and history of secondarily generalized convulsions. Individuals with epilepsy had significant differences in regional and interregional hypersynchronization of BOLD signals intrahemispherically and interhemispherically, but no difference in cortical thickness and WM integrity. The only area with increased regional hypersynchrony in WM was over the anterior CC, which also exhibited lower activation of neighboring resting-state networks. The present study revealed abnormal local and distant synchronization of spontaneous neural activities in epileptic patients with secondarily generalized seizures.

Increase in gray matter volume and white matter fractional anisotropy in the motor pathways of patients with secondarily generalized neocortical seizures.

PURPOSE: Convulsive motor activity is a clinical manifestation of secondarily generalized seizures evolving from different focal regions. The way in which the motor seizures present themselves is not very different from most of the generalized seizures in and between epilepsy patients. This might point towards the involvement of motor-related cortices and corticospinal pathway for wide spread propagation of epileptic activity. Our aim was to identify changes in the cerebral structures and to correlate clinical variables with structural changes particularly in the motor-related cortices and pathway of patients with generalized convulsions from different seizure foci. METHODS: Sixteen patients with focal onset and secondarily generalized seizures were included, along with sixteen healthy volunteers. Structural differences were analysed by measuring grey matter (GM) volume and thickness via T1-weighted MRI, and white matter (WM) fractional anisotropy (FA) via diffusion tensor imaging. GM and WM microstructural properties were compared between patients and controls by voxel- and surface- based analyses. Next, morphometric findings were correlated with seizure severity and disease duration to identify the pathologic process. KEY FINDINGS: In addition to widely reduced GM and WM properties, increased GM volume in the bilateral precentral gyri and paracentral lobules, and elevated regional FA in the bilateral corticospinal tracts adjacent to these motor -related GM were observed in patients and with higher statistical difference in the sub-patient group with drug-resistance. SIGNIFICANCE: The increment of GM volume and WM FA in the motor pathway positively correlated with severity and duration of epilepsy. The demonstrated microstructural changes of motor pathways imply a plastic process of motor networks in the patients with frequent generalization of focal seizures.

Resveratrol relieves Angiostrongylus cantonensis - Induced meningoencephalitis by activating sirtuin-1.

Resveratrol, a natural herbal compound found in high levels in grapes and red wine, is frequently used as activator of sirtuin-1. This study investigated the potential function of sirtuin-1 in regulating angiostrongyliasis meningoencephalitis in resveratrol-treated mice. Mice were subjected to meningoencephalitis to study the protective effect of resveratrol against meningoencephalitis and investigate the effects of sirtuin-1 activation on brain. Results demonstrated that sirtuin-1 level decreased in mice with meningoencephalitis and significantly increased in resveratrol-treated mice. Moreover, resveratrol treatment significantly reduced eosinophil counts, p65, Interferon-γ, interleukin (IL)-5, IL-33, and tumor necrosis factor-α levels, matrix metalloproteinase-9 activity, claudin-5 degradation, and blood-brain barrier permeability. By contrast, the anti-inflammatory factor IL-10 was significantly increased in resveratrol-treated mice. Resveratrol treatment was partially beneficial in controlling the pathological processes of angiostrongyliasis meningoencephalitis. The results demonstrate the neuroprotective and anti-inflammatory effects of resveratrol against Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis in mice. Treatment with sirtuin-1 agonist was given within a therapeutic window after A. cantonensis infection.

Altered structural and functional thalamocortical networks in secondarily generalized extratemporal lobe seizures.

Structural and functional abnormalities in the thalamocortical network in primary generalized epilepsies or mesial temporal lobe epilepsy have recently been identified by voxel-wise analyses of neuroimaging. However, evidence is needed regarding the profiles of the thalamocortical network in patients with secondarily generalized seizures from focal neocortical sources. We used high-resolution T1-weighted, diffusion-tensor and resting-state functional MR imaging (rs-fMRI) to examine 16 patients with secondarily generalized extratemporal lobe seizures and 16 healthy controls. All the patients were medically effective and MRI-negative. Using whole brain voxel-based morphometry (VBM) to compare the patients with the normal controls, we observed significantly decreased gray matter (GM) density in the thalamus and 3 frontal gyri and significantly reduced white matter (WM) fractional anisotropy (FA) in the bilateral anterior corona radiata of the patients. Alterations in the thalamocortical functional connectivity with different cortices were identified by the rs-fMRI analysis seeding of the whole thalamus. The prefrontal gyri with the greatest functional connectivity were also traced by seeding a sub-thalamic region that is demarcated in an atlas, in which the thalamic parcellation is based on the WM connectivity to the cortices. This sub-thalamic region anatomically contains the mediodorsal thalamic nucleus where, concordantly, there was a significant decrease in thalamic GM density in the VBM study. In contrast to the negative correlation between the disease duration and reduced thalamic densities and subcortical FA values, the strength of the functional thalamocortical connectivity had a paradoxical correlation. Our results conclusively indicate that generalized seizures with a focal cortical source are associated with structural and functional alterations in the thalamocortical network.

s-SMOOTH: Sparsity and Smoothness Enhanced EEG Brain Tomography.

EEG source imaging enables us to reconstruct current density in the brain from the electrical measurements with excellent temporal resolution (~ ms). The corresponding EEG inverse problem is an ill-posed one that has infinitely many solutions. This is due to the fact that the number of EEG sensors is usually much smaller than that of the potential dipole locations, as well as noise contamination in the recorded signals. To obtain a unique solution, regularizations can be incorporated to impose additional constraints on the solution. An appropriate choice of regularization is critically important for the reconstruction accuracy of a brain image. In this paper, we propose a novel Sparsity and SMOOthness enhanced brain TomograpHy (s-SMOOTH) method to improve the reconstruction accuracy by integrating two recently proposed regularization techniques: Total Generalized Variation (TGV) regularization and ℓ1-2 regularization. TGV is able to preserve the source edge and recover the spatial distribution of the source intensity with high accuracy. Compared to the relevant total variation (TV) regularization, TGV enhances the smoothness of the image and reduces staircasing artifacts. The traditional TGV defined on a 2D image has been widely used in the image processing field. In order to handle 3D EEG source images, we propose a voxel-based Total Generalized Variation (vTGV) regularization that extends the definition of second-order TGV from 2D planar images to 3D irregular surfaces such as cortex surface. In addition, the ℓ1-2 regularization is utilized to promote sparsity on the current density itself. We demonstrate that ℓ1-2 regularization is able to enhance sparsity and accelerate computations than ℓ1 regularization. The proposed model is solved by an efficient and robust algorithm based on the difference of convex functions algorithm (DCA) and the alternating direction method of multipliers (ADMM). Numerical experiments using synthetic data demonstrate the advantages of the proposed method over other state-of-the-art methods in terms of total reconstruction accuracy, localization accuracy and focalization degree. The application to the source localization of event-related potential data further demonstrates the performance of the proposed method in real-world scenarios.

A Spatially Focused Method for High Density Electrode-Based Functional Brain Mapping Applications.

Mapping the electric field of the brain with electrodes benefits from its superior temporal resolution but is prone to low spatial resolution property comparing with other modalities such as fMRI, which can directly impact the precision of clinical diagnosis. Simulations show that dense arrays with straightforwardly miniaturized electrodes in terms of size and pitch may not improve the spatial resolution but only strengthen the cross coupling between adjacent channels due to volume conduction. We present a new spatially focused method to improve the electrode spatial selectivity and consequently suppress the neural signal coupling from the sources in the vicinity. Compared with existing spatial filtering methods with fixed coefficients, the proposed method is adaptively optimized for the geometric parameters of the recording electrode arrays, including electrode size, pitch and source depth. The effective spatial bandwidth, characterized as Radius of Half Power, can be reduced by about 70% for ECoG and the case of distant sources scenarios. The proposed method has been applied to the analysis of high-frequency oscillations (HFOs) in seizures to study the ictal pathway in the epileptogenic region. The results reveal lucid HFO wavefront propagation in both preictal and ictal stages due to a 75% reduction in the coupling effect. The results also show that a specific power threshold of preictal HFOs is needed in order to initiate an epileptic seizure. This demonstrates that our method indeed facilitates the investigation of complex neurobiological signals preprocessing applications.

Automated segmentation and quantification of white matter hyperintensities in acute ischemic stroke patients with cerebral infarction.

White matter hyperintensities (WMHs) of presumed vascular origin are common in ageing population, especially in patients with acute cerebral infarction and the volume has been reported to be associated with mental impairment and the risk of hemorrhage from antithrombotic agents. WMHs delineation can be computerized to minimize human bias. However, the presence of cerebral infarcts greatly degrades the accuracy of WMHs detection and thus limits the application of computerized delineation to patients with acute cerebral infarction. We propose a computer-assisted segmentation method to depict WMHs in the presence of cerebral infarcts in combined T1-weighted, fluid attenuation inversion recovery, and diffusion-weighted magnetic resonance imaging (MRI). The proposed method detects WMHs by empirical threshold and atlas information, with subtraction of white matter voxels affected by acute infarction. The method was derived using MRI from 25 hemispheres with WMHs only and 13 hemispheres with both WMHs and cerebral infarcts. Similarity index (SI) and correlation were utilized to assess the agreement between the new automated method and a gold standard visually guided semi-automated method done by an expert rater. The proposed WMHs segmentation approach produced average SI, sensitivity and specificity of 83.142±11.742, 84.154±16.086 and 99.988±0.029% with WMHs only and of 68.826±14.036, 74.381±18.473 and 99.956±0.054% with both WMHs and cerebral infarcts in the derivation cohort. The performance of the proposed method with an external validation cohort was also highly consistent with that of the experienced rater.

Evaluation of subcortical grey matter abnormalities in patients with MRI-negative cortical epilepsy determined through structural and tensor magnetic resonance imaging.

BACKGROUND: Although many studies have found abnormalities in subcortical grey matter (GM) in patients with temporal lobe epilepsy or generalised epilepsies, few studies have examined subcortical GM in focal neocortical seizures. Using structural and tensor magnetic resonance imaging (MRI), we evaluated subcortical GM from patients with extratemporal lobe epilepsy without visible lesion on MRI. Our aims were to determine whether there are structural abnormalities in these patients and to correlate the extent of any observed structural changes with clinical characteristics of disease in these patients. METHODS: Twenty-four people with epilepsy and 29 age-matched normal subjects were imaged with high-resolution structural and diffusion tensor MR scans. The patients were characterised clinically by normal brain MRI scans and seizures that originated in the neocortex and evolved to secondarily generalised convulsions. We first used whole brain voxel-based morphometry (VBM) to detect density changes in subcortical GM. Volumetric data, values of mean diffusivity (MD) and fractional anisotropy (FA) for seven subcortical GM structures (hippocampus, caudate nucleus, putamen, globus pallidus, nucleus accumbens, thalamus and amygdala) were obtained using a model-based segmentation and registration tool. Differences in the volumes and diffusion parameters between patients and controls and correlations with the early onset and progression of epilepsy were estimated. RESULTS: Reduced volumes and altered diffusion parameters of subcortical GM were universally observed in patients in the subcortical regions studied. In the patient-control group comparison of VBM, the right putamen, bilateral nucleus accumbens and right caudate nucleus of epileptic patients exhibited a significantly decreased density Segregated volumetry and diffusion assessment of subcortical GM showed apparent atrophy of the left caudate nucleus, left amygdala and right putamen; reduced FA values for the bilateral nucleus accumbens; and elevated MD values for the left thalamus, right hippocampus and right globus pallidus A decreased volume of the nucleus accumbens consistently related to an early onset of disease. The duration of disease contributed to the shrinkage of the left thalamus. CONCLUSIONS: Patients with neocortical seizures and secondary generalisation had smaller volumes and microstructural anomalies in subcortical GM regions. Subcortical GM atrophy is relevant to the early onset and progression of epilepsy.

Through diffusion tensor magnetic resonance imaging to evaluate the original properties of neural pathways of patients with partial seizures and secondary generalization by individual anatomic reference atlas.

To investigate white matter (WM) abnormalities in neocortical epilepsy, we extract supratentorial WM parameters from raw tensor magnetic resonance images (MRI) with automated region-of-interest (ROI) registrations. Sixteen patients having neocortical seizures with secondarily generalised convulsions and 16 age-matched normal subjects were imaged with high-resolution and diffusion tensor MRIs. Automated demarcation of supratentorial fibers was accomplished with personalized fiber-labeled atlases. From the individual atlases, we observed significant elevation of mean diffusivity (MD) in fornix (cres)/stria terminalis (FX/ST) and sagittal stratum (SS) and a significant difference in fractional anisotropy (FA) among FX/ST, SS, posterior limb of the internal capsule (PLIC), and posterior thalamic radiation (PTR). For patients with early-onset epilepsy, the diffusivities of the SS and the retrolenticular part of the internal capsule were significantly elevated, and the anisotropies of the FX/ST and SS were significantly decreased. In the drug-resistant subgroup, the MDs of SS and PTR and the FAs of SS and PLIC were significantly different. Onset age was positively correlated with increases in FAs of the genu of the corpus callosum. Patients with neocortical seizures and secondary generalisation had microstructural anomalies in WM. The changes in WM are relevant to early onset, progression, and severity of epilepsy.

Automatic detection and quantification of acute cerebral infarct by fuzzy clustering and histographic characterization on diffusion weighted MR imaging and apparent diffusion coefficient map.

Determination of the volumes of acute cerebral infarct in the magnetic resonance imaging harbors prognostic values. However, semiautomatic method of segmentation is time-consuming and with high interrater variability. Using diffusion weighted imaging and apparent diffusion coefficient map from patients with acute infarction in 10 days, we aimed to develop a fully automatic algorithm to measure infarct volume. It includes an unsupervised classification with fuzzy C-means clustering determination of the histographic distribution, defining self-adjusted intensity thresholds. The proposed method attained high agreement with the semiautomatic method, with similarity index 89.9 ± 6.5%, in detecting cerebral infarct lesions from 22 acute stroke patients. We demonstrated the accuracy of the proposed computer-assisted prompt segmentation method, which appeared promising to replace the laborious, time-consuming, and operator-dependent semiautomatic segmentation.

Investigation of Subcortical Gray Matter in Patients with Non-lesional Neocortical Focal Epilepsy.

PURPOSE: To investigate whether there is any change in the subcortical gray matter of patients with neocortical focal epilepsy without visible magnetic resonance imaging (MRI) abnormalities. METHODS: MRI morphometric parameter data from 24 patients and 29 neurologically normal controls were analyzed. All of the MRI scans were reported to have no any anomaly. Differences were evaluated by vertex-wise shape analysis. RESULTS: A shape analysis showed significant surface reductions at the anterior-ventral and the posteriordorsal aspects of the bilateral thalami, the global left caudate nucleus, part of the bilateral dorsal putamen and the left hippocampus. CONCLUSION: Patients with focal seizures and secondary generalization had smaller volumes and microstructural anomalies in subcortical gray matter regions.

Comparison study of seizure detection using stationary and nonstationary methods.

We present an accurate seizure detection algorithm, and make a detailed comparison of two frequency analysis methods: a widely used stationary method - Fast Fourier Transform (FFT) and a relatively new nonstationary method - Hilbert-Huang Transform (HHT). Two public databases and one our own database were tested. The results show that our algorithm has very high accuracy compared with the state-of-the-art. More interestingly, it shows that the nonstationary method HHT offers better performance than the stationary method FFT in seizure detection. Therefore we propose that we should pay attention to the nonstationarity of EEG signal, since the "stationary assumption" may introduce some inaccuracy.

Features and futures: seizure detection in partial epilepsies.

Many factors underlying basic epileptic conditions determine the characteristics of epileptic seizures and the therapeutic outcome. Diagnosis and treatment rely on the clinical manifestations as well as electroencephalographic (EEG) epileptic activities. This article briefly reviews the fundamentals of the EEG, interictal, and ictal electrical activities of both extracranial and intracranial EEG of partial epilepsies, based on the information obtained from epilepsy patients who have undergone epilepsy surgery. The authors also present the status of their current research, focusing on decomposed seizure sources and the rendered spatial-temporal transitions in focal seizure.

Heart rate variability in patients with frontal lobe epilepsy.

OBJECTIVE: To identify autonomic dysregulation in frontal lobe epilepsy (FLE). METHODS: We studied 14 male and 11 female subjects with FLE and an equal number of matched healthy control subjects. Lead I electrocardiograms were obtained for 5 min in the interictal state during daytime. Frequency-domain analysis of heart rate variability was performed and the data subsequently converted to heart rate interval and high frequency (HF; 0.15-0.45 Hz) power which representing vagal or parasympathetic regulation, as well as low frequency (LF; 0.04-0.15 Hz) power and LF/(HF+LF) expressed in normalized units (LF%) (considered to mirror sympathetic regulation). Differences in data between groups were compared using t-test. RESULTS: The epilepsy group had a lower mean heart rate interval and a lower high frequency power. CONCLUSIONS: Patients with FLE have interictally faster heart rates, attributed to lower parasympathetic drive, which may contribute to the higher incidence of sudden death that is seen in this group of patients. This suggests that the mechanism of decreased HRV in patients with FLE is probably different from that in patients with temporal lobe epilepsy.

Heart rate variability in children with refractory generalized epilepsy.

OBJECTIVE: Repetitive seizures can alter the regulation of cardiac activity by the autonomic nervous system (ANS), and ANS dysregulation is thought to be associated with higher morbidity and mortality in epileptic patients, especially from sudden unexpected death. Few studies of interictal dysregulation of cardiac activity in children with epilepsy have been performed. In this study we characterize heart rate variability (HRV) in children with refractory generalized epilepsy. METHODS: Fifteen male and 15 female children, average age = 10.9+/-0.6 years, all with refractory generalized epilepsy were enrolled into the study group. A control group consisted of 15 males and 15 females with average age = 10.6+/-0.6 years. A lead I ECG was recorded for 5 min in the interictal period during daylight hours from each subject while awake. Frequency-domain analysis of HRV was performed using a non-parametric method of fast Fourier transformation. Changes of HRV were categorized into high frequency power (HF; 0.15-0.45 Hz), which represented vagal regulation, and low frequency power (LF; 0.04-0.15 Hz). LF/(HF+LF) expressed in normalized units (LF%) was considered to mirror sympathetic regulation. RESULTS: There were significant reductions in RR, LF, and HF in the study group when compared to controls. There was no significant difference in LF% between the two groups. CONCLUSIONS: We postulate that the lower HRV in our patients results from parasympathetic or vagal reduction. This suggests that decreased HRV in epileptic children occurs by a different mechanism than in adults with epilepsy.

Adult-onset autosomal dominant myoclonic epilepsy: report of a family with an overlooked epileptic syndrome.

OBJECTIVE: Myoclonic epilepsy is a common epileptic syndrome with high genetic contribution. We described a pedigree in which 10 individuals presented with a non-progressive, adult-onset myoclonic epilepsy. MATERIALS AND METHODS: The pedigree was constructed and analyzed. Six affected members were studied with clinical grounds, mental status, neurophysiology, video-electroencephalographic (EEG), brain magnetic resonance imaging (MRI) and mutational analysis of GABRA1 (GABRA1A, which endoces the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A). Clinical and EEG data were collected from six unaffected members. RESULTS: Autosomal dominant hereditary was shown. The age of seizure onset was approximately 40. All the individuals had myoclonic seizures and a normal cognitive level. Bilateral symmetric jerks of the shoulders, arms or legs featured the myoclonic seizure. Ictally, the consciousness was not affected. The ictal EEG demonstrated bilateral spikes-and-waves. The occurrence of myoclonic seizures was not associated with sleepiness. Rare generalized tonic-clonic seizures occurred in two individuals. No absence or accompanying involuntary movements were observed. A lower dose of valproic acid (200-500 mg/D) (clonazepam 0.5 mg/D in a patient) was required to stop the myoclonic seizures. CONCLUSIONS: The clinical features of late adult-onset autosomal dominant myoclonic epilepsy are similar to juvenile myoclonic epilepsy (JME), which is a common generalized epileptic syndrome with a significant hereditary component. But the age of onset, rare association of other seizure patterns, and non-relation of seizure onset to sleepiness suggest that this may be a distinct familial epileptic syndrome different from recognized familial myoclonic epilepsies.

Effect of multiple subpial transection on patients with uncontrolled atypical infantile spasms.

We report a favorable outcome of multiple sub-pial transaction (MST) in two patients who had intractable atypical infantile spasms preceded by partial seizures, without any lateralized magnetic resonance imaging (MRI) abnormalities.

Early-onset Parkinson's disease in a Chinese population: 99mTc-TRODAT-1 SPECT, Parkin gene analysis and clinical study.

Early Onset Parkinson's Disease (EOPD) is characterized by selective degeneration of nigrostriatal dopaminergic neurons and a marked response to levodopa. However, at present, few methods are available as diagnostic tools for EOPD except for 18F-DOPA PET. In addition, little is known about the correlation between clinical severity, neuroimaging grading and genetic susceptibility. In the present study, 99mTc-TRODAT-1 SPECT and brain MRI were used to identify 30 cases of non-familial EOPD from a Chinese cohort of 230. All 30 PD patients had an age of onset of less than 55 years (mean age at onset, 41.5+/-9.3 years). Each of the 30 EOPD cases was sub-classified into one of five stages based on the 99mTc-TRODAT-1 SPECT findings. In the early stages of PD (stages 1 and 2), a lower uptake of 99mTc-TRODAT-1 in the putamen was found, while uptake in the caudate nucleus was normal. In the latter stages (stages 3, 4, 5), 24 patients revealed a diffuse and uniform loss of 99mTc-TRODAT-1 uptake in the putamen and the caudate nucleus. Further, in conventional genetic studies of the 30 patients, six novel mutations were found in the Parkin gene, and these included five heterozygous point mutations (C441R, Q311H, V258M, C212G, and S193I) and one homozygous deletion (exon 10-12). Known polymorphisms (Ser167Asn, Val380Leu) were also found in a number of patients. However, gene dosage analysis did not reveal any compound heterozygous mutations in these 30 patients using quantitative duplex PCR. This is the first study to examine EOPD patients of Chinese ethnic background (not exhibiting a definite familial trait), to offer a complete genetic analysis of the Parkin gene, and to correlate clinical stages of the disease with dopamine re-uptake.