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Sample records for epileptic human hippocampus

  1. The functional organization of human epileptic hippocampus.

    PubMed

    Klimes, Petr; Duque, Juliano J; Brinkmann, Ben; Van Gompel, Jamie; Stead, Matt; St Louis, Erik K; Halamek, Josef; Jurak, Pavel; Worrell, Gregory

    2016-06-01

    The function and connectivity of human brain is disrupted in epilepsy. We previously reported that the region of epileptic brain generating focal seizures, i.e., the seizure onset zone (SOZ), is functionally isolated from surrounding brain regions in focal neocortical epilepsy. The modulatory effect of behavioral state on the spatial and spectral scales over which the reduced functional connectivity occurs, however, is unclear. Here we use simultaneous sleep staging from scalp EEG with intracranial EEG recordings from medial temporal lobe to investigate how behavioral state modulates the spatial and spectral scales of local field potential synchrony in focal epileptic hippocampus. The local field spectral power and linear correlation between adjacent electrodes provide measures of neuronal population synchrony at different spatial scales, ∼1 and 10 mm, respectively. Our results show increased connectivity inside the SOZ and low connectivity between electrodes in SOZ and outside the SOZ. During slow-wave sleep, we observed decreased connectivity for ripple and fast ripple frequency bands within the SOZ at the 10 mm spatial scale, while the local synchrony remained high at the 1 mm spatial scale. Further study of these phenomena may prove useful for SOZ localization and help understand seizure generation, and the functional deficits seen in epileptic eloquent cortex. PMID:27030735

  2. Differential Effect of Neuropeptides on Excitatory Synaptic Transmission in Human Epileptic Hippocampus.

    PubMed

    Ledri, Marco; Sørensen, Andreas T; Madsen, Marita G; Christiansen, Søren H; Ledri, Litsa Nikitidou; Cifra, Alessandra; Bengzon, Johan; Lindberg, Eva; Pinborg, Lars H; Jespersen, Bo; Gøtzsche, Casper R; Woldbye, David P D; Andersson, My; Kokaia, Merab

    2015-07-01

    Development of novel disease-modifying treatment strategies for neurological disorders, which at present have no cure, represents a major challenge for today's neurology. Translation of findings from animal models to humans represents an unresolved gap in most of the preclinical studies. Gene therapy is an evolving innovative approach that may prove useful for clinical applications. In animal models of temporal lobe epilepsy (TLE), gene therapy treatments based on viral vectors encoding NPY or galanin have been shown to effectively suppress seizures. However, how this translates to human TLE remains unknown. A unique possibility to validate these animal studies is provided by a surgical therapeutic approach, whereby resected epileptic tissue from temporal lobes of pharmacoresistant patients are available for neurophysiological studies in vitro. To test whether NPY and galanin have antiepileptic actions in human epileptic tissue as well, we applied these neuropeptides directly to human hippocampal slices in vitro. NPY strongly decreased stimulation-induced EPSPs in dentate gyrus and CA1 (up to 30 and 55%, respectively) via Y2 receptors, while galanin had no significant effect. Receptor autoradiographic binding revealed the presence of both NPY and galanin receptors, while functional receptor binding was only detected for NPY, suggesting that galanin receptor signaling may be impaired. These results underline the importance of validating findings from animal studies in human brain tissue, and advocate for NPY as a more appropriate candidate than galanin for future gene therapy trials in pharmacoresistant TLE patients. PMID:26134645

  3. Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus

    PubMed Central

    Johnson, Michael R.; Rossetti, Tiziana; Speed, Doug; Srivastava, Prashant K.; Chadeau-Hyam, Marc; Hajji, Nabil; Dabrowska, Aleksandra; Rotival, Maxime; Razzaghi, Banafsheh; Kovac, Stjepana; Wanisch, Klaus; Grillo, Federico W.; Slaviero, Anna; Langley, Sarah R.; Shkura, Kirill; Roncon, Paolo; De, Tisham; Mattheisen, Manuel; Niehusmann, Pitt; O’Brien, Terence J.; Petrovski, Slave; von Lehe, Marec; Hoffmann, Per; Eriksson, Johan; Coffey, Alison J.; Cichon, Sven; Walker, Matthew; Simonato, Michele; Danis, Bénédicte; Mazzuferi, Manuela; Foerch, Patrik; Schoch, Susanne; De Paola, Vincenzo; Kaminski, Rafal M.; Cunliffe, Vincent T.; Becker, Albert J.; Petretto, Enrico

    2015-01-01

    Gene-regulatory network analysis is a powerful approach to elucidate the molecular processes and pathways underlying complex disease. Here we employ systems genetics approaches to characterize the genetic regulation of pathophysiological pathways in human temporal lobe epilepsy (TLE). Using surgically acquired hippocampi from 129 TLE patients, we identify a gene-regulatory network genetically associated with epilepsy that contains a specialized, highly expressed transcriptional module encoding proconvulsive cytokines and Toll-like receptor signalling genes. RNA sequencing analysis in a mouse model of TLE using 100 epileptic and 100 control hippocampi shows the proconvulsive module is preserved across-species, specific to the epileptic hippocampus and upregulated in chronic epilepsy. In the TLE patients, we map the trans-acting genetic control of this proconvulsive module to Sestrin 3 (SESN3), and demonstrate that SESN3 positively regulates the module in macrophages, microglia and neurons. Morpholino-mediated Sesn3 knockdown in zebrafish confirms the regulation of the transcriptional module, and attenuates chemically induced behavioural seizures in vivo. PMID:25615886

  4. Increased extracellular levels of glutamate in the hippocampus of chronically epileptic rats.

    PubMed

    Soukupova, M; Binaschi, A; Falcicchia, C; Palma, E; Roncon, P; Zucchini, S; Simonato, M

    2015-08-20

    An increase in the release of excitatory amino acids has consistently been observed in the hippocampus during seizures, both in humans and animals. However, very little or nothing is known about the extracellular levels of glutamate and aspartate during epileptogenesis and in the interictal chronic period of established epilepsy. The aim of this study was to systematically evaluate the relationship between seizure activity and changes in hippocampal glutamate and aspartate extracellular levels under basal and high K(+)-evoked conditions, at various time-points in the natural history of experimental temporal lobe epilepsy, using in vivo microdialysis. Hippocampal extracellular glutamate and aspartate levels were evaluated: 24h after pilocarpine-induced status epilepticus (SE); during the latency period preceding spontaneous seizures; immediately after the first spontaneous seizure; in the chronic (epileptic) period. We found that (i) basal (spontaneous) glutamate outflow is increased in the interictal phases of the chronic period, whereas basal aspartate outflow remains stable for the entire course of the disease; (ii) high K(+) perfusion increased glutamate and aspartate outflow in both control and pilocarpine-treated animals, and the overflow of glutamate was clearly increased in the chronic group. Our data suggest that the glutamatergic signaling is preserved and even potentiated in the hippocampus of epileptic rats, and thus may favor the occurrence of spontaneous recurrent seizures. Together with an impairment of GABA signaling (Soukupova et al., 2014), these data suggest that a shift toward excitation occurs in the excitation/inhibition balance in the chronic epileptic state. PMID:26073699

  5. Spread of epileptic activity in human brain

    NASA Astrophysics Data System (ADS)

    Milton, John

    1997-03-01

    For many patients with medically refractory epilepsy surgical resection of the site of seizure onset (epileptic focus) offers the best hope for cure. Determination of the nature of seizure propagation should lead to improved methods for locating the epileptic focus (and hence reduce patient morbidity) and possibly to new treatment modalities directed at blocking seizure spread. Theoretical studies of neural networks emphasize the role of traveling waves for the propagation of activity. However, the nature of seizure propagation in human brain remains poorly characterized. The spread of epileptic activity in patients undergoing presurgical evaluation for epilepsy surgery was measured by placing subdural grids of electrodes (interelectrode spacings of 3-10 mm) over the frontal and temporal lobes. The exact location of each electrode relative to the surface of the brain was determined using 3--D MRI imaging techniques. Thus it is possible to monitor the spread of epileptic activity in both space and time. The observations are discussed in light of models for seizure propagation.

  6. Evolving networks in the human epileptic brain

    NASA Astrophysics Data System (ADS)

    Lehnertz, Klaus; Ansmann, Gerrit; Bialonski, Stephan; Dickten, Henning; Geier, Christian; Porz, Stephan

    2014-01-01

    Network theory provides novel concepts that promise an improved characterization of interacting dynamical systems. Within this framework, evolving networks can be considered as being composed of nodes, representing systems, and of time-varying edges, representing interactions between these systems. This approach is highly attractive to further our understanding of the physiological and pathophysiological dynamics in human brain networks. Indeed, there is growing evidence that the epileptic process can be regarded as a large-scale network phenomenon. We here review methodologies for inferring networks from empirical time series and for a characterization of these evolving networks. We summarize recent findings derived from studies that investigate human epileptic brain networks evolving on timescales ranging from few seconds to weeks. We point to possible pitfalls and open issues, and discuss future perspectives.

  7. Hippocampus and epilepsy: findings from human tissues

    PubMed Central

    Huberfeld, Gilles; Blauwblomme, Thomas; Miles, Richard

    2015-01-01

    Surgical removal of the epileptogenic zone provides an effective therapy for several epileptic syndromes. This surgery offers the opportunity to study pathological activity in living human tissue for pharmacoresistant partial epilepsy syndromes including (1) temporal lobe epilepsies with hippocampal sclerosis, (2) cortical dysplasias, (3) epilepsies associated with tumors and (4) developmental malformations. Slices of tissue from patient with these syndromes retain functional neuronal networks and may generate epileptic activities. The properties of cells in this tissue may not be greatly changed, but excitatory synaptic transmission is often enhanced and GABAergic inhibition is preserved. Typically epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated, not in the hippocampus but in the subiculum an output region which projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells which paradoxically excite about 20% of subicular pyramidal cells while simultaneously inhibiting the majority. Interictal discharges thus depend on both GABAergic and glutamatergic signaling. The depolarizing effects of GABA depend on a pathological elevation in levels of chloride in some subicular cells, similar to those of developmentally immature cells. Such defect is caused by a perturbed expression of the cotransporters regulating intracellular chloride concentration, the importer NKCC1 and the extruder KCC2. Blockade of NKCC1 actions by the diuretic bumetanide, restores intracellular chloride and thus hyperpolarizing GABAergic actions so suppressing interictal activity. PMID

  8. Hippocampus and epilepsy: Findings from human tissues.

    PubMed

    Huberfeld, G; Blauwblomme, T; Miles, R

    2015-03-01

    Surgical removal of the epileptogenic zone provides an effective therapy for several focal epileptic syndromes. This surgery offers the opportunity to study pathological activity in living human tissue for pharmacoresistant partial epilepsy syndromes including temporal lobe epilepsies with hippocampal sclerosis, cortical dysplasias, epilepsies associated with tumors and developmental malformations. Slices of tissue from patients with these syndromes retain functional neuronal networks and may generate epileptic activities. The properties of cells in this tissue may not be greatly changed, but excitatory synaptic transmission is often enhanced and GABAergic inhibition is preserved. Typically epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in the neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated, not in the hippocampus but in the subiculum, an output region, which projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells, which paradoxically excite about 20% of subicular pyramidal cells while simultaneously inhibiting the majority. Interictal discharges thus depend on both GABAergic and glutamatergic signaling. The depolarizing effects of GABA depend on a pathological elevation in levels of chloride in some subicular cells, similar to those of developmentally immature cells. Such defect is caused by a perturbed expression of the cotransporters regulating intracellular chloride concentration, the importer NKCC1 and the extruder KCC2. Blockade of NKCC1 actions by the diuretic bumetanide restores intracellular chloride and thus hyperpolarizing GABAergic actions and consequently suppressing interictal

  9. Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic activity in mouse hippocampus.

    PubMed

    Chali, Farah; Djelti, Fathia; Eugene, Emmanuel; Valderrama, Mario; Marquer, Catherine; Aubourg, Patrick; Duykaerts, Charles; Miles, Richard; Cartier, Nathalie; Navarro, Vincent

    2015-05-01

    Elevations in neuronal cholesterol have been associated with several degenerative diseases. An enhanced excitability and synchronous firing in surviving neurons are among the sequels of neuronal death in these diseases and also in some epileptic syndromes. Here, we attempted to increase neuronal cholesterol levels, using a short hairpin RNA to suppress expression of the enzyme cytochrome P450 family 46, subfamily A, polypeptide 1 gene (CYP46A1). This protein hydroxylates cholesterol and so facilitates transmembrane extrusion. A short hairpin RNA CYP46A1construction coupled to the adeno-associated virus type 5 was injected focally and unilaterally into mouse hippocampus. It was selectively expressed first in neurons of the cornu ammonis (hippocampus) (CA)3a region. Cytoplasmic and membrane cholesterol increased, and the neuronal soma volume increased and then decreased before pyramidal cells died. As CA3a pyramidal cells died, interictal electroencephalographic (EEG) events occurred during exploration and non-rapid eye movement sleep. With time, neuronal death spread to involve pyramidal cells and interneurons of the CA1 region. CA1 neuronal death was correlated with a delayed local expression of phosphorylated tau. Astrocytes were activated throughout the hippocampus and microglial activation was specific to regions of neuronal death. CA1 neuronal death was correlated with distinct aberrant EEG activity. During exploratory behaviour and rapid eye movement sleep, EEG oscillations at 7-10 Hz (theta) could accelerate to 14-21 Hz (beta) waves. They were accompanied by low-amplitude, high-frequency oscillations of peak power at ~300 Hz and a range of 250-350 Hz. Although episodes of EEG acceleration were not correlated with changes in exploratory behaviour, they were followed in some animals by structured seizure-like discharges. These data strengthen links between increased cholesterol, neuronal sclerosis and epileptic behaviour. PMID:25847620

  10. Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic activity in mouse hippocampus

    PubMed Central

    Chali, Farah; Djelti, Fathia; Eugene, Emmanuel; Valderrama, Mario; Marquer, Catherine; Aubourg, Patrick; Duykaerts, Charles; Miles, Richard; Cartier, Nathalie; Navarro, Vincent

    2015-01-01

    Elevations in neuronal cholesterol have been associated with several degenerative diseases. An enhanced excitability and synchronous firing in surviving neurons are among the sequels of neuronal death in these diseases and also in some epileptic syndromes. Here, we attempted to increase neuronal cholesterol levels, using a short hairpin RNA (shRNA) to suppress expression of the enzyme CYP46A1. This protein hydroxylates cholesterol and so facilitates trans-membrane extrusion. A sh-RNA CYP46A1construction coupled to an adeno-associated virus (AAV5) was injected focally and unilaterally into mouse hippocampus. It was selectively expressed first in neurons of the CA3a region. Cytoplasmic and membrane cholesterol increased, neuronal soma volume increased and then decreased before pyramidal cells died. As CA3a pyramidal cells died, inter-ictal EEG events occurred during exploration and non-REM sleep. With time, neuronal death spread to involve pyramidal cells and interneurons of the CA1 region. CA1 neuronal death was correlated with a delayed local expression of phosphorylated tau. Astrocytes were activated throughout the hippocampus and microglial activation was specific to regions of neuronal death. CA1 neuronal death was correlated with distinct aberrant EEG activity. During exploratory behaviour and rapid eye movement sleep, EEG oscillations at 7-10 Hz (theta) could accelerate to 14-21 Hz (beta) waves. They were accompanied by low amplitude, high-frequency oscillations of peak power at ~300Hz and a range of 250-350 Hz. While episodes of EEG acceleration were not correlated with changes in exploratory behaviour, they were followed in some animals by structured seizure-like discharges. These data strengthen links between increased cholesterol, neuronal sclerosis and epileptic behavior PMID:25847620

  11. Concepts of Connectivity and Human Epileptic Activity

    PubMed Central

    Lemieux, Louis; Daunizeau, Jean; Walker, Matthew C.

    2011-01-01

    This review attempts to place the concept of connectivity from increasingly sophisticated neuroimaging data analysis methodologies within the field of epilepsy research. We introduce the more principled connectivity terminology developed recently in neuroimaging and review some of the key concepts related to the characterization of propagation of epileptic activity using what may be called traditional correlation-based studies based on EEG. We then show how essentially similar methodologies, and more recently models addressing causality, have been used to characterize whole-brain and regional networks using functional MRI data. Following a discussion of our current understanding of the neuronal system aspects of the onset and propagation of epileptic discharges and seizures, we discuss the most advanced and ambitious framework to attempt to fully characterize epileptic networks based on neuroimaging data. PMID:21472027

  12. Cortical GABAergic excitation contributes to epileptic activities around human glioma

    PubMed Central

    Pallud, Johan; Varlet, Pascale; Cresto, Noemie; Baulac, Michel; Duyckaerts, Charles; Kourdougli, Nazim; Chazal, Geneviève; Devaux, Bertrand; Rivera, Claudio; Miles, Richard; Capelle, Laurent; Huberfeld, Gilles

    2015-01-01

    Rationale Diffuse brain gliomas induce seizures in a majority of patients. As in most epileptic disorders, excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glial tumor cells. Thus the contribution of GABAergic mechanisms which depend on intracellular chloride and which are defective or pro-epileptic in other structural epilepsies merits closer study. Objective We studied in neocortical slices from the peritumoral security margin resected around human brain gliomas, the occurrence, networks, cells and signaling basis of epileptic activities. Results Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges. These events were synchronized, with a high frequency oscillation signature, in superficial layers of neocortex around glioma areas with tumor infiltration. Interictal-like events depended on both glutamatergic transmission and on depolarizing GABAergic signaling. About 65% of pyramidal cells were depolarized by GABA released by interneurons. This effect was related to perturbations in Chloride homeostasis, due to changes in expression of chloride co-transporters: KCC2 was reduced and expression of NKCC1 increased. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. Conclusions Epileptic activities are sustained by excitatory effects of GABA in the peritumoral human neocortex, as in temporal lobe epilepsies. Glutamate and GABA signaling are involved in oncogenesis and chloride homeostasis is perturbed. These same factors, induce an imbalance between synaptic excitatory and inhibition underly epileptic discharges in tumor patients. PMID:25009229

  13. Mnemonic convergence in the human hippocampus

    PubMed Central

    Backus, Alexander R.; Bosch, Sander E.; Ekman, Matthias; Grabovetsky, Alejandro Vicente; Doeller, Christian F.

    2016-01-01

    The ability to form associations between a multitude of events is the hallmark of episodic memory. Computational models have espoused the importance of the hippocampus as convergence zone, binding different aspects of an episode into a coherent representation, by integrating information from multiple brain regions. However, evidence for this long-held hypothesis is limited, since previous work has largely focused on representational and network properties of the hippocampus in isolation. Here we identify the hippocampus as mnemonic convergence zone, using a combination of multivariate pattern and graph-theoretical network analyses of functional magnetic resonance imaging data from humans performing an associative memory task. We observe overlap of conjunctive coding and hub-like network attributes in the hippocampus. These results provide evidence for mnemonic convergence in the hippocampus, underlying the integration of distributed information into episodic memory representations. PMID:27325442

  14. Mnemonic convergence in the human hippocampus.

    PubMed

    Backus, Alexander R; Bosch, Sander E; Ekman, Matthias; Grabovetsky, Alejandro Vicente; Doeller, Christian F

    2016-01-01

    The ability to form associations between a multitude of events is the hallmark of episodic memory. Computational models have espoused the importance of the hippocampus as convergence zone, binding different aspects of an episode into a coherent representation, by integrating information from multiple brain regions. However, evidence for this long-held hypothesis is limited, since previous work has largely focused on representational and network properties of the hippocampus in isolation. Here we identify the hippocampus as mnemonic convergence zone, using a combination of multivariate pattern and graph-theoretical network analyses of functional magnetic resonance imaging data from humans performing an associative memory task. We observe overlap of conjunctive coding and hub-like network attributes in the hippocampus. These results provide evidence for mnemonic convergence in the hippocampus, underlying the integration of distributed information into episodic memory representations. PMID:27325442

  15. Evolving functional network properties and synchronizability during human epileptic seizures

    NASA Astrophysics Data System (ADS)

    Schindler, Kaspar A.; Bialonski, Stephan; Horstmann, Marie-Therese; Elger, Christian E.; Lehnertz, Klaus

    2008-09-01

    We assess electrical brain dynamics before, during, and after 100 human epileptic seizures with different anatomical onset locations by statistical and spectral properties of functionally defined networks. We observe a concave-like temporal evolution of characteristic path length and cluster coefficient indicative of a movement from a more random toward a more regular and then back toward a more random functional topology. Surprisingly, synchronizability was significantly decreased during the seizure state but increased already prior to seizure end. Our findings underline the high relevance of studying complex systems from the viewpoint of complex networks, which may help to gain deeper insights into the complicated dynamics underlying epileptic seizures.

  16. Gene expression profiling in developing human hippocampus.

    PubMed

    Zhang, Yan; Mei, Pinchao; Lou, Rong; Zhang, Michael Q; Wu, Guanyun; Qiang, Boqin; Zhang, Zhengguo; Shen, Yan

    2002-10-15

    The gene expression profile of developing human hippocampus is of particular interest and importance to neurobiologists devoted to development of the human brain and related diseases. To gain further molecular insight into the developmental and functional characteristics, we analyzed the expression profile of active genes in developing human hippocampus. Expressed sequence tags (ESTs) were selected by sequencing randomly selected clones from an original 3'-directed cDNA library of 150-day human fetal hippocampus, and a digital expression profile of 946 known genes that could be divided into 16 categories was generated. We also used for comparison 14 other expression profiles of related human neural cells/tissues, including human adult hippocampus. To yield more confidence regarding differential expression, a method was applied to attach normalized expression data to genes with a low false-positive rate (<0.05). Finally, hierarchical cluster analysis was used to exhibit related gene expression patterns. Our results are in accordance with anatomical and physiological observations made during the developmental process of the human hippocampus. Furthermore, some novel findings appeared to be unique to our results. The abundant expression of genes for cell surface components and disease-related genes drew our attention. Twenty-four genes are significantly different from adult, and 13 genes might be developing hippocampus-specific candidate genes, including wnt2b and some Alzheimer's disease-related genes. Our results could provide useful information on the ontogeny, development, and function of cells in the human hippocampus at the molecular level and underscore the utility of large-scale, parallel gene expression analyses in the study of complex biological phenomena. PMID:12271469

  17. Traveling Theta Waves in the Human Hippocampus.

    PubMed

    Zhang, Honghui; Jacobs, Joshua

    2015-09-01

    The hippocampal theta oscillation is strongly correlated with behaviors such as memory and spatial navigation, but we do not understand its specific functional role. One hint of theta's function came from the discovery in rodents that theta oscillations are traveling waves that allow parts of the hippocampus to simultaneously exhibit separate oscillatory phases. Because hippocampal theta oscillations in humans have different properties compared with rodents, we examined these signals directly using multielectrode recordings from neurosurgical patients. Our findings confirm that human hippocampal theta oscillations are traveling waves, but also show that these oscillations appear at a broader range of frequencies compared with rodents. Human traveling waves showed a distinctive pattern of spatial propagation such that there is a consistent phase spread across the hippocampus regardless of the oscillations' frequency. This suggests that traveling theta oscillations are important functionally in humans because they coordinate phase coding throughout the hippocampus in a consistent manner. Significance statement: We show for the first time in humans that hippocampal theta oscillations are traveling waves, moving along the length of the hippocampus in a posterior-anterior direction. The existence of these traveling theta waves is important for understanding hippocampal neural coding because they cause neurons at separate positions in the hippocampus to experience different theta phases simultaneously. The theta phase that a neuron measures is a key factor in how that cell represents behavioral information. Therefore, the existence of traveling theta waves indicates that, to fully understand how a hippocampal neuron represents information, it is vital to also account for that cell's location in addition to conventional measures of neural activity. PMID:26354915

  18. Attention Stabilizes Representations in the Human Hippocampus.

    PubMed

    Aly, Mariam; Turk-Browne, Nicholas B

    2016-02-01

    Attention and memory are intricately linked, but how attention modulates brain areas that subserve memory, such as the hippocampus, is unknown. We hypothesized that attention may stabilize patterns of activity in human hippocampus, resulting in distinct but reliable activity patterns for different attentional states. To test this prediction, we utilized high-resolution functional magnetic resonance imaging and a novel "art gallery" task. On each trial, participants viewed a room containing a painting, and searched a stream of rooms for a painting from the same artist (art state) or a room with the same layout (room state). Bottom-up stimulation was the same in both tasks, enabling the isolation of neural effects related to top-down attention. Multivariate analyses revealed greater pattern similarity in all hippocampal subfields for trials from the same, compared with different, attentional state. This stability was greater for the room than art state, was unrelated to univariate activity, and, in CA2/CA3/DG, was correlated with behavior. Attention therefore induces representational stability in the human hippocampus, resulting in distinct activity patterns for different attentional states. Modulation of hippocampal representational stability highlights the far-reaching influence of attention outside of sensory systems. PMID:25766839

  19. Proteome map of the human hippocampus.

    PubMed

    Edgar, P F; Douglas, J E; Knight, C; Cooper, G J; Faull, R L; Kydd, R

    1999-01-01

    The proteins expressed by a genome have been termed the proteome. By comparing the proteome of a disease-affected tissue with the proteome of an unaffected tissue it is possible to identify proteins that play a role in a disease process. The hippocampus is involved in the processing of short-term memory and is affected in Alzheimer's disease. Any comparative proteome analysis that can identify proteins important in a disease affecting the hippocampus requires the characterization of the normal hippocampal proteome. Therefore, we homogenised normal hippocampal tissue and separated the proteins by two-dimensional polyacrylamide gel electrophoresis (2DE). Seventy-two unique protein spots were collected from Coomassie blue-stained 2DE gels and subjected to in-gel digestion with trypsin, reversed-phase high-pressure liquid chromatography peptide separation, and N-terminal protein sequencing. Sufficient protein sequence was obtained to successfully characterize 66 of the 72 protein spots chosen (92%). Three of the 66 proteins were not present in any database (4.5%). The characterized proteins comprised two dominant functional groups, i.e., enzymes involved in intermediary cellular metabolism (40%), and proteins associated with the cytoskeleton (15%). The identity, molecular mass, isoelectric point, and relative concentration of the characterized proteins are described and constitute a partial proteome map of the normal human hippocampus. PMID:10641757

  20. Effect of hydroalcoholic extract of Anethum graveolens leaves on the dentate gyrus of the hippocampus in the epileptic mice: a histopathological and immunohistochemical study

    PubMed Central

    Golmohammadi, Rahim; Sabaghzadeh, Fatemeh; Mojadadi, Mohammad Shafi

    2016-01-01

    Anethum graveolens or Dill (local name: Shevid) belongs to the family of Apiaceae (Umbelliferae) and is used traditionally for the treatment of convulsion and diabetes in Iran. This study aimed to investigate the effect of hydroalcoholic extract of A. graveolens leaves on the histology of the dentate gyrus of the hippocampus in the epileptic mice kindled by Pentylenetetrazole (PTZ). In this experimental study, the epileptic BALB/c mice kindled by PTZ were randomly divided into four groups of 10 animals each. Three experimental groups received 250, 500 and 750 mg/kg/day of A. graveolens extract for 21 days. The control group received phosphate-buffered saline (PBS). After the treatment period, the mice were anesthetized, and their hippocampi were dissected for the histopathological analysis, and immunohistochemical analysis for caspase-3 activity. Histopathological examinations showed that the mean numbers of the healthy neuronal cells in the dentate gyrus of the mice received 500 mg/kg/day of A. graveolens extracts were significantly higher than those of the mice received 250 and 750 mg/kg/day of the extracts as well as the control group (P < 0.05 and P < 0.001, respectively). In addition, the results of immunohistochemical analysis revealed that in mice treated with 500 mg/kg/day of A. graveolens; the numbers of caspase-3-positive cells in the dentate gyrus were significantly lower than those of the two other test and the control groups. The findings of this study suggest that 500 mg/kg/day of the A. graveolens extract could have protective effect on the dentate gyrus of the hippocampus in the epileptic mice. PMID:27499792

  1. Effect of hydroalcoholic extract of Anethum graveolens leaves on the dentate gyrus of the hippocampus in the epileptic mice: a histopathological and immunohistochemical study.

    PubMed

    Golmohammadi, Rahim; Sabaghzadeh, Fatemeh; Mojadadi, Mohammad Shafi

    2016-01-01

    Anethum graveolens or Dill (local name: Shevid) belongs to the family of Apiaceae (Umbelliferae) and is used traditionally for the treatment of convulsion and diabetes in Iran. This study aimed to investigate the effect of hydroalcoholic extract of A. graveolens leaves on the histology of the dentate gyrus of the hippocampus in the epileptic mice kindled by Pentylenetetrazole (PTZ). In this experimental study, the epileptic BALB/c mice kindled by PTZ were randomly divided into four groups of 10 animals each. Three experimental groups received 250, 500 and 750 mg/kg/day of A. graveolens extract for 21 days. The control group received phosphate-buffered saline (PBS). After the treatment period, the mice were anesthetized, and their hippocampi were dissected for the histopathological analysis, and immunohistochemical analysis for caspase-3 activity. Histopathological examinations showed that the mean numbers of the healthy neuronal cells in the dentate gyrus of the mice received 500 mg/kg/day of A. graveolens extracts were significantly higher than those of the mice received 250 and 750 mg/kg/day of the extracts as well as the control group (P < 0.05 and P < 0.001, respectively). In addition, the results of immunohistochemical analysis revealed that in mice treated with 500 mg/kg/day of A. graveolens; the numbers of caspase-3-positive cells in the dentate gyrus were significantly lower than those of the two other test and the control groups. The findings of this study suggest that 500 mg/kg/day of the A. graveolens extract could have protective effect on the dentate gyrus of the hippocampus in the epileptic mice. PMID:27499792

  2. Measuring complexity and synchronization phenomena in the human epileptic brain

    NASA Astrophysics Data System (ADS)

    Lehnertz, Klaus

    2006-03-01

    The framework of the theory of nonlinear dynamics provides new concepts and powerful algorithms to study complicated dynamics such as the human electroencephalogram (EEG). Although different influencing factors render the use of nonlinear measures (such as measures for complexity, synchronization, or interdependencies) in a strict sense problematic, converging evidence from various investigations now indicates that nonlinear EEG analysis provides a means to reliably characterize different states of normal and pathological brain function and thus, promises to be important for clinical practice. This talk will focus on applications of nonlinear EEG analysis in epileptology. Epilepsy affects more than 50 million individuals worldwide - approximately 1 % of the world's population. The disease is characterized by a recurrent and sudden malfunction of the brain that is termed seizure. Epileptic seizures are the clinical manifestation of an excessive and hypersynchronous activity of neurons in the brain. It is assumed that seizure activity will be induced when a critical mass of neurons is progressively involved in closely time-linked high frequency discharging. Recent investigations of intracranially recorded EEG involving nonlinear time series analysis techniques indicate that this build up of a critical mass can indeed be tracked over time scales lasting minutes to hours. Future real-time analysis devices may enable both investigations of basic mechanisms leading to seizure initiation in humans and the development of adequate seizure warning and prevention strategies.

  3. Exploring human epileptic activity at the single-neuron level.

    PubMed

    Tankus, Ariel

    2016-05-01

    Today, localization of the seizure focus heavily relies on EEG monitoring (scalp or intracranial). However, current technology enables much finer resolutions. The activity of hundreds of single neurons in the human brain can now be simultaneously explored before, during, and after a seizure or in association with an interictal discharge. This technology opens up new horizons to understanding epilepsy at a completely new level. This review therefore begins with a brief description of the basis of the technology, the microelectrodes, and the setup for their implantation in patients with epilepsy. Using these electrodes, recent studies provide novel insights into both the time domain and firing patterns of epileptic activity of single neurons. In the time domain, seizure-related activity may occur even minutes before seizure onset (in its current, EEG-based definition). Seizure-related neuronal interactions exhibit complex heterogeneous dynamics. In the seizure-onset zone, changes in firing patterns correlate with cell loss; in the penumbra, neurons maintain their spike stereotypy during a seizure. Hence, investigation of the extracellular electrical activity is expected to provide a better understanding of the mechanisms underlying the disease; it may, in the future, serve for a more accurate localization of the seizure focus; and it may also be employed to predict the occurrence of seizures prior to their behavioral manifestation in order to administer automatic therapeutic interventions. PMID:26994366

  4. Musical Training Induces Functional Plasticity in Human Hippocampus

    PubMed Central

    Esposito, Fabrizio; di Salle, Francesco; Boller, Christian; Hilti, Caroline C.; Habermeyer, Benedikt; Scheffler, Klaus; Wetzel, Stephan; Seifritz, Erich; Cattapan-Ludewig, Katja

    2010-01-01

    Training can change the functional and structural organization of the brain, and animal models demonstrate that the hippocampus formation is particularly susceptible to training-related neuroplasticity. In humans, however, direct evidence for functional plasticity of the adult hippocampus induced by training is still missing. Here, we used musicians' brains as a model to test for plastic capabilities of the adult human hippocampus. By using functional magnetic resonance imaging optimized for the investigation of auditory processing, we examined brain responses induced by temporal novelty in otherwise isochronous sound patterns in musicians and musical laypersons, since the hippocampus has been suggested previously to be crucially involved in various forms of novelty detection. In the first cross-sectional experiment, we identified enhanced neural responses to temporal novelty in the anterior left hippocampus of professional musicians, pointing to expertise-related differences in hippocampal processing. In the second experiment, we evaluated neural responses to acoustic temporal novelty in a longitudinal approach to disentangle training-related changes from predispositional factors. For this purpose, we examined an independent sample of music academy students before and after two semesters of intensive aural skills training. After this training period, hippocampal responses to temporal novelty in sounds were enhanced in musical students, and statistical interaction analysis of brain activity changes over time suggests training rather than predisposition effects. Thus, our results provide direct evidence for functional changes of the adult hippocampus in humans related to musical training. PMID:20107063

  5. Preserved Hippocampal Glucose Metabolism on 18F-FDG PET after Transplantation of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells in Chronic Epileptic Rats

    PubMed Central

    Park, Ga Young; Lee, Eun Mi; Seo, Min-Soo; Seo, Yoo-Jin; Oh, Jungsu S.; Son, Woo-Chan; Kim, Ki Soo; Kim, Jae Seung; Kang, Kyung-Sun

    2015-01-01

    Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may be a promising modality for treating medial temporal lobe epilepsy. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a noninvasive method for monitoring in vivo glucose metabolism. We evaluated the efficacy of hUCB-MSCs transplantation in chronic epileptic rats using FDG-PET. Rats with recurrent seizures were randomly assigned into three groups: the stem cell treatment (SCT) group received hUCB-MSCs transplantation into the right hippocampus, the sham control (ShC) group received same procedure with saline, and the positive control (PC) group consisted of treatment-negative epileptic rats. Normal rats received hUCB-MSCs transplantation acted as the negative control (NC). FDG-PET was performed at pre-treatment baseline and 1- and 8-week posttreatment. Hippocampal volume was evaluated and histological examination was done. In the SCT group, bilateral hippocampi at 8-week after transplantation showed significantly higher glucose metabolism (0.990 ± 0.032) than the ShC (0.873 ± 0.087; P < 0.001) and PC groups (0.858 ± 0.093; P < 0.001). Histological examination resulted that the transplanted hUCB-MSCs survived in the ipsilateral hippocampus and migrated to the contralateral hippocampus but did not differentiate. In spite of successful engraftment, seizure frequency among the groups was not significantly different. Transplanted hUCB-MSCs can engraft and migrate, thereby partially restoring bilateral hippocampal glucose metabolism. The results suggest encouraging effect of hUCB-MSCs on restoring epileptic networks. PMID:26339161

  6. Knowledge-based localization of hippocampus in human brain MRI

    NASA Astrophysics Data System (ADS)

    Soltanian-Zadeh, Hamid; Siadat, Mohammad-Reza

    1999-05-01

    Hippocampus is an important structure of the human brain limbic system. The variations in the volume and architecture of this structure have been related to certain neurological diseases such as schizophrenia and epilepsy. This paper presents a two-stage method for localizing hippocampus in human brain MRI automatically. The first stage utilizes image processing techniques such as nonlinear filtering and histogram analysis to extract information from MRI. This stage generates binary images, locates lateral and third ventricles, and the inferior limit of Sylvian Fissure. The second stage uses a shell of expert system named VP-EXPERT to analyze the information extracted in the first stage. This stage utilizes absolute and relative spatial rules and spatial symmetry rules to locate the hippocampus. The system has been tested using MRI studies of six epilepsy patients. MRI data consisted of a total of 128 images. The system correctly identified all of the slices without hippocampus, and correctly localized hippocampus is about n 78% of the slices with hippocampus.

  7. A quantitative transcriptome reference map of the normal human hippocampus.

    PubMed

    Caracausi, Maria; Rigon, Vania; Piovesan, Allison; Strippoli, Pierluigi; Vitale, Lorenza; Pelleri, Maria Chiara

    2016-01-01

    We performed an innovative systematic meta-analysis of 41 gene expression profiles of normal human hippocampus to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 30,739 known mapped and the 16,258 uncharacterized (unmapped) transcripts. For this aim, we used the software called TRAM (Transcriptome Mapper), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the hippocampus with the whole brain transcriptome map to identify a typical expression pattern of this subregion compared with the whole organ. Finally, due to the fact that the hippocampus is one of the main brain region to be severely affected in trisomy 21 (the best known genetic cause of intellectual disability), a particular attention was paid to the expression of chromosome 21 (chr21) genes. Data were downloaded from microarray databases, processed, and analyzed using TRAM software. Among the main findings, the most over-expressed loci in the hippocampus are the expressed sequence tag cluster Hs.732685 and the member of the calmodulin gene family CALM2. The tubulin folding cofactor B (TBCB) gene is the best gene at behaving like a housekeeping gene. The hippocampus vs. the whole brain differential transcriptome map shows the over-expression of LINC00114, a long non-coding RNA mapped on chr21. The hippocampus transcriptome map was validated in vitro by assaying gene expression through several magnitude orders by "Real-Time" reverse transcription polymerase chain reaction (RT-PCR). The highly significant agreement between in silico and experimental data suggested that our transcriptome map may be a useful quantitative reference benchmark for gene expression studies related to human hippocampus. Furthermore, our analysis yielded biological insights about those genes that have an intrinsic over-/under-expression in the hippocampus. PMID

  8. Nonlinear times series analysis of epileptic human electroencephalogram (EEG)

    NASA Astrophysics Data System (ADS)

    Li, Dingzhou

    The problem of seizure anticipation in patients with epilepsy has attracted significant attention in the past few years. In this paper we discuss two approaches, using methods of nonlinear time series analysis applied to scalp electrode recordings, which is able to distinguish between epochs temporally distant from and just prior to, the onset of a seizure in patients with temporal lobe epilepsy. First we describe a method involving a comparison of recordings taken from electrodes adjacent to and remote from the site of the seizure focus. In particular, we define a nonlinear quantity which we call marginal predictability. This quantity is computed using data from remote and from adjacent electrodes. We find that the difference between the marginal predictabilities computed for the remote and adjacent electrodes decreases several tens of minutes prior to seizure onset, compared to its value interictally. We also show that these difl'crcnc es of marginal predictability intervals are independent of the behavior state of the patient. Next we examine the please coherence between different electrodes both in the long-range and the short-range. When time is distant from seizure onsets ("interictally"), epileptic patients have lower long-range phase coherence in the delta (1-4Hz) and beta (18-30Hz) frequency band compared to nonepileptic subjects. When seizures approach (''preictally"), we observe an increase in phase coherence in the beta band. However, interictally there is no difference in short-range phase coherence between this cohort of patients and non-epileptic subjects. Preictally short-range phase coherence also increases in the alpha (10-13Hz) and the beta band. Next we apply the quantity marginal predictability on the phase difference time series. Such marginal predictabilities are lower in the patients than in the non-epileptic subjects. However, when seizure approaches, the former moves asymptotically towards the latter.

  9. Patterns of human local cerebral glucose metabolism during epileptic seizures

    SciTech Connect

    Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.

    1982-10-01

    Ictal patterns of local cerebral metabolic rate have been studied in epileptic patients by positron computed tomography with /sup 18/F-labeled 2-fluoro-2-deoxy-D-glucose. Partial seizures were associated with activation of anatomic structures unique to each patient studied. Ictal increases and decreases in local cerebral metabolism were observed. Scans performed during generalized convulsions induced by electroshock demonstrated a diffuse ictal increase and postictal decrease in cerebral metabolism. Petit mal absences were associated with a diffuse increase in cerebral metabolic rate. The ictal fluorodeoxyglucose patterns obtained from patients do not resemble autoradiographic patterns obtained from common experimental animal models of epilepsy.

  10. Two different mechanisms associated with ripple-like oscillations (100-250 Hz) in the human epileptic subiculum in vitro

    PubMed Central

    Alvarado-Rojas, C; Huberfeld, G; Baulac, M; Clemenceau, S; Charpier, S; Miles, R; Menendez de la Prida, L; Le Van Quyen, M

    2015-01-01

    Transient high-frequency oscillations (150-600 Hz) in local field potential generated by human hippocampal and parahippocampal areas have been related to both physiological and pathological processes. The cellular basis and effects of normal and abnormal forms of high-frequency oscillations (HFO) has been controversial. Here, we searched for HFOs in slices of the subiculum prepared from human hippocampal tissue resected for treatment of pharmacoresistant epilepsy. HFOs occurred spontaneously in extracellular field potentials during interictal discharges (IID) and also during pharmacologically induced preictal discharges (PID) preceding ictal-like events. While most of these events might be considered pathological since they invaded the fast ripple band (>250 Hz), others were spectrally similar to physiological ripples (150-250 Hz). Do similar cellular mechanisms underly IID-ripples and PID-ripples? Are ripple-like oscillations a valid proxy of epileptogenesis in human TLE? With combined intra- or juxta-cellular and extracellular recordings, we showed that, despite overlapping spectral components, ripple-like IID and PID oscillations were associated with different cellular and synaptic mechanisms. IID-ripples were associated with rhythmic GABAergic and glutamatergic synaptic potentials with moderate neuronal firing. In contrast, PID-ripples were associated with depolarizing synaptic inputs frequently reaching the threshold for bursting in most cells. Thus ripple-like oscillations (100-250 Hz) in the human epileptic hippocampus are associated with different mechanisms for synchrony reflecting distinct dynamic changes in inhibition and excitation during interictal and pre-ictal states. PMID:25448920

  11. Correlation Between IL-10 and microRNA-187 Expression in Epileptic Rat Hippocampus and Patients with Temporal Lobe Epilepsy

    PubMed Central

    Alsharafi, Walid A.; Xiao, Bo; Abuhamed, Mutasem M.; Bi, Fang-Fang; Luo, Zhao-Hui

    2015-01-01

    Accumulating evidence is emerging that microRNAs (miRNAs) are key regulators in controlling neuroinflammatory responses that are known to play a potential role in the pathogenesis of temporal lobe epilepsy (TLE). The aim of the present study was to investigate the dynamic expression pattern of interleukin (IL)-10 as an anti-inflammatory cytokine and miR-187 as a post-transcriptional inflammation-related miRNA in the hippocampus of a rat model of status epilepticus (SE) and patients with TLE. We performed a real-time quantitative PCR and western blot on rat hippocampus 2 h, 7 days, 21 days and 60 days following pilocarpine-induced SE, and on hippocampus obtained from TLE patients and normal controls. To detect the relationship between IL-10 and miR-187 on neurons, lipopolysaccharide (LPS) and IL-10-stimulated neurons were performed. Furthermore, we identified the effect of antagonizing miR-187 by its antagomir on IL-10 secretion. Here, we reported that IL-10 secretion and miR-187 expression levels are inversely correlated after SE. In patients with TLE, the expression of IL-10 was also significantly upregulated, whereas miR-187 expression was significantly downregulated. Moreover, miR-187 expression was significantly reduced following IL-10 stimulation in an IL-10–dependent manner. On the other hand, antagonizing miR-187 promoted the production of IL-10 in hippocampal tissues of rat model of SE. Our findings demonstrate a critical role of miR-187 in the physiological regulation of IL-10 anti-inflammatory responses and elucidate the role of neuroinflammation in the pathogenesis of TLE. Therefore, modulation of the IL-10 / miR-187 axis may be a new therapeutic approach for TLE. PMID:26696826

  12. Grouping Pentylenetetrazol-Induced Epileptic Rats According to Memory Impairment and MicroRNA Expression Profiles in the Hippocampus

    PubMed Central

    Liu, Xixia; Wu, Yuan; Huang, Qi; Zou, Donghua; Qin, Weihan; Chen, Zhen

    2015-01-01

    Previous studies have demonstrated a close relationship between abnormal regulation of microRNA (miRNA) and various types of diseases, including epilepsy and other neurological disorders of memory. However, the role of miRNA in the memory impairment observed in epilepsy remains unknown. In this study, a model of temporal lobe epilepsy (TLE) was induced via pentylenetetrazol (PTZ) kindling in Sprague-Dawley rats. First, the TLE rats were subjected to Morris water maze to identify those with memory impairment (TLE-MI) compared with TLE control rats (TLE-C), which presented normal memory. Both groups were analyzed to detect dysregulated miRNAs in the hippocampus; four up-regulated miRNAs (miR-34c, miR-374, miR-181a, and miR-let-7c-1) and seven down-regulated miRNAs (miR-1188, miR-770-5p, miR-127-5p, miR-375, miR-331, miR-873-5p, and miR-328a) were found. Some of the dysregulated miRNAs (miR-34c, miR-1188a, miR-328a, and miR-331) were confirmed using qRT-PCR, and their blood expression patterns were identical to those of their counterparts in the rat hippocampus. The targets of these dysregulated miRNAs and other potentially enriched biological signaling pathways were analyzed using bioinformatics. Following these results, the MAPK, apoptosis and hippocampal signaling pathways might be involved in the molecular mechanisms underlying the memory disorders of TLE. PMID:25962166

  13. BDNF modulates GABAA receptors microtransplanted from the human epileptic brain to Xenopus oocytes

    PubMed Central

    Palma, E.; Torchia, G.; Limatola, C.; Trettel, F.; Arcella, A.; Cantore, G.; Di Gennaro, G.; Manfredi, M.; Esposito, V.; Quarato, P. P.; Miledi, R.; Eusebi, F.

    2005-01-01

    Cell membranes isolated from brain tissues, obtained surgically from six patients afflicted with drug-resistant temporal lobe epilepsy and from one nonepileptic patient afflicted with a cerebral oligodendroglioma, were injected into frog oocytes. By using this approach, the oocytes acquire human GABAA receptors, and we have shown previously that the “epileptic receptors” (receptors transplanted from epileptic brains) display a marked run-down during repetitive applications of GABA. It was found that exposure to the neurotrophin BDNF increased the amplitude of the “GABA currents” (currents elicited by GABA) generated by the epileptic receptors and decreased their run-down; both events being blocked by K252A, a neurotrophin tyrosine kinase receptor B inhibitor. These effects of BDNF were not mimicked by nerve growth factor. In contrast, the GABAA receptors transplanted from the nonepileptic human hippocampal uncus (obtained during surgical resection as part of the nontumoral tissue from the oligodendroglioma margins) or receptors expressed by injecting rat recombinant α1β2γ2 GABAA receptor subunit cDNAs generated GABA currents whose time-course and run-down were not altered by BDNF. Loading the oocytes with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetate-acetoxymethyl ester (BAPTA-AM), or treating them with Rp-8-Br-cAMP, an inhibitor of the cAMP-dependent PKA, did not alter the GABA currents. However, staurosporine (a broad spectrum PK inhibitor), bisindolylmaleimide I (a PKC inhibitor), and U73122 (a phospholipase C inhibitor) blocked the BDNF-induced effects on the epileptic GABA currents. Our results indicate that BDNF potentiates the epileptic GABAA currents and antagonizes their use-dependent run-down, thus strengthening GABAergic inhibition, probably by means of activation of tyrosine kinase receptor B receptors and of both PLC and PKC. PMID:15665077

  14. Proteogenomics of the human hippocampus: The road ahead.

    PubMed

    Kang, Myoung-Goo; Byun, Kyunghee; Kim, Jae Ho; Park, Nam Hyun; Heinsen, Helmut; Ravid, Rivka; Steinbusch, Harry W; Lee, Bonghee; Park, Young Mok

    2015-07-01

    The hippocampus is one of the most essential components of the human brain and plays an important role in learning and memory. The hippocampus has drawn great attention from scientists and clinicians due to its clinical importance in diseases such as Alzheimer's disease (AD), non-AD dementia, and epilepsy. Understanding the function of the hippocampus and related disease mechanisms requires comprehensive knowledge of the orchestration of the genome, epigenome, transcriptome, proteome, and post-translational modifications (PTMs) of proteins. The past decade has seen remarkable advances in the high-throughput sequencing techniques that are collectively called next generation sequencing (NGS). NGS enables the precise analysis of gene expression profiles in cells and tissues, allowing powerful and more feasible integration of expression data from the gene level to the protein level, even allowing "-omic" level assessment of PTMs. In addition, improved bioinformatics algorithms coupled with NGS technology are finally opening a new era for scientists to discover previously unidentified and elusive proteins. In the present review, we will focus mainly on the proteomics of the human hippocampus with an emphasis on the integrated analysis of genomics, epigenomics, transcriptomics, and proteomics. Finally, we will discuss our perspectives on the potential and future of proteomics in the field of hippocampal biology. This article is part of a Special Issue entitled: Neuroproteomics: Applications in Neuroscience and Neurology. PMID:25770686

  15. Decoding individual episodic memory traces in the human hippocampus.

    PubMed

    Chadwick, Martin J; Hassabis, Demis; Weiskopf, Nikolaus; Maguire, Eleanor A

    2010-03-23

    In recent years, multivariate pattern analyses have been performed on functional magnetic resonance imaging (fMRI) data, permitting prediction of mental states from local patterns of blood oxygen-level-dependent (BOLD) signal across voxels. We previously demonstrated that it is possible to predict the position of individuals in a virtual-reality environment from the pattern of activity across voxels in the hippocampus. Although this shows that spatial memories can be decoded, substantially more challenging, and arguably only possible to investigate in humans, is whether it is feasible to predict which complex everyday experience, or episodic memory, a person is recalling. Here we document for the first time that traces of individual rich episodic memories are detectable and distinguishable solely from the pattern of fMRI BOLD signals across voxels in the human hippocampus. In so doing, we uncovered a possible functional topography in the hippocampus, with preferential episodic processing by some hippocampal regions over others. Moreover, our results imply that the neuronal traces of episodic memories are stable (and thus predictable) even over many re-activations. Finally, our data provide further evidence for functional differentiation within the medial temporal lobe, in that we show the hippocampus contains significantly more episodic information than adjacent structures. PMID:20226665

  16. Voxel-based morphometry in epileptic baboons: Parallels to human juvenile myoclonic epilepsy.

    PubMed

    Szabó, C Ákos; Salinas, Felipe S

    2016-08-01

    The epileptic baboon represents a natural model for genetic generalized epilepsy (GGE), closely resembling juvenile myoclonic epilepsy (JME). Due to functional neuroimaging and pathological differences between epileptic (SZ+) and asymptomatic control (CTL) baboons, we expected structural differences in gray matter concentration (GMC) using voxel-based morphometry (VBM). Standard anatomical (MP-RAGE) MRI scans using a 3T Siemens TIM Trio (Siemens, Erlangen, Germany) were available in 107 baboons (67 females; mean age 16±6years) with documented clinical histories and scalp-electroencephalography (EEG) results. For neuroimaging, baboons were anesthetized with isoflurane 1% (1-1.5 MAC) and paralyzed with vecuronium (0.1-0.3mg/kg). Data processing and analysis were performed using FSL's VBM toolbox. GMC was compared between CTL and SZ+ baboons, epileptic baboons with interictal epileptic discharges on scalp EEG (SZ+/IED+), asymptomatic baboons with abnormal EEGs (SZ-/IED+), and IED+ baboons with (IED+/PS+) and without (IED+/PS-) photosensitivity, and the subgroups amongst themselves. Age and gender related changes in gray matter volumes were also included as confound regressors in the VBM analyses of each animal group. Significant increases in GMC were noted in the SZ+/IED+ subgroup compared to the CTL group, including bilaterally in the frontopolar, orbitofrontal and anterolateral temporal cortices, while decreases in GMC were noted in the right more than left primary visual cortices and in the specific nuclei of the thalamus, including reticular, anterior and medial dorsal nuclei. No significant differences were noted otherwise, except that SZ+/IED+ baboons demonstrated increased GMC in the globus pallidae bilaterally compared to the SZ-/IED+ group. Similar to human studies of JME, the epileptic baboons demonstrated GMC decreases in the thalami and occipital cortices, suggesting secondary injury due to chronic epilepsy. Cortical GMC, on the other hand, was increased

  17. Prospective representation of navigational goals in the human hippocampus.

    PubMed

    Brown, Thackery I; Carr, Valerie A; LaRocque, Karen F; Favila, Serra E; Gordon, Alan M; Bowles, Ben; Bailenson, Jeremy N; Wagner, Anthony D

    2016-06-10

    Mental representation of the future is a fundamental component of goal-directed behavior. Computational and animal models highlight prospective spatial coding in the hippocampus, mediated by interactions with the prefrontal cortex, as a putative mechanism for simulating future events. Using whole-brain high-resolution functional magnetic resonance imaging and multi-voxel pattern classification, we tested whether the human hippocampus and interrelated cortical structures support prospective representation of navigational goals. Results demonstrated that hippocampal activity patterns code for future goals to which participants subsequently navigate, as well as for intervening locations along the route, consistent with trajectory-specific simulation. The strength of hippocampal goal representations covaried with goal-related coding in the prefrontal, medial temporal, and medial parietal cortex. Collectively, these data indicate that a hippocampal-cortical network supports prospective simulation of navigational events during goal-directed planning. PMID:27284194

  18. Developing an Animal Model of Human Amnesia: The Role of the Hippocampus

    ERIC Educational Resources Information Center

    Kesner, Raymond P.; Goodrich-Hunsaker, Naomi J.

    2010-01-01

    This review summarizes a series of experiments aimed at answering the question whether the hippocampus in rats can serve as an animal model of amnesia. It is recognized that a comparison of the functions of the rat hippocampus with human hippocampus is difficult, because of differences in methodology, differences in complexity of life experiences,…

  19. Potassium Channels and Human Epileptic Phenotypes: An Updated Overview

    PubMed Central

    Villa, Chiara; Combi, Romina

    2016-01-01

    Potassium (K+) channels are expressed in almost every cells and are ubiquitous in neuronal and glial cell membranes. These channels have been implicated in different disorders, in particular in epilepsy. K+ channel diversity depends on the presence in the human genome of a large number of genes either encoding pore-forming or accessory subunits. More than 80 genes encoding the K+ channels were cloned and they represent the largest group of ion channels regulating the electrical activity of cells in different tissues, including the brain. It is therefore not surprising that mutations in these genes lead to K+ channels dysfunctions linked to inherited epilepsy in humans and non-human model animals. This article reviews genetic and molecular progresses in exploring the pathogenesis of different human epilepsies, with special emphasis on the role of K+ channels in monogenic forms. PMID:27064559

  20. Potassium Channels and Human Epileptic Phenotypes: An Updated Overview.

    PubMed

    Villa, Chiara; Combi, Romina

    2016-01-01

    Potassium (K(+)) channels are expressed in almost every cells and are ubiquitous in neuronal and glial cell membranes. These channels have been implicated in different disorders, in particular in epilepsy. K(+) channel diversity depends on the presence in the human genome of a large number of genes either encoding pore-forming or accessory subunits. More than 80 genes encoding the K(+) channels were cloned and they represent the largest group of ion channels regulating the electrical activity of cells in different tissues, including the brain. It is therefore not surprising that mutations in these genes lead to K(+) channels dysfunctions linked to inherited epilepsy in humans and non-human model animals. This article reviews genetic and molecular progresses in exploring the pathogenesis of different human epilepsies, with special emphasis on the role of K(+) channels in monogenic forms. PMID:27064559

  1. Dopamine regulates stimulus generalization in the human hippocampus

    PubMed Central

    Kahnt, Thorsten; Tobler, Philippe N

    2016-01-01

    The ability to generalize previously learned information to novel situations is fundamental for adaptive behavior. However, too wide or too narrow generalization is linked to neuropsychiatric disorders. Previous research suggests that interactions between the dopaminergic system and the hippocampus may play a role in generalization, but whether and how the degree of generalization can be modulated via these pathways is currently unknown. Here, we addressed this question in humans using pharmacology, functional magnetic resonance imaging, and computational modeling. Blocking dopamine D2-receptors (D2R) altered generalization behavior as revealed by an increased kurtosis of the generalization gradient, and a decreased width of model-derived generalization parameters. Moreover, D2R-blockade modulated similarity-based responses in the hippocampus and decreased midbrain-hippocampal connectivity, which in turn correlated with individual differences in generalization. These results suggest that dopaminergic activity in the hippocampus may relate to the degree of generalization and highlight a potential target for treatment. DOI: http://dx.doi.org/10.7554/eLife.12678.001 PMID:26830462

  2. Modeling network correlations in cortical tissue from juvenile human epileptics

    NASA Astrophysics Data System (ADS)

    Hobbs, Jonathan Paul

    Models of neural tissue can make predictions about a real neural network, but these predictions rely on the data to determine parameters. Hence, the model is only as good as the data. I collected in vitro data removed from juvenile humans with refractory epilepsy, and found human-specific spatial and temporal dynamics that are not found in rats. I will first describe the general characteristics of the human data in comparison with rat data, and my attempts to model these differences with three popular models of neural networks: branching, pair-wise maximum entropy, and a forest fire model. I will describe three key discoveries from this exploration: first, spatial dynamics are more easily satisfied than temporal in both the rat and human tissue, second temporal correlations are not captured by the branching or the maximum entropy model, and thirdly, strong temporal correlations can be accounted for with the addition of a parameter in the forest fire model. Finally I will suggest new questions that this research has revealed about human tissue, and models of neural networks.

  3. Predicting novel histopathological microlesions in human epileptic brain through transcriptional clustering

    PubMed Central

    Dachet, Fabien; Bagla, Shruti; Keren-Aviram, Gal; Morton, Andrew; Balan, Karina; Saadat, Laleh; Valyi-Nagy, Tibor; Kupsky, William; Song, Fei; Dratz, Edward; Loeb, Jeffrey A.

    2015-01-01

    Although epilepsy is associated with a variety of abnormalities, exactly why some brain regions produce seizures and others do not is not known. We developed a method to identify cellular changes in human epileptic neocortex using transcriptional clustering. A paired analysis of high and low spiking tissues recorded in vivo from 15 patients predicted 11 cell-specific changes together with their ‘cellular interactome’. These predictions were validated histologically revealing millimetre-sized ‘microlesions’ together with a global increase in vascularity and microglia. Microlesions were easily identified in deeper cortical layers using the neuronal marker NeuN, showed a marked reduction in neuronal processes, and were associated with nearby activation of MAPK/CREB signalling, a marker of epileptic activity, in superficial layers. Microlesions constitute a common, undiscovered layer-specific abnormality of neuronal connectivity in human neocortex that may be responsible for many ‘non-lesional’ forms of epilepsy. The transcriptional clustering approach used here could be applied more broadly to predict cellular differences in other brain and complex tissue disorders. PMID:25516101

  4. Multi-electrode Array Recordings of Human Epileptic Postoperative Cortical Tissue

    PubMed Central

    Dossi, Elena; Blauwblomme, Thomas; Nabbout, Rima; Huberfeld, Gilles; Rouach, Nathalie

    2014-01-01

    Epilepsy, affecting about 1% of the population, comprises a group of neurological disorders characterized by the periodic occurrence of seizures, which disrupt normal brain function. Despite treatment with currently available antiepileptic drugs targeting neuronal functions, one third of patients with epilepsy are pharmacoresistant. In this condition, surgical resection of the brain area generating seizures remains the only alternative treatment. Studying human epileptic tissues has contributed to understand new epileptogenic mechanisms during the last 10 years. Indeed, these tissues generate spontaneous interictal epileptic discharges as well as pharmacologically-induced ictal events which can be recorded with classical electrophysiology techniques. Remarkably, multi-electrode arrays (MEAs), which are microfabricated devices embedding an array of spatially arranged microelectrodes, provide the unique opportunity to simultaneously stimulate and record field potentials, as well as action potentials of multiple neurons from different areas of the tissue. Thus MEAs recordings offer an excellent approach to study the spatio-temporal patterns of spontaneous interictal and evoked seizure-like events and the mechanisms underlying seizure onset and propagation. Here we describe how to prepare human cortical slices from surgically resected tissue and to record with MEAs interictal and ictal-like events ex vivo. PMID:25407747

  5. Interictal high-frequency oscillations (80-500 Hz) in the human epileptic brain: entorhinal cortex.

    PubMed

    Bragin, Anatol; Wilson, Charles L; Staba, Richard J; Reddick, Mark; Fried, Itzhak; Engel, Jerome

    2002-10-01

    Unique high-frequency oscillations of 250 to 500 Hz, termed fast ripples, have been identified in seizure-generating limbic areas in rats made epileptic by intrahippocampal injection of kainic acid, and in patients with mesial temporal lobe epilepsy. In the rat, fast ripples clearly are generated by a different neuronal population than normally occurring endogenous ripple oscillations (100-200 Hz), but this distinction has not been previously evaluated in humans. The characteristics of oscillations in the ripple and fast ripple frequency bands were compared in the entorhinal cortex of patients with mesial temporal lobe epilepsy using local field potential and unit recordings from chronically implanted bundles of eight microelectrodes with tips spaced 500 microm apart. The results showed that ripple oscillations possessed different voltage versus depth profiles compared with fast ripple oscillations. Fast ripple oscillations usually demonstrated a reversal of polarity in the middle layers of entorhinal cortex, whereas ripple oscillations rarely showed reversals across entorhinal cortex layers. There was no significant difference in the amplitude distributions of ripple and fast ripple oscillations. Furthermore, multiunit synchronization was significantly increased during fast ripple oscillations compared with ripple oscillations (p < 0.001). These data recorded from the mesial temporal lobe of epileptic patients suggest that the cellular networks underlying fast ripple generation are more localized than those involved in the generation of normally occurring ripple oscillations. Results from this study are consistent with previous studies in the intrahippocampal kainic acid rat model of chronic epilepsy that provide evidence supporting the view that fast ripples in the human brain reflect localized pathological events related to epileptogenesis. PMID:12325068

  6. Expression of human epileptic temporal lobe neurotransmitter receptors in Xenopus oocytes: An innovative approach to study epilepsy.

    PubMed

    Palma, Eleonora; Esposito, Vincenzo; Mileo, Anna Maria; Di Gennaro, Giancarlo; Quarato, Pierpaolo; Giangaspero, Felice; Scoppetta, Ciriaco; Onorati, Paolo; Trettel, Flavia; Miledi, Ricardo; Eusebi, Fabrizio

    2002-11-12

    Poly(A(+)) RNA was extracted from the temporal lobe (TL) of medically intractable epileptic patients which underwent surgical TL resection. Injection of this mRNA into Xenopus oocytes led to the expression of ionotropic receptors for gamma-aminobutyric acid (GABA), kainate (KAI) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Membrane currents elicited by GABA inverted polarity at -15 mV, close to the oocyte's chloride equilibrium potential, were inhibited by bicuculline, and were potentiated by pentobarbital and flunitrazepam. These basic characteristics were also displayed by GABA currents elicited in oocytes injected with mRNAs isolated from human TL glioma (TLG) or from mouse TL. However, the GABA receptors expressed by the epileptic TL mRNA exhibited some unusual properties, consisting in a rapid current run-down after repetitive GABA applications and a large EC(50) (125 microM). AMPA alone evoked very small or nil currents, whereas KAI induced larger currents. Nevertheless, upon cyclothiazide treatment, AMPA elicited substantial currents that, like the KAI currents, were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Furthermore, the glutamate receptor 5 (GluR5) agonist, ATPA, failed to evoke an obvious current although both RT-PCR and Western blot analyses showed GluR5 expression in the epileptic TL. Oocytes injected with mouse TL or human TLG mRNAs generated KAI and AMPA currents similar to those evoked in oocytes injected with epileptic TL mRNA but, in contrast to these, the mouse TL and human TLG oocytes were also responsive to ATPA. Our findings are in accord with the concept that both a depression of GABA inhibition and a dysfunction of the KAI-receptor system maintain a high neuronal excitability that results in epileptic seizures. PMID:12409614

  7. Expression of human epileptic temporal lobe neurotransmitter receptors in Xenopus oocytes: An innovative approach to study epilepsy

    PubMed Central

    Palma, Eleonora; Esposito, Vincenzo; Mileo, Anna Maria; Di Gennaro, Giancarlo; Quarato, Pierpaolo; Giangaspero, Felice; Scoppetta, Ciriaco; Onorati, Paolo; Trettel, Flavia; Miledi, Ricardo; Eusebi, Fabrizio

    2002-01-01

    Poly(A+) RNA was extracted from the temporal lobe (TL) of medically intractable epileptic patients which underwent surgical TL resection. Injection of this mRNA into Xenopus oocytes led to the expression of ionotropic receptors for γ-aminobutyric acid (GABA), kainate (KAI) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Membrane currents elicited by GABA inverted polarity at −15 mV, close to the oocyte's chloride equilibrium potential, were inhibited by bicuculline, and were potentiated by pentobarbital and flunitrazepam. These basic characteristics were also displayed by GABA currents elicited in oocytes injected with mRNAs isolated from human TL glioma (TLG) or from mouse TL. However, the GABA receptors expressed by the epileptic TL mRNA exhibited some unusual properties, consisting in a rapid current run-down after repetitive GABA applications and a large EC50 (125 μM). AMPA alone evoked very small or nil currents, whereas KAI induced larger currents. Nevertheless, upon cyclothiazide treatment, AMPA elicited substantial currents that, like the KAI currents, were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Furthermore, the glutamate receptor 5 (GluR5) agonist, ATPA, failed to evoke an obvious current although both RT-PCR and Western blot analyses showed GluR5 expression in the epileptic TL. Oocytes injected with mouse TL or human TLG mRNAs generated KAI and AMPA currents similar to those evoked in oocytes injected with epileptic TL mRNA but, in contrast to these, the mouse TL and human TLG oocytes were also responsive to ATPA. Our findings are in accord with the concept that both a depression of GABA inhibition and a dysfunction of the KAI-receptor system maintain a high neuronal excitability that results in epileptic seizures. PMID:12409614

  8. Domoic Acid Epileptic Disease

    PubMed Central

    Ramsdell, John S.; Gulland, Frances M.

    2014-01-01

    Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a breadth of insight into clinical presentations, unusual behaviors, brain pathology, and epidemiology. A rat model that replicates key observations of the chronic epileptic syndrome in sea lions has been applied to identify the progression of the epileptic disease state, its relationship to behavioral manifestations, and to define the neural systems involved in these behavioral disorders. Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. We discuss causative mechanisms and neural underpinnings of disease maturation revealed by the rat model to present the concept for olfactory origin of an epileptic disease; triggered in dendodendritic synapases of the olfactory bulb and maturing in the olfactory cortex. We conclude with updated information on populations at risk, medical diagnosis, treatment, and prognosis. PMID:24663110

  9. Domoic acid epileptic disease.

    PubMed

    Ramsdell, John S; Gulland, Frances M

    2014-03-01

    Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a breadth of insight into clinical presentations, unusual behaviors, brain pathology, and epidemiology. A rat model that replicates key observations of the chronic epileptic syndrome in sea lions has been applied to identify the progression of the epileptic disease state, its relationship to behavioral manifestations, and to define the neural systems involved in these behavioral disorders. Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. We discuss causative mechanisms and neural underpinnings of disease maturation revealed by the rat model to present the concept for olfactory origin of an epileptic disease; triggered in dendodendritic synapases of the olfactory bulb and maturing in the olfactory cortex. We conclude with updated information on populations at risk, medical diagnosis, treatment, and prognosis. PMID:24663110

  10. Neuronal synchrony in relation to burst discharge in epileptic human temporal lobes.

    PubMed

    Colder, B W; Wilson, C L; Frysinger, R C; Chao, L C; Harper, R M; Engel, J

    1996-06-01

    1. Synchronous interactions between neurons in mesial temporal structures of patients with complex partial seizures were studied using cross-correlation analyses. We recorded spontaneous activity from 293 neurons in 24 patients during the interictal state. Patients had depth microelectrodes chronically implanted in amygdala, hippocampal formation, and parahippocampal gyrus to record epileptic activity. One hundred twenty-five cells were recorded from the temporal lobe commonly initiating seizures (ipsilateral temporal lobe), and 168 cells from the contralateral temporal lobe. Eight hundred forty-three cross-correlograms were constructed between all pairs of simultaneously recorded neurons. Cross-correlogram peaks or troughs that exceeded confidence limits within 200 ms of the origin were considered evidence of synchronous neuronal interaction. 2. Synchronous neuronal interactions were observed in 223 of 843 cross-correlograms. Eighty-six percent of these 223 cross-correlograms showed significant central peaks (peak interactions), suggesting excitatory interactions, whereas the remainder displayed significant central troughs (trough interactions), suggesting inhibitory interactions. 3. Cross-correlograms constructed using cells from the ipsilateral temporal lobe (ipsilateral cross-correlograms) were more likely to display significant central troughs (14/262) than cross-correlograms constructed using cells from the contralateral temporal lobe (6/376; contralateral cross-correlograms). Similarly, cross-correlograms constructed using one cell from each hemisphere (11/205; bilateral cross-correlograms) were also more likely to display significant central troughs (trough interactions) than contralateral cross-correlograms. Both ipsilateral (77/262) and contralateral cross-correlograms (102/376) were more likely to display significant central peaks (peak interactions) than bilateral cross-correlograms (13/205). 4. Cells from different structures in the ipsilateral

  11. Automated segmentation of the human hippocampus along its longitudinal axis.

    PubMed

    Lerma-Usabiaga, Garikoitz; Iglesias, Juan Eugenio; Insausti, Ricardo; Greve, Douglas N; Paz-Alonso, Pedro M

    2016-09-01

    The human hippocampal formation is a crucial brain structure for memory and cognitive function that is closely related to other subcortical and cortical brain regions. Recent neuroimaging studies have revealed differences along the hippocampal longitudinal axis in terms of structure, connectivity, and function, stressing the importance of improving the reliability of the available segmentation methods that are typically used to divide the hippocampus into its anterior and posterior parts. However, current segmentation conventions present two main sources of variability related to manual operations intended to correct in-scanner head position across subjects and the selection of dividing planes along the longitudinal axis. Here, our aim was twofold: (1) to characterize inter- and intra-rater variability associated with these manual operations and compare manual (landmark based) and automatic (percentage based) hippocampal anterior-posterior segmentation procedures; and (2) to propose and test automated rotation methods based on approximating the hippocampal longitudinal axis to a straight line (estimated with principal component analysis, PCA) or a quadratic Bézier curve (fitted with numerical methods); as well as an automated anterior-posterior hippocampal segmentation procedure based on the percentage-based method. Our results reveal that automated rotation and segmentation procedures, used in combination or independently, minimize inconsistencies generated by the accumulation of manual operations while providing higher statistical power to detect well-known effects. A Matlab-based implementation of these procedures is made publicly available to the research community. Hum Brain Mapp 37:3353-3367, 2016. © 2016 Wiley Periodicals, Inc. PMID:27159325

  12. Early Detection of Human Epileptic Seizures Based on Intracortical Local Field Potentials.

    PubMed

    Park, Yun S; Hochberg, Leigh R; Eskandar, Emad N; Cash, Sydney S; Truccolo, Wilson

    2013-01-01

    The unpredictability of re-occurring seizures dramatically impacts the quality of life and autonomy of people with epilepsy. Reliable early seizure detection could open new therapeutic possibilities and thus substantially improve quality of life and autonomy. Though many seizure detection studies have shown the potential of scalp electroencephalogram (EEG) and intracranial EEG (iEEG) signals, reliable early detection of human seizures remains elusive in practice. Here, we examined the use of intracortical local field potentials (LFPs) recorded from 4×4-mm(2) 96-microelectrode arrays (MEA) for early detection of human epileptic seizures. We adopted a framework consisting of (1) sampling of intracortical LFPs; (2) denoising of LFPs with the Kalman filter; (3) spectral power estimation in specific frequency bands using 1-sec moving time windows; (4) extraction of statistical features, such as the mean, variance, and Fano factor (calculated across channels) of the power in each frequency band; and (5) cost-sensitive support vector machine (SVM) classification of ictal and interictal samples. We tested the framework in one-participant dataset, including 4 seizures and corresponding interictal recordings preceding each seizure. The participant was a 52-year-old woman suffering from complex partial seizures. LFPs were recorded from an MEA implanted in the participant's left middle temporal gyrus. In this participant, spectral power in 0.3-10 Hz, 20-55 Hz, and 125-250 Hz changed significantly between ictal and interictal epochs. The examined seizure detection framework provided an event-wise sensitivity of 100% (4/4) and only one 20-sec-long false positive event in interictal recordings (likely an undetected subclinical event under further visual inspection), and a detection latency of 4.35 ± 2.21 sec (mean ± std) with respect to iEEG-identified seizure onsets. These preliminary results indicate that intracortical MEA recordings may provide key signals to quickly and

  13. Adenosine receptor antagonists alter the stability of human epileptic GABAA receptors

    PubMed Central

    Roseti, Cristina; Martinello, Katiuscia; Fucile, Sergio; Piccari, Vanessa; Mascia, Addolorata; Di Gennaro, Giancarlo; Quarato, Pier Paolo; Manfredi, Mario; Esposito, Vincenzo; Cantore, Gianpaolo; Arcella, Antonella; Simonato, Michele; Fredholm, Bertil B.; Limatola, Cristina; Miledi, Ricardo; Eusebi, Fabrizio

    2008-01-01

    We examined how the endogenous anticonvulsant adenosine might influence γ-aminobutyric acid type A (GABAA) receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 μM), GABAA receptors, microtransplanted into Xenopus oocytes from neurosurgically resected epileptic human nervous tissues, exhibited an obvious GABAA-current (IGABA) run-down, which was consistently and significantly reduced by treatment with the nonselective adenosine receptor antagonist CGS15943 (100 nM) or with adenosine deaminase (ADA) (1 units/ml), that inactivates adenosine. It was also found that selective antagonists of A2B (MRS1706, 10 nM) or A3 (MRS1334, 30 nM) receptors reduced IGABA run-down, whereas treatment with the specific A1 receptor antagonist DPCPX (10 nM) was ineffective. The selective A2A receptor antagonist SCH58261 (10 nM) reduced or potentiated IGABA run-down in ≈40% and ≈20% of tested oocytes, respectively. The ADA-resistant, AR agonist 2-chloroadenosine (2-CA) (10 μM) potentiated IGABA run-down but only in ≈20% of tested oocytes. CGS15943 administration again decreased IGABA run-down in patch-clamped neurons from either human or rat neocortex slices. IGABA run-down in pyramidal neurons was equivalent in A1 receptor-deficient and wt neurons but much larger in neurons from A2A receptor-deficient mice, indicating that, in mouse cortex, GABAA-receptor stability is tonically influenced by A2A but not by A1 receptors. IGABA run-down from wt mice was not affected by 2-CA, suggesting maximal ARs activity by endogenous adenosine. Our findings strongly suggest that cortical A2–A3 receptors alter the stability of GABAA receptors, which could offer therapeutic opportunities. PMID:18809912

  14. Human Fetal Brain-Derived Neural Stem/Progenitor Cells Grafted into the Adult Epileptic Brain Restrain Seizures in Rat Models of Temporal Lobe Epilepsy

    PubMed Central

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  15. Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex.

    PubMed

    Lang, Simone; Kroll, Alexander; Lipinski, Slawomira J; Wessa, Michèle; Ridder, Stephanie; Christmann, Christoph; Schad, Lothar R; Flor, Herta

    2009-02-01

    Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS- was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS- in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning. PMID:19200075

  16. Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex

    PubMed Central

    Lang, Simone; Kroll, Alexander; Lipinski, Slawomira J; Wessa, Michèle; Ridder, Stephanie; Christmann, Christoph; Schad, Lothar R; Flor, Herta

    2009-01-01

    Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS− in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning. PMID:19200075

  17. Alpha1-adrenoreceptor in human hippocampus: binding and receptor subtype mRNA expression.

    PubMed

    Szot, Patricia; White, Sylvia S; Greenup, J Lynne; Leverenz, James B; Peskind, Elaine R; Raskind, Murray A

    2005-10-01

    Alpha1-adrenoreceptors (AR), of which three subtypes exist (alpha1A-, alpha1B- and alpha1D-AR) are G-protein-coupled receptors that mediate the actions of norepinephrine and epinephrine both peripherally and centrally. In the CNS, alpha1-ARs are found in the hippocampus where animal studies have shown the ability of alpha1-AR agents to modulate long-term potentiation and memory; however, the precise distribution of alpha1-AR expression and its subtypes in the human brain is unknown making functional comparisons difficult. In the human hippocampus, 3H-prazosin (alpha1-AR antagonist) labels only the dentate gyrus (molecular, granule and polymorphic layers) and the stratum lucidum of the CA3 homogeneously. Human alpha1A-AR mRNA in the hippocampus is observed only in the dentate gyrus granule cell layer, while alpha1D-AR mRNA expression is observed only in the pyramidal cell layers of CA1, CA2 and CA3, regions where 3H-prazosin did not bind. alpha1B-AR mRNA is not expressed at detectable levels in the human hippocampus. These results confirm a difference in hippocampal alpha1-AR localization between rat and humans and further describe a difference in the localization of the alpha1A- and alpha1D-AR mRNA subtype between rats and humans. PMID:16039007

  18. Role of low- and high-frequency oscillations in the human hippocampus for encoding environmental novelty during a spatial navigation task.

    PubMed

    Park, Jinsick; Lee, Hojong; Kim, Taekyung; Park, Ga Young; Lee, Eun Mi; Baek, Seunghee; Ku, Jeonghun; Kim, In Young; Kim, Sun I; Jang, Dong Pyo; Kang, Joong Koo

    2014-11-01

    The hippocampus plays a key role in the encoding and retrieval of information related to novel environments during spatial navigation. However, the neural basis for these processes in the human hippocampus remains unknown because it is difficult to directly measure neural signals in the human hippocampus. This study investigated hippocampal neural oscillations involved in encoding novel environments during spatial navigation in a virtual environment. Seven epileptic patients with implanted intracranial hippocampal depth electrodes performed three sessions of virtual environment navigation. Each session consisted of a navigation task and a location-recall task. The navigation task consisted of eight blocks, and in each block, the participant navigated to the location of four different objects and was instructed to remember the location of the objects. After the eight blocks were completed, a location-recall task was performed for each of the four objects. Intracranial electroencephalography data were monitored during the navigation tasks. Theta (5-8 Hz) and delta (1-4 Hz) oscillations were lower in the first block (novel environment) than in the eighth block (familiar environment) of the navigation task, and significantly increased from block one to block eight. By contrast, low-gamma (31-50 Hz) oscillations were higher in the first block than in the eighth block of the navigation task, and significantly decreased from block one to block eight. Comparison of sessions with high recall performance (low error between identified and actual object location) and low recall performance revealed that high-gamma (51-100 Hz) oscillations significantly decreased from block one to block eight only in sessions with high recall performance. These findings suggest that delta, theta, and low-gamma oscillations were associated with encoding of environmental novelty and high-gamma oscillations were important for the successful encoding of environmental novelty. PMID:24910318

  19. Okadaic acid induces epileptic seizures and hyperphosphorylation of the NR2B subunit of the NMDA receptor in rat hippocampus in vivo.

    PubMed

    Arias, Clorinda; Montiel, Teresa; Peña, Fernando; Ferrera, Patricia; Tapia, Ricardo

    2002-09-01

    Overactivation of N-methyl-D-aspartate (NMDA) glutamate receptors is closely related to epilepsy and excitotoxicity, and the phosphorylation of these receptors may facilitate glutamate-mediated synaptic transmission. Here we show that in awake rats the microinjection into the hippocampus of okadaic acid, a potent inhibitor of protein phosphatases 1 and 2A, induces in about 20 min intense electroencephalographic and behavioral limbic-type seizures, which are suppressed by the systemic administration of the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine hydrogen maleate and by the intrahippocampal administration of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, an inhibitor of protein kinases. Two hours after okadaic acid, when the EEG seizures were intense, an increased serine phosphorylation of some hippocampal proteins, including an enhancement of the serine phosphorylation of the NMDA receptor subunit NR2B, was detected by immunoblotting. Twenty-four hours after okadaic acid a marked destruction of hippocampal CA1 region was observed, which was not prevented by the receptor antagonists. These findings suggest that hyperphosphorylation of glutamate receptors in vivo may result in an increased sensitivity to the endogenous transmitter and therefore induce neuronal hyperexcitability and epilepsy. PMID:12429230

  20. Impaired Action Potential Initiation in GABAergic Interneurons Causes Hyperexcitable Networks in an Epileptic Mouse Model Carrying a Human NaV1.1 Mutation

    PubMed Central

    Hedrich, Ulrike B.S.; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz

    2014-01-01

    Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na+ channels in interneurons and persistent Na+ currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca2+ imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. PMID:25378155

  1. Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

    ERIC Educational Resources Information Center

    Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

    2015-01-01

    Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

  2. Double Dissociation of Conditioning and Declarative Knowledge Relative to the Amygdala and Hippocampus in Humans

    NASA Astrophysics Data System (ADS)

    Bechara, Antoine; Tranel, Daniel; Damasio, Hanna; Adolphs, Ralph; Rockland, Charles; Damasio, Antonio R.

    1995-08-01

    A patient with selective bilateral damage to the amygdala did not acquire conditioned autonomic responses to visual or auditory stimuli but did acquire the declarative facts about which visual or auditory stimuli were paired with the unconditioned stimulus. By contrast, a patient with selective bilateral damage to the hippocampus failed to acquire the facts but did acquire the conditioning. Finally, a patient with bilateral damage to both amygdala and hippocampal formation acquired neither the conditioning nor the facts. These findings demonstrate a double dissociation of conditioning and declarative knowledge relative to the human amygdala and hippocampus.

  3. Physical Exercise Habits Correlate with Gray Matter Volume of the Hippocampus in Healthy Adult Humans

    NASA Astrophysics Data System (ADS)

    Killgore, William D. S.; Olson, Elizabeth A.; Weber, Mareen

    2013-12-01

    Physical activity facilitates neurogenesis of dentate cells in the rodent hippocampus, a brain region critical for memory formation and spatial representation. Recent findings in humans also suggest that aerobic exercise can lead to increased hippocampal volume and enhanced cognitive functioning in children and elderly adults. However, the association between physical activity and hippocampal volume during the period from early adulthood through middle age has not been effectively explored. Here, we correlated the number of minutes of self-reported exercise per week with gray matter volume of the hippocampus using voxel-based morphometry (VBM) in 61 healthy adults ranging from 18 to 45 years of age. After controlling for age, gender, and total brain volume, total minutes of weekly exercise correlated significantly with volume of the right hippocampus. Findings highlight the relationship between regular physical exercise and brain structure during early to middle adulthood.

  4. Julius Caesar Arantius (Giulio Cesare Aranzi, 1530-1589) and the hippocampus of the human brain: history behind the discovery.

    PubMed

    Bir, Shyamal C; Ambekar, Sudheer; Kukreja, Sunil; Nanda, Anil

    2015-04-01

    Julius Caesar Arantius is one of the pioneer anatomists and surgeons of the 16th century who discovered the different anatomical structures of the human body. One of his prominent discoveries is the hippocampus. At that time, Arantius originated the term hippocampus, from the Greek word for seahorse (hippos ["horse"] and kampos ["sea monster"]). Arantius published his description of the hippocampus in 1587, in the first chapter of his work titled De Humano Foetu Liber. Numerous nomenclatures of this structure, including "white silkworm," "Ammon's horn," and "ram's horn" were proposed by different scholars at that time. However, the term hippocampus has become the most widely used in the literature. PMID:25574573

  5. Gene Expression in Human Hippocampus from Cocaine Abusers Identifies Genes which Regulate Extracellular Matrix Remodeling

    PubMed Central

    Mash, Deborah C.; ffrench-Mullen, Jarlath; Adi, Nikhil; Qin, Yujing; Buck, Andrew; Pablo, John

    2007-01-01

    The chronic effects of cocaine abuse on brain structure and function are blamed for the inability of most addicts to remain abstinent. Part of the difficulty in preventing relapse is the persisting memory of the intense euphoria or cocaine “rush”. Most abused drugs and alcohol induce neuroplastic changes in brain pathways subserving emotion and cognition. Such changes may account for the consolidation and structural reconfiguration of synaptic connections with exposure to cocaine. Adaptive hippocampal plasticity could be related to specific patterns of gene expression with chronic cocaine abuse. Here, we compare gene expression profiles in the human hippocampus from cocaine addicts and age-matched drug-free control subjects. Cocaine abusers had 151 gene transcripts upregulated, while 91 gene transcripts were downregulated. Topping the list of cocaine-regulated transcripts was RECK in the human hippocampus (FC = 2.0; p<0.05). RECK is a membrane-anchored MMP inhibitor that is implicated in the coordinated regulation of extracellular matrix integrity and angiogenesis. In keeping with elevated RECK expression, active MMP9 protein levels were decreased in the hippocampus from cocaine abusers. Pathway analysis identified other genes regulated by cocaine that code for proteins involved in the remodeling of the cytomatrix and synaptic connections and the inhibition of blood vessel proliferation (PCDH8, LAMB1, ITGB6, CTGF and EphB4). The observed microarray phenotype in the human hippocampus identified RECK and other region-specific genes that may promote long-lasting structural changes with repeated cocaine abuse. Extracellular matrix remodeling in the hippocampus may be a persisting effect of chronic abuse that contributes to the compulsive and relapsing nature of cocaine addiction. PMID:18000554

  6. Defining the human hippocampus in cerebral magnetic resonance images—An overview of current segmentation protocols

    PubMed Central

    Konrad, C.; Ukas, T.; Nebel, C.; Arolt, V.; Toga, A.W.; Narr, K.L.

    2011-01-01

    Due to its crucial role for memory processes and its relevance in neurological and psychiatric disorders, the hippocampus has been the focus of neuroimaging research for several decades. In vivo measurement of human hippocampal volume and shape with magnetic resonance imaging has become an important element of neuroimaging research. Nevertheless, volumetric findings are still inconsistent and controversial for many psychiatric conditions including affective disorders. Here we review the wealth of anatomical protocols for the delineation of the hippocampus in MR images, taking into consideration 71 different published protocols from the neuroimaging literature, with an emphasis on studies of affective disorders. We identified large variations between protocols in five major areas. 1) The inclusion/exclusion of hippocampal white matter (alveus and fimbria), 2) the definition of the anterior hippocampal–amygdala border, 3) the definition of the posterior border and the extent to which the hippocampal tail is included, 4) the definition of the inferior medial border of the hippocampus, and 5) the use of varying arbitrary lines. These are major sources of variance between different protocols. In contrast, the definitions of the lateral, superior, and inferior borders are less disputed. Directing resources to replication studies that incorporate characteristics of the segmentation protocols presented herein may help resolve seemingly contradictory volumetric results between prior neuroimaging studies and facilitate the appropriate selection of protocols for manual or automated delineation of the hippocampus for future research purposes. PMID:19447182

  7. Human hippocampus represents space and time during retrieval of real-world memories

    PubMed Central

    Nielson, Dylan M.; Smith, Troy A.; Sreekumar, Vishnu; Dennis, Simon; Sederberg, Per B.

    2015-01-01

    Memory stretches over a lifetime. In controlled laboratory settings, the hippocampus and other medial temporal lobe brain structures have been shown to represent space and time on the scale of meters and seconds. It remains unclear whether the hippocampus also represents space and time over the longer scales necessary for human episodic memory. We recorded neural activity while participants relived their own experiences, cued by photographs taken with a custom lifelogging device. We found that the left anterior hippocampus represents space and time for a month of remembered events occurring over distances of up to 30 km. Although previous studies have identified similar drifts in representational similarity across space or time over the relatively brief time scales (seconds to minutes) that characterize individual episodic memories, our results provide compelling evidence that a similar pattern of spatiotemporal organization also exists for organizing distinct memories that are distant in space and time. These results further support the emerging view that the anterior, as opposed to posterior, hippocampus integrates distinct experiences, thereby providing a scaffold for encoding and retrieval of autobiographical memories on the scale of our lives. PMID:26283350

  8. Phosphatase inhibitors remove the run-down of γ-aminobutyric acid type A receptors in the human epileptic brain

    PubMed Central

    Palma, E.; Ragozzino, D. A.; Di Angelantonio, S.; Spinelli, G.; Trettel, F.; Martinez-Torres, A.; Torchia, G.; Arcella, A.; Di Gennaro, G.; Quarato, P. P.; Esposito, V.; Cantore, G.; Miledi, R.; Eusebi, F.

    2004-01-01

    The properties of γ-aminobutyric acid (GABA) type A receptors (GABAA receptors) microtransplanted from the human epileptic brain to the plasma membrane of Xenopus oocytes were compared with those recorded directly from neurons, or glial cells, in human brains slices. Cell membranes isolated from brain specimens, surgically obtained from six patients afflicted with drug-resistant temporal lobe epilepsy (TLE) were injected into frog oocytes. Within a few hours, these oocytes acquired GABAA receptors that generated GABA currents with an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, receptors derived from membranes of a nonepileptic hippocampal uncus, membranes from mouse brain, or recombinant rat α1β2γ2-GABA receptors exhibited a much less pronounced GABA-current run-down. Moreover, the GABAA receptors of pyramidal neurons in temporal neocortex slices from the same six epileptic patients exhibited a stronger run-down than the receptors of rat pyramidal neurons. Interestingly, the GABAA receptors of neighboring glial cells remained substantially stable after repetitive activation. Therefore, the excessive GABA-current run-down observed in the membrane-injected oocytes recapitulates essentially what occurs in neurons, rather than in glial cells. Quantitative RT-PCR analyses from the same TLE neocortex specimens revealed that GABAA-receptor β1, β2, β3, and γ2 subunit mRNAs were significantly overexpressed (8- to 33-fold) compared with control autopsy tissues. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE brain leads to the expression of run-down-enhanced GABAA receptors. Blockage of phosphatases stabilizes the TLE GABAA receptors and strengthens GABAergic inhibition. It may be that this process can be targeted to develop new treatments for intractable epilepsy. PMID:15218107

  9. Detecting directional coupling in the human epileptic brain: Limitations and potential pitfalls

    NASA Astrophysics Data System (ADS)

    Osterhage, Hannes; Mormann, Florian; Wagner, Tobias; Lehnertz, Klaus

    2008-01-01

    We study directional relationships—in the driver-responder sense—in networks of coupled nonlinear oscillators using a phase modeling approach. Specifically, we focus on the identification of drivers in clusters with varying levels of synchrony, mimicking dynamical interactions between the seizure generating region (epileptic focus) and other brain structures. We demonstrate numerically that such an identification is not always possible in a reliable manner. Using the same analysis techniques as in model systems, we study multichannel electroencephalographic recordings from two patients suffering from focal epilepsy. Our findings demonstrate that—depending on the degree of intracluster synchrony—certain subsystems can spuriously appear to be driving others, which should be taken into account when analyzing field data with unknown underlying dynamics.

  10. Atypical pyramidal cells in epileptic human cortex: CFLS and 3-D reconstructions.

    PubMed

    Belichencko, P; Dahlström, A; von Essen, C; Lindström, S; Nordborg, C; Sourander, P

    1992-09-01

    Epileptic temporal cortices, removed from 3 patients with intractable partial epilepsy (IPE) during neurosurgery, were studied. Pyramidal neurons (40-50 per slice) in laminae III, V and white matter, were injected with lucifer yellow. Samples were examined in a confocal laser scanning microscope (Biorad 600) and individual cells scanned at 0.1-1 microns incremental levels. 2-D maximal linear projection was used for overview. Frames (50-60) of scanned neurons were transformed into 3-D volumes, using VoxelView software on a Silicone Graphics workstation and rotated. All samples contained neurons with duplicated apical dendrites, additional basal dendrites or were misplaced in a horizontal position in the white matter. The relation between these preliminary observations and the disease is discussed. PMID:1421134

  11. Antidepressants increase neural progenitor cells in the human hippocampus

    PubMed Central

    Boldrini, Maura; Underwood, Mark D.; Hen, René; Rosoklija, Gorazd B.; Dwork, Andrew J.; Mann, J. John; Arango, Victoria

    2009-01-01

    Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) increase neurogenesis in the dentate gyrus (DG) of rodents and nonhuman primates. We determined whether SSRIs or TCAs increase neural progenitor (NPCs) and dividing cells in the human DG in major depressive disorder (MDD). Whole frozen hippocampi from untreated subjects with MDD (N = 5), antidepressant-treated MDD (MDDT, N = 7), and controls (C, N = 7) were fixed, sectioned and immunostained for NPCs and dividing cell markers (nestin and Ki-67 respectively), NeuN and GFAP, in single and double labeling. NPC and dividing cell numbers in the DG were estimated by stereology. Clinical data were obtained by psychological autopsy and toxicological and neuropathological examination performed in all subjects. NPCs decreased with age (p = 0.034). Females had more NPCs than males (p = 0.023). Correcting for age and sex, MDDT receiving SSRIs had more NPCs than untreated MDD (p ≤ 0.001) and controls (p ≤ 0.001), NPCs were not different in SSRIs- and TCAs-treated MDDT (p = 0.169). Dividing cell number, unaffected by age or sex, was greater in MDDT receiving TCAs than in untreated MDD (p ≤ 0.001), SSRI-treated MDD (p = 0.001) and controls (p ≤ 0.001). The NPCs and dividing cells increase in MDDT was localized to the rostral DG. MDDT had a larger DG volume compared with untreated MDD or controls (p = 0.009). Antidepressants increase neural progenitor cell number in the anterior human dentate gyrus. Whether this finding is critical or necessary for the antidepressants effect remains to be determined. PMID:19606083

  12. Synchronization of stochastic systems: from paddlefish electroreceptors to human epileptic glial cell cultures

    NASA Astrophysics Data System (ADS)

    Neiman, Alexander

    2000-03-01

    Synchronization is one of the fundamental nonlinear phenomena observed in nature. We have studied stochastic synchronization in the electrosensitive system of the paddlefish, Polyodon spathula and have also applied synchronization analysis to networks of glial cells cultured from brain tissue of patients with severe epilepsy. We also present theoretical and numerical models for stochastic synchronization. The electrosensitive system of the paddlefish consists of tens of thousands of electroreceptors located mainly on the "rostrum", which serves as an antenna to locate plankton. Each electroreceptor is a noisy oscillator with natural frequencies in the range of 30-90 Hz. We study synchronization in vivo due to 3-20 Hz external periodic electric fields, which correspond to natural signals produced by Daphnia, the usual prey of paddlefish. We find that for signals whose strengths are in the range that paddlefish customarily encounter in the wild, synchronization coding offers a plausible alternative to the more usual rate coding. We also have studied mutual synchronization between different electroreceptors. Although the spontaneous firing of distant electroreceptors is not synchronized, synchronization is observed when external periodic or even noisy electric fields are applied. We have applied the same analysis techniques to examine synchronization between groups of glial cells. In contrast to cultures of healthy astrocytes, which demonstrate calcium waves, the networks from epileptic tissue are characterized by spatially disordered hyper activity. Nevertheless, we have found that, in many cases, synchronized activity is a rather typical for tissue taken from the uncus region of the brain.

  13. Phenytoin influence on human lymphocyte mitogen response: a prospective study of epileptic and nonepileptic patients.

    PubMed

    Gabourel, J D; Davies, G H; Bardana, E J; Ratzlaff, N A

    1982-08-01

    The results of this prospective study fail to confirm previously reported phenytoin suppression of lymphocyte responsiveness to mitogens. Our data show a significantly greater than expected percentage (p less than 0.0001) of patients requiring phenytoin treatment have low lymphocyte responsiveness to mitogens prior to phenytoin therapy. Analysis of changes in each individual's response during phenytoin treatment as compared with their pre-phenytoin responses shows a consistent trend to increased responsiveness to concanavalin A, pokeweed mitogen, and to a suboptimal concentration of phytohemagglutinin. This trend was most pronounced for patients whose serum IgA concentration was decreased while taking phenytoin, whereas there was no such trend for individuals whose serum IgA levels were not decreased. This phenomenon was not related to neurological disease classification. Phenytoin added directly to lymphocyte cultures depressed lymphocyte responses to all mitogens in a small (less than 20%) but significant degree, confirming similar in vitro studies by other investigators. Because of limited serum proteins for phenytoin binding in culture medium, these in vitro studies have little application to possible phenytoin effects on lymphocytes of patients taking it to prevent seizures. Thus, the suggestion that phenytoin causes depressed lymphocyte responses to mitogens in epileptic patients appears unwarranted. PMID:7094904

  14. The human hippocampus is not sexually-dimorphic: Meta-analysis of structural MRI volumes.

    PubMed

    Tan, Anh; Ma, Wenli; Vira, Amit; Marwha, Dhruv; Eliot, Lise

    2016-01-01

    Hippocampal atrophy is found in many psychiatric disorders that are more prevalent in women. Sex differences in memory and spatial skills further suggest that males and females differ in hippocampal structure and function. We conducted the first meta-analysis of male-female difference in hippocampal volume (HCV) based on published MRI studies of healthy participants of all ages, to test whether the structure is reliably sexually dimorphic. Using four search strategies, we collected 68 matched samples of males' and females' uncorrected HCVs (in 4418 total participants), and 36 samples of male and female HCVs (2183 participants) that were corrected for individual differences in total brain volume (TBV) or intracranial volume (ICV). Pooled effect sizes were calculated using a random-effects model for left, right, and bilateral uncorrected HCVs and for left and right HCVs corrected for TBV or ICV. We found that uncorrected HCV was reliably larger in males, with Hedges' g values of 0.545 for left hippocampus, 0.526 for right hippocampus, and 0.557 for bilateral hippocampus. Meta-regression revealed no effect of age on the sex difference in left, right, or bilateral HCV. In the subset of studies that reported it, both TBV (g=1.085) and ICV (g=1.272) were considerably larger in males. Accordingly, studies reporting HCVs corrected for individual differences in TBV or ICV revealed no significant sex differences in left and right HCVs (Hedges' g ranging from +0.011 to -0.206). In summary, we found that human males of all ages exhibit a larger HCV than females, but adjusting for individual differences in TBV or ICV results in no reliable sex difference. The frequent claim that women have a disproportionately larger hippocampus than men was not supported. PMID:26334947

  15. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

    PubMed Central

    Barman, Adriana; Assmann, Anne; Richter, Sylvia; Soch, Joram; Schütze, Hartmut; Wüstenberg, Torsten; Deibele, Anna; Klein, Marieke; Richter, Anni; Behnisch, Gusalija; Düzel, Emrah; Zenker, Martin; Seidenbecher, Constanze I.; Schott, Björn H.

    2014-01-01

    The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP) rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT) and the logical memory section of the Wechsler Memory Scale (WMS). Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI) studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e., the myopia risk allele) showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point toward pleitropic effects of RASGRF1 genetic variations on complex neural function in humans. PMID:24808846

  16. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory.

    PubMed

    Barman, Adriana; Assmann, Anne; Richter, Sylvia; Soch, Joram; Schütze, Hartmut; Wüstenberg, Torsten; Deibele, Anna; Klein, Marieke; Richter, Anni; Behnisch, Gusalija; Düzel, Emrah; Zenker, Martin; Seidenbecher, Constanze I; Schott, Björn H

    2014-01-01

    The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP) rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT) and the logical memory section of the Wechsler Memory Scale (WMS). Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI) studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e., the myopia risk allele) showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point toward pleitropic effects of RASGRF1 genetic variations on complex neural function in humans. PMID:24808846

  17. Pattern of P450 expression at the human blood–brain barrier: Roles of epileptic condition and laminar flow

    PubMed Central

    Ghosh, Chaitali; Gonzalez-Martinez, Jorge; Hossain, Mohammed; Cucullo, Luca; Fazio, Vincent; Janigro, Damir; Marchi, Nicola

    2011-01-01

    Summary Purpose P450 enzymes (CYPs) play a major role in hepatic drug metabolism. It is unclear whether these enzymes are functionally expressed by the diseased human blood–brain barrier (BBB) and are involved in local drug metabolism or response. We have evaluated the cerebrovascular CYP expression and function, hypothesizing possible implication in drug-resistant epilepsy. Methods CYP P450 transcript levels were assessed by cDNA microarray in primary endothelial cultures established from a cohort of brain resections (n = 12, drug-resistant epilepsy EPI-EC and aneurism domes ANE-EC). A human brain endothelial cell line (HBMEC) and non-brain endothelial cell line (HUVEC) were used as controls. The effect of exposure to shear stress on CYP expression was evaluated. Results were confirmed by Western blot and immunohistochemistry on brain specimens. Endothelial drug metabolism was assessed by high performance liquid chromatography (HPLC-UV). Results cDNA microarray showed the presence of CYP enzymes in isolated human primary brain endothelial cells. Using EPI-EC and HBMEC we found that CYP mRNA levels were significantly affected by exposure to shear stress. CYP3A4 protein was overexpressed in EPI-EC (290 ± 30%) compared to HBMEC and further upregulated by shear stress exposure. CYP3A4 was increased in the vascular compartment at regions of reactive gliosis in the drug-resistant epileptic brain. Metabolism of carbamazepine was significantly elevated in EPI-EC compared to HBMEC. Discussion These results support the hypothesis of local drug metabolism at the diseased BBB. The direct association between BBB CYP enzymes and the drug-resistant phenotype needs to be further investigated. PMID:20074231

  18. Species-specific ultrastructure of neuronal lipofuscin in hippocampus and neocortex of subhuman mammals and humans.

    PubMed

    Boellaard, J W; Schlote, W; Hofer, W

    2004-01-01

    Lipofuscin represents an integral part of neurons and glial cells in mammals and in submammalian species. It is a special lysosomal organelle, takes part of cellular metabolism, and is a structural expression of catabolic pathways. Species-specific differences of lipofuscin indicate metabolic differences of the relevant neurons. The authors have studied the ultrastructure of neuronal lipofuscin in the hippocampus and cerebral neocortex of dogs, horses, cows, elephants, rats, mice, apes, and humans to answer the question of species-specific differences of this organelle. Paraffin sections of formalin-fixed material were investigated by hematoxylin-eosin and PAS staining, by fluorescence microscopy for autofluorescence, with a laser scanning confocal microscope and by electron microscopy. In the animals studied and in humans the lipofuscin displayed, in addition to the general trilaminar substructure, species-specific appearances. No differences were found in the lipofuscin structure between neocortical and hippocampal neurons of the separate animal species. In contrast, in humans, neurons of the hippocampus showed a particular lipofuscin structure, not only different from the neocortical one, but also with differences between CA1 and CA3/4 sectors. Interestingly, in apes a transitional situation was found with slight differences between neocortical and hippocampal lipofuscin, especially in the rhesus monkey. This peculiarity was corroborated by the distribution of special pentilaminar linear structures in the lipofuscin pigment in all animals, only sparsely in the rhesus monkey and not in humans. The results indicate that lipofuscin ultrastructure of neocortical and hippocampal neurons is species specific and that lipofuscin in the human hippocampal neurons displays structures characteristic of man differing from the neocortical neuronal lipofuscin. The neuronal lipofuscin of apes, especially of the rhesus monkey displays structures in between humans and lower

  19. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus.

    PubMed

    Suderman, Matthew; McGowan, Patrick O; Sasaki, Aya; Huang, Tony C T; Hallett, Michael T; Meaney, Michael J; Turecki, Gustavo; Szyf, Moshe

    2012-10-16

    Early life experience is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, it is unlikely that such effects completely capture the evolutionarily conserved epigenetic mechanisms of early adaptation to environment. Here we present DNA methylation profiles spanning 6.5 million base pairs centered at the NR3C1 gene in the hippocampus of humans who experienced abuse as children and nonabused controls. We compare these profiles to corresponding DNA methylation profiles in rats that received differential levels of maternal care. The profiles of both species reveal hundreds of DNA methylation differences associated with early life experience distributed across the entire region in nonrandom patterns. For instance, methylation differences tend to cluster by genomic location, forming clusters covering as many as 1 million bases. Even more surprisingly, these differences seem to specifically target regulatory regions such as gene promoters, particularly those of the protocadherin α, β, and γ gene families. Beyond these high-level similarities, more detailed analyses reveal methylation differences likely stemming from the significant biological and environmental differences between species. These results provide support for an analogous cross-species epigenetic regulatory response at the level of the genomic region to early life experience. PMID:23045659

  20. Decoding illusory self-location from activity in the human hippocampus

    PubMed Central

    Guterstam, Arvid; Björnsdotter, Malin; Bergouignan, Loretxu; Gentile, Giovanni; Li, Tie-Qiang; Ehrsson, H. Henrik

    2015-01-01

    Decades of research have demonstrated a role for the hippocampus in spatial navigation and episodic and spatial memory. However, empirical evidence linking hippocampal activity to the perceptual experience of being physically located at a particular place in the environment is lacking. In this study, we used a multisensory out-of-body illusion to perceptually ‘teleport’ six healthy participants between two different locations in the scanner room during high-resolution functional magnetic resonance imaging (fMRI). The participants were fitted with MRI-compatible head-mounted displays that changed their first-person visual perspective to that of a pair of cameras placed in one of two corners of the scanner room. To elicit the illusion of being physically located in this position, we delivered synchronous visuo-tactile stimulation in the form of an object moving toward the cameras coupled with touches applied to the participant’s chest. Asynchronous visuo-tactile stimulation did not induce the illusion and served as a control condition. We found that illusory self-location could be successfully decoded from patterns of activity in the hippocampus in all of the participants in the synchronous (P < 0.05) but not in the asynchronous condition (P > 0.05). At the group-level, the decoding accuracy was significantly higher in the synchronous than in the asynchronous condition (P = 0.012). These findings associate hippocampal activity with the perceived location of the bodily self in space, which suggests that the human hippocampus is involved not only in spatial navigation and memory but also in the construction of our sense of bodily self-location. PMID:26236222

  1. Decoding illusory self-location from activity in the human hippocampus.

    PubMed

    Guterstam, Arvid; Björnsdotter, Malin; Bergouignan, Loretxu; Gentile, Giovanni; Li, Tie-Qiang; Ehrsson, H Henrik

    2015-01-01

    Decades of research have demonstrated a role for the hippocampus in spatial navigation and episodic and spatial memory. However, empirical evidence linking hippocampal activity to the perceptual experience of being physically located at a particular place in the environment is lacking. In this study, we used a multisensory out-of-body illusion to perceptually 'teleport' six healthy participants between two different locations in the scanner room during high-resolution functional magnetic resonance imaging (fMRI). The participants were fitted with MRI-compatible head-mounted displays that changed their first-person visual perspective to that of a pair of cameras placed in one of two corners of the scanner room. To elicit the illusion of being physically located in this position, we delivered synchronous visuo-tactile stimulation in the form of an object moving toward the cameras coupled with touches applied to the participant's chest. Asynchronous visuo-tactile stimulation did not induce the illusion and served as a control condition. We found that illusory self-location could be successfully decoded from patterns of activity in the hippocampus in all of the participants in the synchronous (P < 0.05) but not in the asynchronous condition (P > 0.05). At the group-level, the decoding accuracy was significantly higher in the synchronous than in the asynchronous condition (P = 0.012). These findings associate hippocampal activity with the perceived location of the bodily self in space, which suggests that the human hippocampus is involved not only in spatial navigation and memory but also in the construction of our sense of bodily self-location. PMID:26236222

  2. MicroRNA profiles in hippocampal granule cells and plasma of rats with pilocarpine-induced epilepsy – comparison with human epileptic samples

    PubMed Central

    Roncon, Paolo; Soukupovà, Marie; Binaschi, Anna; Falcicchia, Chiara; Zucchini, Silvia; Ferracin, Manuela; Langley, Sarah R.; Petretto, Enrico; Johnson, Michael R.; Marucci, Gianluca; Michelucci, Roberto; Rubboli, Guido; Simonato, Michele

    2015-01-01

    The identification of biomarkers of the transformation of normal to epileptic tissue would help to stratify patients at risk of epilepsy following brain injury, and inform new treatment strategies. MicroRNAs (miRNAs) are an attractive option in this direction. In this study, miRNA microarrays were performed on laser-microdissected hippocampal granule cell layer (GCL) and on plasma, at different time points in the development of pilocarpine-induced epilepsy in the rat: latency, first spontaneous seizure and chronic epileptic phase. Sixty-three miRNAs were differentially expressed in the GCL when considering all time points. Three main clusters were identified that separated the control and chronic phase groups from the latency group and from the first spontaneous seizure group. MiRNAs from rats in the chronic phase were compared to those obtained from the laser-microdissected GCL of epileptic patients, identifying several miRNAs (miR-21-5p, miR-23a-5p, miR-146a-5p and miR-181c-5p) that were up-regulated in both human and rat epileptic tissue. Analysis of plasma samples revealed different levels between control and pilocarpine-treated animals for 27 miRNAs. Two main clusters were identified that segregated controls from all other groups. Those miRNAs that are altered in plasma before the first spontaneous seizure, like miR-9a-3p, may be proposed as putative biomarkers of epileptogenesis. PMID:26382856

  3. MicroRNA profiles in hippocampal granule cells and plasma of rats with pilocarpine-induced epilepsy--comparison with human epileptic samples.

    PubMed

    Roncon, Paolo; Soukupovà, Marie; Binaschi, Anna; Falcicchia, Chiara; Zucchini, Silvia; Ferracin, Manuela; Langley, Sarah R; Petretto, Enrico; Johnson, Michael R; Marucci, Gianluca; Michelucci, Roberto; Rubboli, Guido; Simonato, Michele

    2015-01-01

    The identification of biomarkers of the transformation of normal to epileptic tissue would help to stratify patients at risk of epilepsy following brain injury, and inform new treatment strategies. MicroRNAs (miRNAs) are an attractive option in this direction. In this study, miRNA microarrays were performed on laser-microdissected hippocampal granule cell layer (GCL) and on plasma, at different time points in the development of pilocarpine-induced epilepsy in the rat: latency, first spontaneous seizure and chronic epileptic phase. Sixty-three miRNAs were differentially expressed in the GCL when considering all time points. Three main clusters were identified that separated the control and chronic phase groups from the latency group and from the first spontaneous seizure group. MiRNAs from rats in the chronic phase were compared to those obtained from the laser-microdissected GCL of epileptic patients, identifying several miRNAs (miR-21-5p, miR-23a-5p, miR-146a-5p and miR-181c-5p) that were up-regulated in both human and rat epileptic tissue. Analysis of plasma samples revealed different levels between control and pilocarpine-treated animals for 27 miRNAs. Two main clusters were identified that segregated controls from all other groups. Those miRNAs that are altered in plasma before the first spontaneous seizure, like miR-9a-3p, may be proposed as putative biomarkers of epileptogenesis. PMID:26382856

  4. Hierarchical nesting of slow oscillations, spindles and ripples in the human hippocampus during sleep

    PubMed Central

    Bonnefond, Mathilde; van der Meij, Roemer; Jensen, Ole; Deuker, Lorena; Elger, Christian E.; Axmacher, Nikolai; Fell, Juergen

    2015-01-01

    During systems-level consolidation, mnemonic representations initially reliant on the hippocampus are thought to migrate to neocortical sites for more permanent storage, with an eminent role of sleep for facilitating this information transfer. Mechanistically, consolidation processes have been hypothesized to rely on systematic interactions between the three cardinal neuronal oscillations characterizing non-rapid-eye-movement sleep: Under global control of de- and hyperpolarizing slow oscillations (SOs), sleep spindles may cluster hippocampal ripples for a precisely timed transfer of local information to the neocortex. Here we used direct intracranial electroencephalogram (iEEG) recordings from human epilepsy patients during natural sleep to test the assumption that SOs, spindles and ripples are functionally coupled in the hippocampus. Employing cross-frequency phase-amplitude coupling analyses, we first show that spindles are modulated by the up-state of SOs. Critically, spindles were found to in turn cluster ripples in their troughs, providing fine-tuned temporal frames for the hypothesized transfer of hippocampal memory traces. PMID:26389842

  5. Property of Regenerating Serotonin Fibers in the Hippocampus of Human Migration Disorders Model

    NASA Astrophysics Data System (ADS)

    Ueda, Shuichi; Ehara, Ayuka; Ohmomo, Hideki

    Individual mood and mental conditions exert a great influence on one's own kansei. Abnormality or dysfunction of the 5-HT neuron system in the developing and/or adult brain is closely associated with their conditions. Thus, the 5-HT neuron system may play an important role in the neuronal mechanisms underlying kansei. Interestingly, previous studies have shown that heterotopic clusters in the hippocampus (hippocampal heterotopia), deriving from neocortical neurons, after prenatally treated with methylazoxymethanol acetate in rat (MAM rat), exhibit abundant 5-HT innervation. After neonatal intracisternal 5, 7-dihydroxytryptamine (DHT) injection, these 5-HT fibers degenerate and disappear throughout the forebrain, and then regenerating 5-HT fibers densely innervate in the hippocampal heterotopia. The 5-HT fiber system in the hippocampal heterotopia of MAM rat provides useful experimental models for study the plasticity of human migration disorder. In the present study, to evaluate the properties of regenerating 5-HT fibers in the hippocampal heterotopia of MAM rats, we examined the origin of these projections by combined retrograde transport and immunohistochemical methods. Prenatal exposure to MAM resulted in the formation of hippocampal heterotopia in the dorsal hippocampus. Regenerating 5-HT fibers formed a dense innervation within the hippocampal heterotopia after neonatal DHT injection. These projections appeared to arise mainly from 5-HT neurons in the median raphe nucleus, with a small portion from 5-HT neurons in the dorsal raphe nucleus. These findings suggest a specific profile of regenerating 5-HT fibers, providing the new insights for serotonergic plasticity.

  6. Electroencephalographic features of familial spontaneous epileptic cats.

    PubMed

    Hasegawa, Daisuke; Mizoguchi, Shunta; Kuwabara, Takayuki; Hamamoto, Yuji; Ogawa, Fukie; Matsuki, Naoaki; Uchida, Kazuyuki; Fujita, Michio

    2014-08-01

    A feline strain of familial spontaneous epileptic cats (FSECs) with typical limbic seizures was identified in 2010, and have been maintained as a novel animal model of genetic epilepsy. In this study, we characterized the electroencephalographic (EEG) features of FSECs. On scalp EEG under sedation, FSECs showed sporadic, but comparatively frequent interictal discharges dominantly in the uni- or bilateral temporal region. Bemegride activation was performed in order to evaluate the predisposition of epileptogenicity of FSECs. The threshold doses of the first paroxysmal discharge, clinical myoclonus and generalized convulsion in FSECs were significantly lower than those in control cats. Chronic video-intracranial EEG monitoring revealed subclinical or clinical focal seizures with secondarily generalization onset from the unilateral amygdala and/or hippocampus. Clinical generalized seizures were also recorded, but we were unable to detect the onset site. The results of the present study show that FSECs resemble not only feline kindling or the kainic acid model and El mouse, but also human familial or sporadic mesial temporal lobe epilepsy. In addition, our results indicate that FSECs are a natural and valuable model of mesial temporal lobe epilepsy. PMID:24893833

  7. Internally Generated Reactivation of Single Neurons in Human Hippocampus During Free Recall

    PubMed Central

    Gelbard-Sagiv, Hagar; Mukamel, Roy; Harel, Michal; Malach, Rafael; Fried, Itzhak

    2009-01-01

    The emergence of memory, a trace of things past, into human consciousness is one of the greatest mysteries of the human mind. Whereas the neuronal basis of recognition memory can be probed experimentally in human and nonhuman primates, the study of free recall requires that the mind declare the occurrence of a recalled memory (an event intrinsic to the organism and invisible to an observer). Here, we report the activity of single neurons in the human hippocampus and surrounding areas when subjects first view cinematic episodes consisting of audiovisual sequences and again later when they freely recall these episodes. A subset of these neurons exhibited selective firing, which often persisted throughout and following specific episodes for as long as 12 seconds. Verbal reports of memories of these specific episodes at the time of free recall were preceded by selective reactivation of the same hippocampal and entorhinal cortex neurons. We suggest that this reactivation is an internally generated neuronal correlate for the subjective experience of spontaneous emergence of human recollection. PMID:18772395

  8. Adult-onset focal expression of mutated human tau in the hippocampus impairs spatial working memory of rats

    PubMed Central

    Mustroph, M.L.; King, M.A.; Klein, R.L.; Ramirez, J.J.

    2012-01-01

    Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer’s disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adult-onset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks post-transduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains for expression of human tau revealed hyperphosphorylated human tau and NFTs in the hippocampus in experimental animals only. Thus, adult-onset, vector-induced tauopathy spatially restricted to the hippocampus progressively impaired spatial working memory in rats. We conclude that the model faithfully reproduces histological and behavioral findings characteristic of dementing tauopathies. The rapid onset of sustained memory impairment establishes a preclinical model particularly suited to the development of potential tauopathy therapeutics. PMID:22561128

  9. Glycosaminoglycans from aged human hippocampus have altered capacities to regulate trophic factors activities but not Aβ42 peptide toxicity.

    PubMed

    Huynh, Minh Bao; Villares, Joao; Díaz, Julia Elisa Sepúlveda; Christiaans, Stephy; Carpentier, Gilles; Ouidja, Mohand Ouidir; Sissoeff, Ludmilla; Raisman-Vozari, Rita; Papy-Garcia, Dulce

    2012-05-01

    Glycosaminoglycans (GAGs) are major extracellular matrix components known to tightly regulate cell behavior by interacting with tissue effectors as trophic factors and other heparin binding proteins. Alterations of GAGs structures might thus modify the nature and extent of these interactions and alter tissue integrity. Here, we studied levels and composition of GAGs isolated from adult and aged human hippocampus and investigated if their changes can influence the function of important trophic factors and the Aβ42 peptide toxicity. Biochemical analyses showed that heparan sulfates are increased in the aged hippocampus. Moreover, GAGs from aged hippocampus showed altered capacities to regulate trophic factor activities without changing their capacities to protect cells from Aβ42 toxicity, compared to adult hippocampus GAGs. Structural alterations in GAGs from elderly were suggested by differential transcripts levels of key biosynthetic enzymes. C5-epimerase and 2-OST expressions were decreased while NDST-2 and 3-OST-4 were increased; in contrast, heparanase expression was unchanged. Results suggest that alteration of GAGs in hippocampus of aged subjects could participate to tissue impairment during aging. PMID:22035591

  10. Similarity in form and function of the hippocampus in rodents, monkeys, and humans

    PubMed Central

    Clark, Robert E.; Squire, Larry R.

    2013-01-01

    We begin by describing an historical scientific debate in which the fundamental idea that species are related by evolutionary descent was challenged. The challenge was based on supposed neuroanatomical differences between humans and other primates with respect to a structure known then as the hippocampus minor. The debate took place in the early 1860s, just after the publication of Darwin’s famous book. We then recount the difficult road that was traveled to develop an animal model of human memory impairment, a matter that also turned on questions about similarities and differences between humans and other primates. We then describe how the insight that there are multiple memory systems helped to secure the animal model and how the animal model was ultimately used to identify the neuroanatomy of long-term declarative memory (sometimes termed explicit memory). Finally, we describe a challenge to the animal model and to cross-species comparisons by considering the case of the concurrent discrimination task, drawing on findings from humans and monkeys. We suggest that analysis of such cases, based on the understanding that there are multiple memory systems with different properties, has served to emphasize the similarities in memory function across mammalian species. PMID:23754372

  11. Effects of inflammation on hippocampus and substantia nigra responses to novelty in healthy human participants.

    PubMed

    Harrison, Neil A; Cercignani, Mara; Voon, Valerie; Critchley, Hugo D

    2015-03-01

    Humans are naturally inquisitive. This tendency is adaptive, aiding identification of potentially valuable novel outcomes. The dopaminergic substantia nigra (SN) is implicated in the drive to explore novel stimuli and situations. However, infection and inflammation inhibit the motivation to seek out novelty. This likely serves to limit exposure to uncertain, potentially detrimental outcomes when metabolic resources are limited. Nevertheless, the neural mechanisms through which inflammation constrains novelty seeking are poorly understood. We therefore scanned 16 healthy participants (6 male, mean 27.2±7.3 years), using fMRI, once following experimental inflammation (intramuscular (i.m.) typhoid vaccination) and once after placebo (i.m. saline), with the aim of characterizing effects of inflammation on neural processing of novel and familiar place, and face stimuli. We specifically tested the effects of inflammation on the hypothesized roles of SN and hippocampus in novelty processing. Typhoid vaccination evoked a nearly threefold increase in circulating pro-inflammatory cytokine (interleukin-6) levels 3 h after injection, indicating induction of mild systemic inflammation. Enhanced hippocampal responses to novel (compared with familiar) stimuli were observed following both vaccine and placebo, consistent with intact central novelty detection. However, the normal bilateral reactivity of SN to stimulus novelty was significantly attenuated following inflammation. Correspondingly, inflammation also markedly impaired novelty-related functional coupling between the SN and hippocampus. These data extend previous findings of SN sensitivity to mild inflammation associated with changes in psychomotor responding, and suggest that inflammation-induced blunting of SN responses to hippocampal novelty signals may represent a plausible mechanism through which inflammation impairs motivational responses to novelty. PMID:25154706

  12. Effects of Inflammation on Hippocampus and Substantia Nigra Responses to Novelty in Healthy Human Participants

    PubMed Central

    Harrison, Neil A; Cercignani, Mara; Voon, Valerie; Critchley, Hugo D

    2015-01-01

    Humans are naturally inquisitive. This tendency is adaptive, aiding identification of potentially valuable novel outcomes. The dopaminergic substantia nigra (SN) is implicated in the drive to explore novel stimuli and situations. However, infection and inflammation inhibit the motivation to seek out novelty. This likely serves to limit exposure to uncertain, potentially detrimental outcomes when metabolic resources are limited. Nevertheless, the neural mechanisms through which inflammation constrains novelty seeking are poorly understood. We therefore scanned 16 healthy participants (6 male, mean 27.2±7.3 years), using fMRI, once following experimental inflammation (intramuscular (i.m.) typhoid vaccination) and once after placebo (i.m. saline), with the aim of characterizing effects of inflammation on neural processing of novel and familiar place, and face stimuli. We specifically tested the effects of inflammation on the hypothesized roles of SN and hippocampus in novelty processing. Typhoid vaccination evoked a nearly threefold increase in circulating pro-inflammatory cytokine (interleukin-6) levels 3 h after injection, indicating induction of mild systemic inflammation. Enhanced hippocampal responses to novel (compared with familiar) stimuli were observed following both vaccine and placebo, consistent with intact central novelty detection. However, the normal bilateral reactivity of SN to stimulus novelty was significantly attenuated following inflammation. Correspondingly, inflammation also markedly impaired novelty-related functional coupling between the SN and hippocampus. These data extend previous findings of SN sensitivity to mild inflammation associated with changes in psychomotor responding, and suggest that inflammation-induced blunting of SN responses to hippocampal novelty signals may represent a plausible mechanism through which inflammation impairs motivational responses to novelty. PMID:25154706

  13. Hippocampus, perirhinal cortex, and complex visual discriminations in rats and humans

    PubMed Central

    Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.

    2015-01-01

    Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with perirhinal lesions were impaired and did not exhibit the normal preference for exploring the odd object. Notably, rats with hippocampal lesions exhibited the same impairment. Thus, the deficit is unlikely to illuminate functions attributed specifically to perirhinal cortex. Both lesion groups were able to acquire visual discriminations involving the same objects used in the oddity task. Patients with hippocampal damage or larger medial temporal lobe lesions were intact in a similar oddity task that allowed participants to explore objects quickly using eye movements. We suggest that humans were able to rely on an intact working memory capacity to perform this task, whereas rats (who moved slowly among the objects) needed to rely on long-term memory. PMID:25593294

  14. Epileptic activity outlasts disinhibition after intrahippocampal tetanus toxin in the rat.

    PubMed Central

    Whittington, M A; Jefferys, J G

    1994-01-01

    1. A single dose of tetanus toxin, injected under anaesthesia into one dorsal hippocampus of the rat, produces chronic epileptic foci involving both hippocampi. Generalized seizures occurred 1-6 weeks after injection and epileptic discharges were found in hippocampal slices in vitro. Here we measured the time course of decay of epileptic activity and the level of GABAA receptor-mediated inhibition in hippocampal slices 1-16 weeks after toxin injection in vivo. 2. Epileptic activity peaked in the dentate granule cell and CA3 pyramidal cell layers 2 weeks after toxin injection and at 4 weeks in CA1. Thresholds for evoking epileptic activity were lowest in the suprapyramidal blade of the dentate gyrus and area CA3c. Recovery from epileptic activity occurred more rapidly in the contralateral hippocampus. Polyspike activity ceased by 8 weeks and interictal activity by 16 weeks. Epileptic discharges could still be evoked from CA1 16 weeks after toxin injection. 3. The maximal monosynaptic fast inhibitory postsynaptic current (IPSC) conductance changes (gIPSC) decreased to < 10% of control values at the time of peak epileptic activity and remained lower than controls for 4 weeks ipsilaterally. In the contralateral hippocampus, gIPSC fell to ca 50% of control values for the first 2 weeks. Responses to exogenous GABA remained unchanged. 4. After 8 weeks dentate granule cells had gIPSC significantly larger than controls. No increase in gIPSC occurred in CA3. Epileptic activity persisted 8-10 weeks after recovery from disinhibition ipsilaterally and 4 weeks contralaterally. 5. Epileptic activity was seen when monosynaptic GABAA receptor-mediated IPSCs were normal or supranormal. At these times polysynaptic inhibition was still profoundly reduced. These observations provide strong evidence for long-term changes in the pattern of synaptic excitation contributing to a chronic epileptic syndrome syndrome following disinhibitory insult, and are consistent with weakened excitation

  15. Functional cross-hemispheric shift between object-place paired associate memory and spatial memory in the human hippocampus.

    PubMed

    Lee, Choong-Hee; Ryu, Jungwon; Lee, Sang-Hun; Kim, Hakjin; Lee, Inah

    2016-08-01

    The hippocampus plays critical roles in both object-based event memory and spatial navigation, but it is largely unknown whether the left and right hippocampi play functionally equivalent roles in these cognitive domains. To examine the hemispheric symmetry of human hippocampal functions, we used an fMRI scanner to measure BOLD activity while subjects performed tasks requiring both object-based event memory and spatial navigation in a virtual environment. Specifically, the subjects were required to form object-place paired associate memory after visiting four buildings containing discrete objects in a virtual plus maze. The four buildings were visually identical, and the subjects used distal visual cues (i.e., scenes) to differentiate the buildings. During testing, the subjects were required to identify one of the buildings when cued with a previously associated object, and when shifted to a random place, the subject was expected to navigate to the previously chosen building. We observed that the BOLD activity foci changed from the left hippocampus to the right hippocampus as task demand changed from identifying a previously seen object (object-cueing period) to searching for its paired-associate place (object-cued place recognition period). Furthermore, the efficient retrieval of object-place paired associate memory (object-cued place recognition period) was correlated with the BOLD response of the left hippocampus, whereas the efficient retrieval of relatively pure spatial memory (spatial memory period) was correlated with the right hippocampal BOLD response. These findings suggest that the left and right hippocampi in humans might process qualitatively different information for remembering episodic events in space. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27009679

  16. Wavelet analysis of epileptic spikes

    NASA Astrophysics Data System (ADS)

    Latka, Miroslaw; Was, Ziemowit; Kozik, Andrzej; West, Bruce J.

    2003-05-01

    Interictal spikes and sharp waves in human EEG are characteristic signatures of epilepsy. These potentials originate as a result of synchronous pathological discharge of many neurons. The reliable detection of such potentials has been the long standing problem in EEG analysis, especially after long-term monitoring became common in investigation of epileptic patients. The traditional definition of a spike is based on its amplitude, duration, sharpness, and emergence from its background. However, spike detection systems built solely around this definition are not reliable due to the presence of numerous transients and artifacts. We use wavelet transform to analyze the properties of EEG manifestations of epilepsy. We demonstrate that the behavior of wavelet transform of epileptic spikes across scales can constitute the foundation of a relatively simple yet effective detection algorithm.

  17. Pyramidal neurons in the septal and temporal CA1 field of the human and hedgehog tenrec hippocampus.

    PubMed

    Liagkouras, Ioannis; Michaloudi, Helen; Batzios, Christos; Psaroulis, Dimitrios; Georgiadis, Marios; Künzle, Heinz; Papadopoulos, Georgios C

    2008-07-01

    The present study examines comparatively the cellular density of disector-counted/Nissl-stained CA1 pyramidal neurons and the morphometric characteristics (dendritic number/length, spine number/density and Sholl-counted dendritic branch points/20 microm) of the basal and apical dendritic systems of Golgi-impregnated CA1 neurons, in the septal and temporal hippocampus of the human and hedgehog tenrec brain. The obtained results indicate that in both hippocampal parts the cellular density of the CA1 pyramidal neurons is lower in human than in tenrec. However, while the human pyramidal cell density is higher in the septal hippocampal part than in the temporal one, in the tenrec the density of these cells is higher in the temporal part. The dendritic tree of the CA1 pyramidal cells, more developed in the septal than in temporal hippocampus in both species studied, is in general more complex in the human hippocampus. The basal and the apical dendritic systems exhibit species related morphometric differences, while dendrites of different orders exhibit differences in their number and length, and in their spine density. Finally, in both species, as well as hippocampal parts and dendritic systems, changes of dendritic morphometric features along ascending dendritic orders fluctuate in a similar way, as do the number of dendritic branch points in relation to the distance from the neuron soma. PMID:18511020

  18. CA1 neurons in the human hippocampus are critical for autobiographical memory, mental time travel, and autonoetic consciousness

    PubMed Central

    Bartsch, Thorsten; Döhring, Juliane; Rohr, Axel; Jansen, Olav; Deuschl, Günther

    2011-01-01

    Autobiographical memories in our lives are critically dependent on temporal lobe structures. However, the contribution of CA1 neurons in the human hippocampus to the retrieval of episodic autobiographical memory remains elusive. In patients with a rare acute transient global amnesia, highly focal lesions confined to the CA1 field of the hippocampus can be detected on MRI. We studied the effect of these lesions on autobiographical memory using a detailed autobiographical interview including the remember/know procedure. In 14 of 16 patients, focal lesions in the CA1 sector of the hippocampal cornu ammonis were detected. Autobiographical memory was significantly affected over all time periods, including memory for remote periods. Impairment of episodic memory and autonoetic consciousness exhibited a strong temporal gradient extending 30 to 40 y into the past. These results highlight the distinct and critical role of human hippocampal CA1 neurons in autobiographical memory retrieval and for re-experiencing detailed episodic memories. PMID:21987814

  19. The representation of space and the hippocampus in rats, robots and humans.

    PubMed

    Burgess, N; Donnett, J G; O'Keefe, J

    1998-01-01

    Experimental evidence suggests that the hippocampus represents locations within an allocentric representation of space. The environmental inputs that underlie the rat's representation of its own location within an environment (in the firing of place cells) are the distances to walls, and different walls are identified by their allocentric direction from the rat. We propose that the locations of goals in an environment is stored downstream of the place cells, in the subiculum. In addition to firing rate coding, place cells may use phase coding relative to the theta rhythm of the EEG. In some circumstances path integration may be used, in addition to environmental information, as an input to the hippocampal system. A detailed computational model of the hippocampus successfully guides the navigation of a mobile robot. The model's behaviour is compared to electrophysiological and behavioural data in rats, and implications for the role of the hippocampus in primates are explored. PMID:9755509

  20. The human myosin light chain kinase (MLCK) from hippocampus: Cloning, sequencing, expression, and localization to 3qcen-q21

    SciTech Connect

    Potier, M.C.; Rossier, J.; Turnell, W.G.; Pekarsky, Y.; Gardiner, K.

    1995-10-10

    Myosin light chain kinase (MLCK), a key enzyme in muscle contraction, has been shown by immunohistology to be present in neurons and glia. We describe here the cloning of the cDNA for human MLCK from hippocampus, encoding a protein sequence 95% similar to smooth muscle MLCKs but less than 60% similar to skeletal muscle MLCKs. The cDNA clone detected two RNA transcripts in human frontal and entorhinal cortex, in hippocampus, and in jejunum, one corresponding to MLCK and the other probably to telokin, the carboxy-terminal 154 codons of MLCK expressed as an independent protein in smooth muscle. Levels of expression were lower in brain compared to smooth muscle. We show that within the protein sequence, a motif of 28 or 24 residues is repeated five times, the second repeat ending with the putative methionine start codon. These repeats overlap with a second previously reported module of 12 residues repeated five times in the human sequence. In addition, the acidic C-terminus of all MLCKs from both brain and smooth muscle resembles the C-terminus of tubulins. The chromosomal localization of the gene for human MLCK is shown to be at 3qcen-q21, as determined by PCR and Southern blotting using two somatic cell hybrid panels. 33 refs., 8 figs.

  1. Slow-Theta-to-Gamma Phase-Amplitude Coupling in Human Hippocampus Supports the Formation of New Episodic Memories.

    PubMed

    Lega, Bradley; Burke, John; Jacobs, Joshua; Kahana, Michael J

    2016-01-01

    Phase-amplitude coupling (PAC) has been proposed as a neural mechanism for coordinating information processing across brain regions. Here we sought to characterize PAC in the human hippocampus, and in temporal and frontal cortices, during the formation of new episodic memories. Intracranial recordings taken as 56 neurosurgical patients studied and recalled lists of words revealed significant hippocampal PAC, with slow-theta activity (2.5-5 Hz) modulating gamma band activity (34-130 Hz). Furthermore, a significant number of hippocampal electrodes exhibited greater PAC during successful than unsuccessful encoding, with the gamma activity at these sites coupled to the trough of the slow-theta oscillation. These same conditions facilitate LTP in animal models, providing a possible mechanism of action for this effect in human memory. Uniquely in the hippocampus, phase preference during item encoding exhibited a biphasic pattern. Overall, our findings help translate between the patterns identified during basic memory tasks in animals and those present during complex human memory encoding. We discuss the unique properties of human hippocampal PAC and how our findings relate to influential theories of information processing based on theta-gamma interactions. PMID:25316340

  2. Analysis of epileptic seizures with complex network.

    PubMed

    Ni, Yan; Wang, Yinghua; Yu, Tao; Li, Xiaoli

    2014-01-01

    Epilepsy is a disease of abnormal neural activities involving large area of brain networks. Until now the nature of functional brain network associated with epilepsy is still unclear. Recent researches indicate that the small world or scale-free attributes and the occurrence of highly clustered connection patterns could represent a general organizational principle in the human brain functional network. In this paper, we seek to find whether the small world or scale-free property of brain network is correlated with epilepsy seizure formation. A mass neural model was adopted to generate multiple channel EEG recordings based on regular, small world, random, and scale-free network models. Whether the connection patterns of cortical networks are directly associated with the epileptic seizures was investigated. The results showed that small world and scale-free cortical networks are highly correlated with the occurrence of epileptic seizures. In particular, the property of small world network is more significant during the epileptic seizures. PMID:25147576

  3. [Unusual dreams in epileptics].

    PubMed

    Boldyrev, A I

    1984-01-01

    The author discusses bizarre dreams characteristic of epileptics and never occurring in normal subjects which have an important practical implication especially for early detection of epilepsy and the prevention of severe forms of the disease. This group of dreams includes vivid nightmares with vital fear, dreams not infrequently transforming into pro-dream states; persistently repeated stereotyped dreams and dreams with invariably the same unpleasant sensations representing an isolated aura of subsequent epileptic attacks. Diagnostically important may also be dreams with the symptoms of derealization and depersonalization, vague dream images and the deja vu phenomenon. PMID:6464602

  4. β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation

    PubMed Central

    Mander, Bryce A.; Marks, Shawn M.; Vogel, Jacob W.; Rao, Vikram; Lu, Brandon; Saletin, Jared M.; Ancoli-Israel, Sonia; Jagust, William J.; Walker, Matthew P.

    2015-01-01

    Independent evidence associates β-amyloid pathology with both NREM sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here, we show that β-amyloid burden within medial prefrontal cortex (mPFC) is significantly correlated with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation is not direct, but instead, statistically depends on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a novel mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly. PMID:26030850

  5. The hippocampus is required for short-term topographical memory in humans

    PubMed Central

    Hartley, Tom; Bird, Chris M.; Chan, Dennis; Cipolotti, Lisa; Husain, Masud; Vargha-Khadem, Faraneh; Burgess, Neil

    2009-01-01

    The hippocampus plays a crucial role within the neural systems for long-term memory, but little if any role in the short-term retention of some types of stimuli. Nonetheless, the hippocampus may be specialized for allocentric topographical processing which impacts on short-term memory or even perception. To investigate this we developed performance-matched tests of perception (match-to-sample) and short-term memory (2s delayed-match-to-sample) for the topography and for the non-spatial aspects of visual scenes. Four patients with focal hippocampal damage and one with more extensive damage, including right parahippocampal gyrus, were tested. All five patients showed impaired topographical memory and spared non-spatial processing in both memory and perception. Topographical perception was profoundly impaired in the patient with parahippocampal damage, mildly impaired in two of the hippocampal cases and clearly preserved in the other two hippocampal cases (including one with dense amnesia). Our results suggest that the hippocampus supports allocentric topographical processing that is indispensable when appropriately tested after even very short delays, while the presence of the sample scene can allow successful topographical perception without it, possibly via a less flexible parahippocampal representation. PMID:17143905

  6. β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation.

    PubMed

    Mander, Bryce A; Marks, Shawn M; Vogel, Jacob W; Rao, Vikram; Lu, Brandon; Saletin, Jared M; Ancoli-Israel, Sonia; Jagust, William J; Walker, Matthew P

    2015-07-01

    Independent evidence associates β-amyloid pathology with both non-rapid eye movement (NREM) sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here we show that β-amyloid burden in medial prefrontal cortex (mPFC) correlates significantly with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation was not direct, but instead statistically depended on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly. PMID:26030850

  7. Virtual water maze learning in human increases functional connectivity between posterior hippocampus and dorsal caudate.

    PubMed

    Woolley, Daniel G; Mantini, Dante; Coxon, James P; D'Hooge, Rudi; Swinnen, Stephan P; Wenderoth, Nicole

    2015-04-01

    Recent work has demonstrated that functional connectivity between remote brain regions can be modulated by task learning or the performance of an already well-learned task. Here, we investigated the extent to which initial learning and stable performance of a spatial navigation task modulates functional connectivity between subregions of hippocampus and striatum. Subjects actively navigated through a virtual water maze environment and used visual cues to learn the position of a fixed spatial location. Resting-state functional magnetic resonance imaging scans were collected before and after virtual water maze navigation in two scan sessions conducted 1 week apart, with a behavior-only training session in between. There was a large significant reduction in the time taken to intercept the target location during scan session 1 and a small significant reduction during the behavior-only training session. No further reduction was observed during scan session 2. This indicates that scan session 1 represented initial learning and scan session 2 represented stable performance. We observed an increase in functional connectivity between left posterior hippocampus and left dorsal caudate that was specific to scan session 1. Importantly, the magnitude of the increase in functional connectivity was correlated with offline gains in task performance. Our findings suggest cooperative interaction occurs between posterior hippocampus and dorsal caudate during awake rest following the initial phase of spatial navigation learning. Furthermore, we speculate that the increase in functional connectivity observed during awake rest after initial learning might reflect consolidation-related processing. PMID:25418860

  8. Dose Response Effects of Dermally applied Diethanolamine on Neurogenesis in Fetal Mouse Hippocampus and Potential Exposure of Humans

    PubMed Central

    Craciunescu, Corneliu N.; Niculescu, Mihai D.; Guo, Zhong; Johnson, Amy R.; Fischer, Leslie; Zeisel, Steven H.

    2009-01-01

    Diethanolamine (DEA) is a common ingredient of personal care products. Dermal administration of DEA diminishes hepatic stores of the essential nutrient choline and alters brain development. We previously reported that 80 mg/kg/day of DEA during pregnancy in mice reduced neurogenesis and increased apoptosis in the fetal hippocampus. This study was designed to establish the dose-response relationships for this effect of DEA. Timed-pregnant C57BL/6 mouse dams were dosed dermally from gestation day 7–17 with DEA at 0 (controls), 5, 40, 60, and 80 mg/kg body/day. Fetuses (embryonic day 17 [E17]) from dams treated dermally with 80 mg/kg body/day DEA had decreased neural progenitor cell mitosis at the ventricular surface of the ventricular zone (hippocampus, 54.1 ± 5.5%; cortex, 58.9 ± 6.8%; compared to controls; p < 0.01). Also, this dose of DEA to dams increased rates of apoptosis in E17 fetal hippocampus (to 177.2 ± 21.5% of control; measured using activated caspase-3; p < 0.01). This dose of DEA resulted in accumulation of DEA and its metabolites in liver and in plasma. At doses of DEA less than 80 mg/kg body/day to dams, there were no differences between treated and control groups. In a small group of human subjects, dermal treatment for 1 month with a commercially available skin lotion containing 1.8 mg DEA per gram resulted in detectable plasma concentrations of DEA and dimethyldiethanolamine, but these were far below those concentrations associated with perturbed brain development in the mouse. PMID:18948303

  9. Treatment of epileptic encephalopathies.

    PubMed

    McTague, Amy; Cross, J Helen

    2013-03-01

    Epileptic encephalopathy is defined as a condition where the epileptic activity itself may contribute to the severe neurological and cognitive impairment seen, over and above that which would be expected from the underlying pathology alone. The epilepsy syndromes at high risk of this are a disparate group of conditions characterized by epileptic seizures that are difficult to treat and developmental delay. In this review, we discuss the ongoing debate regarding the significance of inter-ictal discharges and the impact of the seizures themselves on the cognitive delay or regression that is a common feature of these syndromes. The syndromes also differ in many ways and we provide a summary of the key features of the early-onset epileptic encephalopathies including Ohtahara and West syndromes in addition to later childhood-onset syndromes such as Lennox Gastaut and Doose syndromes. An understanding of the various severe epilepsy syndromes is vital to understanding the rationale for treatment. For example, the resolution of hypsarrhythmia in West syndrome is associated with an improvement in cognitive outcome and drives treatment choice, but the same cannot be applied to frequent inter-ictal discharges in Lennox Gastaut syndrome. We discuss the evidence base for treatment where it is available and describe current practice where it is not. For example, in West syndrome there is some evidence for preference of hormonal treatments over vigabatrin, although the choice and duration of hormonal treatment remains unclear. We describe the use of conventional and newer anti-epileptic medications in the various syndromes and discuss which medications should be avoided. Older possibly forgotten treatments such as sulthiame and potassium bromide also have a role in the severe epilepsies of childhood. We discuss hormonal treatment with particular focus on the treatment of West syndrome, continuous spike wave in slow wave sleep (CSWS)/electrical status epilepticus in slow wave

  10. Human hippocampal theta activity during virtual navigation.

    PubMed

    Ekstrom, Arne D; Caplan, Jeremy B; Ho, Emily; Shattuck, Kirk; Fried, Itzhak; Kahana, Michael J

    2005-01-01

    This study examines whether 4-8-Hz theta oscillations can be seen in the human hippocampus, and whether these oscillations increase during virtual movement and searching, as they do in rodents. Recordings from both hippocampal and neocortical depth electrodes were analyzed while six epileptic patients played a virtual taxi-driver game. During the game, the patients alternated between searching for passengers, whose locations were random, and delivering them to stores, whose locations remained constant. In both hippocampus and neocortex, theta increased during virtual movement in all phases of the game. Hippocampal and neocortical theta activity were also significantly correlated with each other, but this correlation did not differ between neocortex and hippocampus and within disparate neocortical electrodes. Our findings demonstrate the existence of movement-related theta oscillations in human hippocampus, and suggest that both cortical and hippocampal oscillations play a role in attention and sensorimotor integration. PMID:16114040

  11. Evaluation of cytochrome P450 inductions by anti-epileptic drug oxcarbazepine, 10-hydroxyoxcarbazepine, and carbamazepine using human hepatocytes and HepaRG cells.

    PubMed

    Sugiyama, Ikuo; Murayama, Norie; Kuroki, Ayaka; Kota, Jagannath; Iwano, Shunsuke; Yamazaki, Hiroshi; Hirota, Takashi

    2016-09-01

    Anti-epileptic drug oxcarbazepine is structurally related to carbamazepine, but has reportedly different metabolic pathway. Auto-induction potentials of oxcarbazepine, its pharmacologically active metabolite 10-hydroxyoxcarbazepine and carbamazepine were evaluated by cytochrome P450 (CYP) 1A2, CYP2B6 and CYP3A4 mRNA levels and primary metabolic rates using human hepatocytes and HepaRG cells. For the CYP1A2 the induction potential determined as the fold change in mRNA levels was 7.2 (range: 2.3-11.5) and 10.0 (6.2-13.7) for oxcarbazepine and carbamazepine, respectively, while 10-hydroxyoxcarbazepine did not induce. The fold change in mRNA levels for CYP2B6 was 11.5 (3.2-19.3), 7.0 (2.5-10.8) and 14.8 (3.1-29.1) for oxcarbazepine, 10-hydroxyoxcarbazepine and carbamazepine, respectively. The fold change for CYP3A4 induction level by oxcarbazepine, 10-hydroxyoxcarbazepine and carbamazepine was 3.5 (1.2-7.4), 2.7 (0.8-5.7) and 8.3 (3.5-14.5), respectively. The data suggest lower induction potential of oxcarbazepine and 10-hydroxyoxcarbazepine relative to carbamazepine. The results in HepaRG cells showed similar trend as the human hepatocytes. After incubation for 72 h in hepatocytes and HepaRG cells, auto-induction was evident for only carbamazepine metabolism. The 10-keto group instead of double bond at C10 position is evidently a determinant factor for limited auto-induction of P450 enzymes by oxcarbazepine. PMID:26711482

  12. Increased stathmin expression strengthens fear conditioning in epileptic rats.

    PubMed

    Zhang, Linna; Feng, Danni; Tao, Hong; DE, Xiangyan; Chang, Qing; Hu, Qikuan

    2015-01-01

    Patients with temporal lobe epilepsy have inexplicable fear attack as the aura. However, the underlying neural mechanisms of seizure-modulated fear are not clarified. Recent studies identified stathmin as one of the key controlling molecules in learning and innate fear. Stathmin binds to tubulin, inhibits microtubule assembly and promotes microtubule catastrophes. Therefore, stathmin is predicted to play a crucial role in the association of epilepsy seizures with fear conditioning. Firstly, a pilocarpine model of epilepsy in rats was established, and subsequently the fear condition training was performed. The epileptic rats with fear conditioning (epilepsy + fear) had a much longer freezing time compared to each single stimulus. The increased freezing levels revealed a significantly strengthened effect of the epileptic seizures on the learned fear of the tone-shock contextual. Subsequently, the stathmin expression was compared in the hippocampus, the amygdale, the insular cortex and the temporal lobe. The significant change of stathmin expression occurred in the insular and the hippocampus, but not in the amygdale. Stathmin expression and dendritic microtubule stability were compared between fear and epilepsy in rats. Epilepsy was found to strengthen the fear conditioning with increased expression of stathmin and a decrease in microtubule stability. Fear conditioning slightly increased the expression of stathmin, whereas epilepsy with fear conditioning increased it significantly in the hippocampus, insular cortex and hypothalamus. The phosphorylated stathmin slightly increased in the epilepsy with fear conditioning. The increased expression of stathmin was contrary to the decrease of the stathmin microtubule-associated protein (MAP2) and α-tubulin in the epileptic rats with fear conditioning in all three areas of the brain. The most significant change of the ratio of MAP2 and α-tubulin/stathmin occurred in the insular cortex and hippocampus. In conclusion

  13. The rat brain hippocampus proteome.

    PubMed

    Fountoulakis, Michael; Tsangaris, George T; Maris, Antony; Lubec, Gert

    2005-05-01

    The hippocampus is crucial in memory storage and retrieval and plays an important role in stress response. In humans, the CA1 area of hippocampus is one of the first brain areas to display pathology in Alzheimer's disease. A comprehensive analysis of the hippocampus proteome has not been accomplished yet. We applied proteomics technologies to construct a two-dimensional database for rat brain hippocampus proteins. Hippocampus samples from eight months old animals were analyzed by two-dimensional electrophoresis and the proteins were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The database comprises 148 different gene products, which are in the majority enzymes, structural proteins and heat shock proteins. It also includes 39 neuron specific gene products. The database may be useful in animal model studies of neurological disorders. PMID:15797529

  14. Monocarboxylate Transporter 1 is Deficient on Microvessels in the Human Epileptogenic Hippocampus

    PubMed Central

    Lauritzen, Fredrik; de Lanerolle, Nihal C.; Lee, Tih-Shih W.; Spencer, Dennis D.; Kim, Jung H.; Bergersen, Linda H.; Eid, Tore

    2010-01-01

    Monocarboxylate transporter 1 (MCT1) facilitates the transport of important metabolic fuels (lactate, pyruvate and ketone bodies) and possibly also acidic drugs such as valproic acid across the blood brain barrier. Because an impaired brain energy metabolism and resistance to antiepileptic drugs are common features of temporal lobe epilepsy (TLE), we sought to study the expression of MCT1 in the brain of patients with this disease. Immunohistochemistry and immunogold electron microscopy were used to assess the distribution of MCT1 in brain specimens from patients with TLE and concomitant hippocampal sclerosis (referred to as mesial TLE or MTLE (n = 15)), patients with TLE and no hippocampal sclerosis (non-MTLE, n = 13) and neurologically normal autopsy subjects (n = 8). MCT1 was present on an extensive network of microvessels throughout the hippocampal formation in autopsy controls and to a lesser degree in non-MTLE. Patients with MTLE were markedly deficient in MCT1 on microvessels in several areas of the hippocampal formation, especially CA1, which exhibited a 37 to 48% loss of MCT1 on the plasma membrane of endothelial cells when compared with non-MTLE. These findings suggest that the uptake of blood-derived monocarboxylate fuels and possibly also acidic drugs, such as valproic acid, is perturbed in the epileptogenic hippocampus, particularly in MTLE. We hypothesize that the loss of MCT1 on brain microvessels is mechanistically involved in the pathophysiology of drug-resistant TLE, and propose that re-expression of MCT1 may represent a novel therapeutic approach for this disease. PMID:21081165

  15. Imaging of copper, zinc, and other elements in thin section of human brain samples (hippocampus) by laser ablation inductively coupled plasma mass spectrometry.

    PubMed

    Becker, J S; Zoriy, M V; Pickhardt, C; Palomero-Gallagher, N; Zilles, K

    2005-05-15

    Laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) was used to produce images of element distribution in 20-microm thin sections of human brain tissue. The sample surface was scanned (raster area approximately 80 mm(2)) with a focused laser beam (wavelength 213 nm, diameter of laser crater 50 microm, and laser power density 3 x 10(9) W cm(-2)) in a cooled laser ablation chamber developed for these measurements. The laser ablation system was coupled to a double-focusing sector field ICPMS. Ion intensities of 31P+, 32S+, 56Fe+, 63Cu+, 64Zn+, 232Th+, and 238U+ were measured within the area of interest of the human brain tissue (hippocampus) by LA-ICPMS. The quantitative determination of copper, zinc, uranium, and thorium distribution in thin slices of the human hippocampus was performed using matrix-matched laboratory standards. In addition, a new arrangement in solution-based calibration using a micronebulizer, which was inserted directly into the laser ablation chamber, was applied for validation of synthetic laboratory standard. The mass spectrometric analysis yielded an inhomogeneous distribution (layered structure) for P, S, Cu, and Zn in thin brain sections of the hippocampus. In contrast, Th and U are more homogeneously distributed at a low-concentration level with detection limits in the low-nanogram per gram range. The unique analytical capability and the limits of LA-ICPMS will be demonstrated for the imaging of element distribution in thin cross sections of brain tissue from the hippocampus. LA-ICPMS provides new information on the spatial element distribution of the layered structure in thin sections of brain tissues from the hippocampus. PMID:15889910

  16. The role of the hippocampus in approach-avoidance conflict decision-making: Evidence from rodent and human studies.

    PubMed

    Ito, Rutsuko; Lee, Andy C H

    2016-10-15

    The hippocampus (HPC) has been traditionally considered to subserve mnemonic processing and spatial cognition. Over the past decade, however, there has been increasing interest in its contributions to processes beyond these two domains. One question is whether the HPC plays an important role in decision-making under conditions of high approach-avoidance conflict, a scenario that arises when a goal stimulus is simultaneously associated with reward and punishment. This idea has its origins in rodent work conducted in the 1950s and 1960s, and has recently experienced a resurgence of interest in the literature. In this review, we will first provide an overview of classic rodent lesion data that first suggested a role for the HPC in approach-avoidance conflict processing and then proceed to describe a wide range of more recent evidence from studies conducted in rodents and humans. We will demonstrate that there is substantial, converging cross-species evidence to support the idea that the HPC, in particular the ventral (in rodents)/anterior (in humans) portion, contributes to approach-avoidance conflict decision making. Furthermore, we suggest that the seemingly disparate functions of the HPC (e.g. memory, spatial cognition, conflict processing) need not be mutually exclusive. PMID:27457133

  17. Dopamine D2 receptor expression in hippocampus and parahippocampal cortex of rat, cat, and human in relation to tyrosine hydroxylase-immunoreactive fibers.

    PubMed

    Goldsmith, S K; Joyce, J N

    1994-06-01

    A detailed study comparing the distribution of D2 receptors and tyrosine hydroxylase-immunoreactive fibers in the hippocampus and parahippocampal cortices of the rat, cat, and human was conducted. The distribution of [125I]epidepride binding to D2 receptors along the transverse and longitudinal axes of the hippocampus and parahippocampus differed among the species. In rat hippocampus, the number of sites was highest in septal portions of lacunosum-moleculare of CA1 and stratum moleculare of the subiculum. Virtually no binding to D2 receptors existed in the temporal hippocampus. For the cat hippocampus, the highest binding existed in the inner one-third of the molecular layer of the dentate gyrus (DG). There were also significant numbers of D2 receptors in strata radiatum and oriens of the CA subfields, with almost undetectable levels in lacunosum moleculare and subiculum. The number of sites was higher in the septal than temporal hippocampus. In the human hippocampus, highest binding was observed in the molecular layer of DG and the subiculum, with lower levels in strata oriens and lacunosum-moleculare of CA3, and very low binding in CA1. The histochemical demonstration of the pattern of mossy fibers revealed an organization complementary to that of D2 receptors in cat and human. In none of the species was there significant expression of D2 receptors in the entorhinal cortex, except in the caudal extreme of this region in the rat. In that region a trilaminar pattern was exhibited that continued into the perirhinal cortex. A trilaminar pattern of D2 receptor expression was observed in the perirhinal cortex of all species, with the highest values in the external and deep laminae and low expression in the middle laminae. The organization of dopamine fibers was assessed by comparing the distribution of tyrosine hydroxylase-positive and dopamine beta-hydroxylase-immunoreactive fibers in these same regions. It revealed consistent mismatches between the pattern of D2

  18. In vivo detection of epileptic brain tissue using static fluorescence and diffuse reflectance spectroscopy

    NASA Astrophysics Data System (ADS)

    Yadav, Nitin; Bhatia, Sanjiv; Ragheb, John; Mehta, Rupal; Jayakar, Prasanna; Yong, William; Lin, Wei-Chiang

    2013-02-01

    Diffuse reflectance and fluorescence spectroscopy are used to detect histopathological abnormalities of an epileptic brain in a human subject study. Static diffuse reflectance and fluorescence spectra are acquired from normal and epileptic brain areas, defined by electrocorticography (ECoG), from pediatric patients undergoing epilepsy surgery. Biopsy specimens are taken from the investigated sites within an abnormal brain. Spectral analysis reveals significant differences in diffuse reflectance spectra and the ratio of fluorescence and diffuse reflectance spectra from normal and epileptic brain areas defined by ECoG and histology. Using these spectral differences, tissue classification models with accuracy above 80% are developed based on linear discriminant analysis. The differences between the diffuse reflectance spectra from the normal and epileptic brain areas observed in this study are attributed to alterations in the static hemodynamic characteristics of an epileptic brain, suggesting a unique association between the histopathological and the hemodynamic abnormalities in an epileptic brain.

  19. De novo mutations in epileptic encephalopathies.

    PubMed

    Allen, Andrew S; Berkovic, Samuel F; Cossette, Patrick; Delanty, Norman; Dlugos, Dennis; Eichler, Evan E; Epstein, Michael P; Glauser, Tracy; Goldstein, David B; Han, Yujun; Heinzen, Erin L; Hitomi, Yuki; Howell, Katherine B; Johnson, Michael R; Kuzniecky, Ruben; Lowenstein, Daniel H; Lu, Yi-Fan; Madou, Maura R Z; Marson, Anthony G; Mefford, Heather C; Esmaeeli Nieh, Sahar; O'Brien, Terence J; Ottman, Ruth; Petrovski, Slavé; Poduri, Annapurna; Ruzzo, Elizabeth K; Scheffer, Ingrid E; Sherr, Elliott H; Yuskaitis, Christopher J; Abou-Khalil, Bassel; Alldredge, Brian K; Bautista, Jocelyn F; Berkovic, Samuel F; Boro, Alex; Cascino, Gregory D; Consalvo, Damian; Crumrine, Patricia; Devinsky, Orrin; Dlugos, Dennis; Epstein, Michael P; Fiol, Miguel; Fountain, Nathan B; French, Jacqueline; Friedman, Daniel; Geller, Eric B; Glauser, Tracy; Glynn, Simon; Haut, Sheryl R; Hayward, Jean; Helmers, Sandra L; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi E; Knowlton, Robert C; Kossoff, Eric H; Kuperman, Rachel; Kuzniecky, Ruben; Lowenstein, Daniel H; McGuire, Shannon M; Motika, Paul V; Novotny, Edward J; Ottman, Ruth; Paolicchi, Juliann M; Parent, Jack M; Park, Kristen; Poduri, Annapurna; Scheffer, Ingrid E; Shellhaas, Renée A; Sherr, Elliott H; Shih, Jerry J; Singh, Rani; Sirven, Joseph; Smith, Michael C; Sullivan, Joseph; Lin Thio, Liu; Venkat, Anu; Vining, Eileen P G; Von Allmen, Gretchen K; Weisenberg, Judith L; Widdess-Walsh, Peter; Winawer, Melodie R

    2013-09-12

    Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders. PMID:23934111

  20. [Genes Responsible for Epileptic Syndromes].

    PubMed

    Kato, Mitsuhiro

    2016-02-01

    The first causative gene for epileptic syndrome was revealed 20 years ago. Since then, many genes responsible for epileptic syndrome, particularly sporadic epileptic encephalopathies, such as Ohtahara syndrome, West syndrome, and focal cortical dysplasia, have been identified. Although epilepsy was recognized as a channelopathy in the beginning stages of gene discovery, other molecular mechanisms for epileptic syndromes, such as interneuronopathy, synaptic vesicle release, and mTOR signal transduction, are emerging. A new technique for gene analysis using the next-generation sequencer is now available for clinical purpose abroad and precision medicine based on the molecular mechanisms has started. Infrastructural development of the official framework, from molecular diagnosis to personalized therapy, is urgently required in Japan. PMID:26873236

  1. Old and new anti-epileptic drugs in pregnancy.

    PubMed

    Regesta, G; Tanganelli, P

    2000-01-01

    During the recent years, a significant number of anti-epileptic drugs have been approved for prescription in different countries. In addition, some other promising drugs are in various stages of development. Soon after each drug has found its place in the therapeutic arsenal, pregnancies with exposure occur, with an increased risk of birth defect and developmental disturbances. As regards the possible teratogenic effect of the new anti-epileptic drugs, apart some individual reports we have only the results of pre-clinical toxicological studies which are difficult to extrapolate to the human situation, because of the well-known interspecies differences in pharmacokinetics and pharmacodynamics. Furthermore, combinations of anti-epileptic drugs are not tested pre-clinically while these new drugs are prescribed as add-on medication. So, metabolic interactions between individual components of such drug combinations may induce unexpected teratogenic effects. Also as for the teratogenic effects of the old drugs many questions have still to be defined. The most common and more important are which anti-epileptic drugs or combination of drugs is most safe for a particular woman with epilepsy and if there is an association between single anti-epileptic drugs and specific malformations. The reason is that none of the available reports to date have studied a sufficient number of women with epilepsy exposed to anti-epileptic drug monotherapy during pregnancy. Other questions concern dose-effect relationships, a universally accepted definition of major and minor malformations, and the lack of a thorough, exhaustive evaluation of the other risk factors, apart from the drugs. All these questions need to be ascertained for both the old and the new anti-epileptic drugs. Owing to these considerations, in 1998 an European Register of anti-epileptic drugs and pregnancy was instituted. The primary objective of the study is to evaluate and determine the degree of safety, with respect to

  2. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain

    PubMed Central

    Lieblein-Boff, Jacqueline C.; Johnson, Elizabeth J.; Kennedy, Adam D.; Lai, Chron-Si; Kuchan, Matthew J.

    2015-01-01

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region—specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development. PMID:26317757

  3. A neural substrate in the human hippocampus for linking successive events

    PubMed Central

    Paz, Rony; Gelbard-Sagiv, Hagar; Mukamel, Roy; Harel, Michal; Malach, Rafael; Fried, Itzhak

    2010-01-01

    Memory formation requires the placement of experienced events in the same order in which they appeared. A large body of evidence from human studies indicates that structures in the medial temporal lobe are critically involved in forming and maintaining such memories, and complementing evidence from lesion and electrophysiological work in animals support these findings. However, it remains unclear how single cells and networks of cells can signal this temporal relationship between events. Here we used recordings from single cells in the human brain obtained while subjects viewed repeated presentations of cinematic episodes. We found that neuronal activity in successive time segments became gradually correlated, and, as a result, activity in a given time window became a faithful predictor of the activity to follow. This correlation emerged rapidly, within two to three presentations of an episode and exceeded both context-independent and pure stimulus-driven correlations. The correlation was specific for hippocampal neurons, did not occur in the amygdala and anterior cingulate cortex, and was found for single cells, cell pairs, and triplets of cells, supporting the notion that cell assemblies code for the temporal relationships between sensory events. Importantly, this neuronal measure of temporal binding successfully predicted subjects’ ability to recall and verbally report the viewed episodes later. Our findings suggest a neuronal substrate for the formation of memory of the temporal order of events. PMID:20231430

  4. High field magnetic resonance microscopy of the human hippocampus in Alzheimer’s disease: quantitative imaging and correlation with iron

    PubMed Central

    Antharam, Vijay; Collingwood, Joanna F; Bullivant, John-Paul; Davidson, Mark R; Chandra, Saurav; Mikhaylova, Albina; Finnegan, Mary; Batich, Christopher; Forder, John R; Dobson, Jon

    2013-01-01

    We report R2 and R2* in human hippocampus from five unfixed post-mortem Alzheimer’s disease (AD) and three age-matched control cases. Formalin-fixed tissues from opposing hemispheres in a matched AD and control were included for comparison. Imaging was performed in a 600 MHz (14T) vertical bore magnet at MR microscopy resolution to obtain R2 and R2* (62 μm × 62 μm in-plane, 80 μm slice thickness), and R1 at 250 μm isotropic resolution. R1, R2 and R2* maps were computed for individual slices in each case, and used to compare subfields between AD and controls. The magnitudes of R2 and R2* changed very little between AD and control, but their variances in the Cornu Ammonis and dentate gyrus were significantly higher in AD compared for controls (p < 0.001). To investigate the relationship between tissue iron and MRI parameters, each tissue block was cryosectioned at 30 μm in the imaging plane, and iron distribution was mapped using synchrotron microfocus X-ray fluorescence spectroscopy. A positive correlation of R2 and R2* with iron was demonstrated. While studies with fixed tissues are more straightforward to conduct, fixation can alter iron status in tissues, making measurement of unfixed tissue relevant. To our knowledge, these data represent an advance in quantitative imaging of hippocampal subfields in unfixed tissue, and the methods facilitate direct analysis of the relationship between MRI parameters and iron. The significantly increased variance in AD compared for controls warrants investigation at lower fields and in-vivo, to determine if this parameter is clinically relevant. PMID:21867761

  5. Can structural or functional changes following traumatic brain injury in the rat predict the epileptic outcome?

    PubMed Central

    Shultz, Sandy R; Cardamone, Lisa; Liu, Ying R; Hogan, R. Edward; Maccotta, Luigi; Wright, David K; Zheng, Ping; Koe, Amelia; Gregoire, Marie-Claude; Williams, John P; Hicks, Rodney J; Jones, Nigel C; Myers, Damian E; O’Brien, Terence J; Bouilleret, Viviane

    2014-01-01

    Summary Purpose Post-traumatic epilepsy (PTE) occurs in a proportion of traumatic brain injury (TBI) cases, significantly compounding the disability, risk of injury, and death for sufferers. To date, predictive biomarkers for PTE have not been identified. This study used the lateral fluid percussion injury (LFPI) rat model of TBI to investigate whether structural, functional, and behavioral changes post-TBI relate to the later development of PTE. Methods Adult male Wistar rats underwent LFPI or sham-injury. Serial MR and PET imaging, and behavioral analyses were performed over six months post-injury. Rats were then implanted with recording electrodes and monitored for two consecutive weeks using video-EEG to assess for PTE. Of the LFPI rats, 52% (n=12) displayed spontaneous recurring seizures and/or epileptic discharges on the video-EEG recordings. Key findings MRI volumetric and signal analysis of changes in cortex, hippocampus, thalamus, and amygdala, 18F-FDG PET analysis of metabolic function, and behavioral analysis of cognitive and emotional changes, at one week, one month, three months, and six months post-LFPI, all failed to identify significant differences on univariate analysis between the epileptic and non-epileptic groups. However, hippocampal surface shape analysis using high dimensional mapping-large deformation identified significant changes in the ipsilateral hippocampus at one week post-injury relative to baseline that differed between rats that would go onto become epileptic versus those who did not. Furthermore, a multivariate logistic regression model that incorporated the one week, one month, and three month 18F-FDG PET parameters from the ipsilateral hippocampus was able to correctly predict the epileptic outcome in all of the LFPI cases. As such, these subtle changes in the ipsilateral hippocampus at acute phases after LFPI may be related to PTE and require further examination. Significance These findings suggest PTE may be independent of

  6. Multiphoton fluorescence imaging of NADH to quantify metabolic changes in epileptic tissue in vitro

    NASA Astrophysics Data System (ADS)

    Chia, Thomas H.; Zinter, Joseph; Spencer, Dennis D.; Williamson, Anne; Levene, Michael J.

    2007-02-01

    A powerful advantage of multiphoton microscopy is its ability to image endogenous fluorophores such as the ubiquitous coenzyme NADH in discrete cellular populations. NADH is integral in both oxidative and non-oxidative cellular metabolism. NADH loses fluorescence upon oxidation to NAD +; thus changes in NADH fluorescence can be used to monitor metabolism. Recent studies have suggested that hypo metabolic astrocytes play an important role in cases of temporal lobe epilepsy (TLE). Current theories suggest this may be due to defective and/or a reduced number of mitochondria or dysfunction of the neuronal-astrocytic metabolic coupling. Measuring NADH fluorescence changes following chemical stimulation enables the quantification of the cellular distribution of metabolic anomalies in epileptic brain tissue compared to healthy tissue. We present what we believe to be the first multiphoton microscopy images of NADH from the human brain. We also present images of NADH fluorescence from the hippocampus of the kainate-treated rat TLE model. In some experiments, human and rat astrocytes were selectively labeled with the fluorescent dye sulforhodamine 101 (SR101). Our results demonstrate that multiphoton microscopy is a powerful tool for assaying the metabolic pathologies associated with temporal lobe epilepsy in humans and in rodent models.

  7. Epileptic activity recognition in EEG recording

    NASA Astrophysics Data System (ADS)

    Diambra, L.; de Figueiredo, J. C. Bastos; Malta, C. P.

    1999-12-01

    We apply Approximate Entropy (ApEn) algorithm in order to recognize epileptic activity in electroencephalogram recordings. ApEn is a recently developed statistical quantity for quantifying regularity and complexity. Our approach is illustrated regarding different types of epileptic activity. In all segments associated with epileptic activity analyzed here the complexity of the signal measured by ApEn drops abruptly. This fact can be useful for automatic recognition and detection of epileptic seizures.

  8. Imaging DC MEG Fields Associated with Epileptic Onset

    NASA Astrophysics Data System (ADS)

    Weiland, B. J.; Bowyer, S. M.; Moran, J. E.; Jenrow, K.; Tepley, N.

    2004-10-01

    Magnetoencephalography (MEG) is a non-invasive brain imaging modality, with high spatial and temporal resolution, used to evaluate and quantify the magnetic fields associated with neuronal activity. Complex partial epileptic seizures are characterized by hypersynchronous neuronal activity believed to arise from a zone of epileptogenesis. This study investigated the characteristics of direct current (DC) MEG shifts arising at epileptic onset. MEG data were acquired with rats using a six-channel first order gradiometer system. Limbic status epilepticus was induced by IA (femoral) administration of kainic acid. DC-MEG shifts were observed at the onset of epileptic spike train activity and status epilepticus. Epilepsy is also being studied in patients undergoing presurgical mapping from the Comprehensive Epilepsy Center at Henry Ford Hospital using a whole head Neuromagnetometer. Preliminary data analysis shows that DC-MEG waveforms, qualitatively similar to those seen in the animal model, are evident prior to seizure activity in human subjects.

  9. Global Interactions Analysis of Epileptic ECoG Data

    NASA Astrophysics Data System (ADS)

    Ortega, Guillermo J.; Sola, Rafael G.; Pastor, Jesús

    2007-05-01

    Localization of the epileptogenic zone is an important issue in epileptology, even though there is not a unique definition of the epileptic focus. The objective of the present study is to test ultrametric analysis to uncover cortical interactions in human epileptic data. Correlation analysis has been carried out over intraoperative Electro-Corticography (ECoG) data in 2 patients suffering from temporal lobe epilepsy (TLE). Recordings were obtained using a grid of 20 electrodes (5×4) covering the lateral temporal lobe and a strip of either 4 or 8 electrodes at the mesial temporal lobe. Ultrametric analysis was performed in the averaged final correlation matrices. By using the matrix of linear correlation coefficients and the appropriate metric distance between pairs of electrodes time series, we were able to construct Minimum Spanning Trees (MST). The topological connectivity displayed by these trees gives useful and valuable information regarding physiological and pathological information in the temporal lobe of epileptic patients.

  10. Involvement of Thalamus in Initiation of Epileptic Seizures Induced by Pilocarpine in Mice

    PubMed Central

    Li, Yong-Hua; Li, Jia-Jia; Lu, Qin-Chi; Gong, Hai-Qing; Liang, Pei-Ji

    2014-01-01

    Studies have suggested that thalamus is involved in temporal lobe epilepsy, but the role of thalamus is still unclear. We obtained local filed potentials (LFPs) and single-unit activities from CA1 of hippocampus and parafascicular nucleus of thalamus during the development of epileptic seizures induced by pilocarpine in mice. Two measures, redundancy and directionality index, were used to analyze the electrophysiological characters of neuronal activities and the information flow between thalamus and hippocampus. We found that LFPs became more regular during the seizure in both hippocampus and thalamus, and in some cases LFPs showed a transient disorder at seizure onset. The variation tendency of the peak values of cross-correlation function between neurons matched the variation tendency of the redundancy of LFPs. The information tended to flow from thalamus to hippocampus during seizure initiation period no matter what the information flow direction was before the seizure. In some cases the information flow was symmetrically bidirectional, but none was found in which the information flowed from hippocampus to thalamus during the seizure initiation period. In addition, inactivation of thalamus by tetrodotoxin (TTX) resulted in a suppression of seizures. These results suggest that thalamus may play an important role in the initiation of epileptic seizures. PMID:24778885

  11. Hsp60 response in experimental and human temporal lobe epilepsy

    PubMed Central

    Gammazza, Antonella Marino; Colangeli, Roberto; Orban, Gergely; Pierucci, Massimo; Di Gennaro, Giancarlo; Bello, Margherita Lo; D'Aniello, Alfredo; Bucchieri, Fabio; Pomara, Cristoforo; Valentino, Mario; Muscat, Richard; Benigno, Arcangelo; Zummo, Giovanni; de Macario, Everly Conway; Cappello, Francesco; Di Giovanni, Giuseppe; Macario, Alberto J. L.

    2015-01-01

    The mitochondrial chaperonin Hsp60 is a ubiquitous molecule with multiple roles, constitutively expressed and inducible by oxidative stress. In the brain, Hsp60 is widely distributed and has been implicated in neurological disorders, including epilepsy. A role for mitochondria and oxidative stress has been proposed in epileptogenesis of temporal lobe epilepsy (TLE). Here, we investigated the involvement of Hsp60 in TLE using animal and human samples. Hsp60 immunoreactivity in the hippocampus, measured by Western blotting and immunohistochemistry, was increased in a rat model of TLE. Hsp60 was also increased in the hippocampal dentate gyrus neurons somata and neuropil and hippocampus proper (CA3, CA1) of the epileptic rats. We also determined the circulating levels of Hsp60 in epileptic animals and TLE patients using ELISA. The epileptic rats showed circulating levels of Hsp60 higher than controls. Likewise, plasma post-seizure Hsp60 levels in patients were higher than before the seizure and those of controls. These results demonstrate that Hsp60 is increased in both animals and patients with TLE in affected tissues, and in plasma in response to epileptic seizures, and point to it as biomarker of hippocampal stress potentially useful for diagnosis and patient management. PMID:25801186

  12. Fractal Dimension in Epileptic EEG Signal Analysis

    NASA Astrophysics Data System (ADS)

    Uthayakumar, R.

    Fractal Analysis is the well developed theory in the data analysis of non-linear time series. Especially Fractal Dimension is a powerful mathematical tool for modeling many physical and biological time signals with high complexity and irregularity. Fractal dimension is a suitable tool for analyzing the nonlinear behaviour and state of the many chaotic systems. Particularly in analysis of chaotic time series such as electroencephalograms (EEG), this feature has been used to identify and distinguish specific states of physiological function.Epilepsy is the main fatal neurological disorder in our brain, which is analyzed by the biomedical signal called Electroencephalogram (EEG). The detection of Epileptic seizures in the EEG Signals is an important tool in the diagnosis of epilepsy. So we made an attempt to analyze the EEG in depth for knowing the mystery of human consciousness. EEG has more fluctuations recorded from the human brain due to the spontaneous electrical activity. Hence EEG Signals are represented as Fractal Time Series.The algorithms of fractal dimension methods have weak ability to the estimation of complexity in the irregular graphs. Divider method is widely used to obtain the fractal dimension of curves embedded into a 2-dimensional space. The major problem is choosing initial and final step length of dividers. We propose a new algorithm based on the size measure relationship (SMR) method, quantifying the dimensional behaviour of irregular rectifiable graphs with minimum time complexity. The evidence for the suitability (equality with the nature of dimension) of the algorithm is illustrated graphically.We would like to demonstrate the criterion for the selection of dividers (minimum and maximum value) in the calculation of fractal dimension of the irregular curves with minimum time complexity. For that we design a new method of computing fractal dimension (FD) of biomedical waveforms. Compared to Higuchi's algorithm, advantages of this method include

  13. How Sleep Activates Epileptic Networks?

    PubMed Central

    Halász, Peter

    2013-01-01

    Background. The relationship between sleep and epilepsy has been long ago studied, and several excellent reviews are available. However, recent development in sleep research, the network concept in epilepsy, and the recognition of high frequency oscillations in epilepsy and more new results may put this matter in a new light. Aim. The review address the multifold interrelationships between sleep and epilepsy networks and with networks of cognitive functions. Material and Methods. The work is a conceptual update of the available clinical data and relevant studies. Results and Conclusions. Studies exploring dynamic microstructure of sleep have found important gating mechanisms for epileptic activation. As a general rule interictal epileptic manifestations seem to be linked to the slow oscillations of sleep and especially to the reactive delta bouts characterized by A1 subtype in the CAP system. Important link between epilepsy and sleep is the interference of epileptiform discharges with the plastic functions in NREM sleep. This is the main reason of cognitive impairment in different forms of early epileptic encephalopathies affecting the brain in a special developmental window. The impairment of cognitive functions via sleep is present especially in epileptic networks involving the thalamocortical system and the hippocampocortical memory encoding system. PMID:24159386

  14. A novel genetic programming approach for epileptic seizure detection.

    PubMed

    Bhardwaj, Arpit; Tiwari, Aruna; Krishna, Ramesh; Varma, Vishaal

    2016-02-01

    The human brain is a delicate mix of neurons (brain cells), electrical impulses and chemicals, known as neurotransmitters. Any damage has the potential to disrupt the workings of the brain and cause seizures. These epileptic seizures are the manifestations of epilepsy. The electroencephalograph (EEG) signals register average neuronal activity from the cerebral cortex and label changes in activity over large areas. A detailed analysis of these electroencephalograph (EEG) signals provides valuable insights into the mechanisms instigating epileptic disorders. Moreover, the detection of interictal spikes and epileptic seizures in an EEG signal plays an important role in the diagnosis of epilepsy. Automatic seizure detection methods are required, as these epileptic seizures are volatile and unpredictable. This paper deals with an automated detection of epileptic seizures in EEG signals using empirical mode decomposition (EMD) for feature extraction and proposes a novel genetic programming (GP) approach for classifying the EEG signals. Improvements in the standard GP approach are made using a Constructive Genetic Programming (CGP) in which constructive crossover and constructive subtree mutation operators are introduced. A hill climbing search is integrated in crossover and mutation operators to remove the destructive nature of these operators. A new concept of selecting the Globally Prime offspring is also presented to select the best fitness offspring generated during crossover. To decrease the time complexity of GP, a new dynamic fitness value computation (DFVC) is employed to increase the computational speed. We conducted five different sets of experiments to evaluate the performance of the proposed model in the classification of different mixtures of normal, interictal and ictal signals, and the accuracies achieved are outstandingly high. The experimental results are compared with the existing methods on same datasets, and these results affirm the potential use of

  15. Epileptic Seizure Forewarning by Nonlinear Techniques

    SciTech Connect

    Hively, L.M.

    2002-04-19

    This report describes work that was performed under a Cooperative Research and Development Agreement (CRADA) between UT-Battelle, LLC (Contractor) and a commercial participant, VIASYS Healthcare Inc. (formerly Nicolet Biomedical, Inc.). The Contractor has patented technology that forewarns of impending epileptic events via scalp electroencephalograph (EEG) data and successfully demonstrated this technology on 20 datasets from the Participant under pre-CRADA effort. This CRADA sought to bridge the gap between the Contractor's existing research-class software and a prototype medical device for subsequent commercialization by the Participant. The objectives of this CRADA were (1) development of a combination of existing computer hardware and Contractor-patented software into a clinical process for warning of impending epileptic events in human patients, and (2) validation of the epilepsy warning methodology. This work modified the ORNL research-class FORTRAN for forewarning to run under a graphical user interface (GUI). The GUI-FORTRAN software subsequently was installed on desktop computers at five epilepsy monitoring units. The forewarning prototypes have run for more than one year without any hardware or software failures. This work also reported extensive analysis of model and EEG datasets to demonstrate the usefulness of the methodology. However, the Participant recently chose to stop work on the CRADA, due to a change in business priorities. Much work remains to convert the technology into a commercial clinical or ambulatory device for patient use, as discussed in App. H.

  16. Nonlinear analysis of EEG for epileptic seizures

    SciTech Connect

    Hively, L.M.; Clapp, N.E.; Daw, C.S.; Lawkins, W.F.; Eisenstadt, M.L.

    1995-04-01

    We apply chaotic time series analysis (CTSA) to human electroencephalogram (EEG) data. Three epoches were examined: epileptic seizure, non-seizure, and transition from non-seizure to seizure. The CTSA tools were applied to four forms of these data: raw EEG data (e-data), artifact data (f-data) via application of a quadratic zero-phase filter of the raw data, artifact-filtered data (g- data) and that was the residual after subtracting f-data from e-data, and a low-pass-filtered version (h-data) of g-data. Two different seizures were analyzed for the same patient. Several nonlinear measures uniquely indicate an epileptic seizure in both cases, including an abrupt decrease in the time per wave cycle in f-data, an abrupt increase in the Kolmogorov entropy and in the correlation dimension for e-h data, and an abrupt increase in the correlation dimension for e-h data. The transition from normal to seizure state also is characterized by distinctly different trends in the nonlinear measures for each seizure and may be potential seizure predictors for this patient. Surrogate analysis of e-data shows that statistically significant nonlinear structure is present during the non-seizure, transition , and seizure epoches.

  17. Expression of Glutamatergic Genes in Healthy Humans across 16 Brain Regions; Altered Expression in the Hippocampus after Chronic Exposure to Alcohol or Cocaine

    PubMed Central

    Enoch, Mary-Anne; Rosser, Alexandra A.; Zhou, Zhifeng; Mash, Deborah C.; Yuan, Qiaoping; Goldman, David

    2014-01-01

    We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from ‘BrainSpan’ was obtained across 16 brain regions from nine control adults. We also generated RNA-Seq data from postmortem hippocampus from eight alcoholics, eight cocaine addicts and eight controls. Expression analyses were undertaken of 28 genes encoding glutamate ionotropic (AMPA, kainate, NMDA) and metabotropic receptor subunits, together with glutamate transporters. The expression of each gene was fairly consistent across the brain with the exception of the cerebellum, the thalamic mediodorsal nucleus and the striatum. GRIN1, encoding the essential NMDA subunit, had the highest expression across all brain regions. Six factors accounted for 84% of the variance in global gene expression. GRIN2B (encoding GluN2B), was up-regulated in both alcoholics and cocaine addicts (FDR corrected p = 0.008). Alcoholics showed up-regulation of three genes relative to controls and cocaine addicts: GRIA4 (encoding GluA4), GRIK3 (GluR7) and GRM4 (mGluR4). Expression of both GRM3 (mGluR3) and GRIN2D (GluN2D) was up-regulated in alcoholics and down-regulated in cocaine addicts relative to controls. Glutamatergic genes are moderately to highly expressed throughout the brain. Six factors explain nearly all the variance in global gene expression. At least in the hippocampus, chronic alcohol use largely up-regulates glutamatergic genes. The NMDA GluN2B receptor subunit might be implicated in a common pathway to addiction, possibly in conjunction with the GABAB1 receptor subunit. PMID:25262781

  18. DFAspike: a new computational proposition for efficient recognition of epileptic spike in EEG.

    PubMed

    Keshri, Anup Kumar; Sinha, Rakesh Kumar; Singh, Aishwarya; Nand Das, Barda

    2011-07-01

    An automated method has been presented for the detection of epileptic spikes in the electroencephalogram (EEG) using a deterministic finite automata (DFA) and has been named as DFAspike. EEG data (sampled, 256 Hz) files are the inputs to the DFAspike. The DFAspike was tested with different data files containing epileptic spikes. The obtained recognition rate of epileptic spike was 99.13% on an average. This system does not require any kind of prior training or human intrusion. The result shows that the designed system can be very effectively used for the detection of spikes present in the recorded EEG signals. PMID:21621200

  19. MiR-181a influences the cognitive function of epileptic rats induced by pentylenetetrazol

    PubMed Central

    Huang, Yiqing; Liu, Xixia; Liao, Yuhan; Luo, Chun; Zou, Donghua; Wei, Xing; Huang, Qi; Wu, Yuan

    2015-01-01

    Our previous study showed that the expression of miR-181a in memory impairment group of pentylenetetrazol (PTZ)-induced epileptic rats was up-regulated, but whether miR-181a influenced the cognitive function of PTZ-induced epileptic rats remains unknown. Therefore, we investigated the role of miR-181a in the cognitive function of PTZ-induced epileptic rats. A model of temporal lobe epilepsy (TLE) was induced via PTZ kindling in SD male rats. The epileptic rats were divided into Epilepsy group, Agomir-control group, miR-181a agomir group, 12 rats for each. 12 rats were used as sham group. We found that compared to the sham group, the expression of miR-181a in the Epilepsy group was increased. We also found that escape latency in the 5th day was prolonged and crossing times in the 6th day was reduced via Morris Water Maze test, which may indicate memory impairment. Furthermore, over-expression of miR-181a effectively reduced Bcl-2 protein level and increased apoptosis in hippocampus. Moreover, compared with Agomir-control group, the escape latency of miR-181a agomir group was obviously induced (P<0.05). Our findings suggest that miR-181a may play a role in impairing the cognitive function of PTZ-induced epileptic rats, and miR-181a could decrease the Bcl-2 protein and induce the apoptosis in the hippocampus that might be the way to impair cognitive function. PMID:26722477

  20. Neuroethological approach to frontolimbic epileptic seizures and parasomnias: The same central pattern generators for the same behaviours.

    PubMed

    Tassinari, C A; Cantalupo, G; Högl, B; Cortelli, P; Tassi, L; Francione, S; Nobili, L; Meletti, S; Rubboli, G; Gardella, E

    2009-10-01

    The aim of this report is not to make a differential diagnosis between epileptic nocturnal seizures and non-epileptic sleep-related movement disorders, or parasomnias. On the contrary, our goal is to emphasize the commonly shared semiological features of some epileptic seizures and parasomnias. Such similar features might be explained by the activation of the same neuronal networks (so-called 'central pattern generators' or CPG). These produce the stereotypical rhythmic motor sequences - in other words, behaviours - that are adaptive and species-specific (such as eating/alimentary, attractive/aversive, locomotor and nesting habits). CPG are located at the subcortical level (mainly in the brain stem and spinal cord) and, in humans, are under the control of the phylogenetically more recent neomammalian neocortical structures, according to a simplified Jacksonian model. Based on video-polygraphic recordings of sleep-related epileptic seizures and non-epileptic events (parasomnias), we have documented how a transient "neomammalian brain" dysfunction - whether epileptic or not - can 'release' (disinhibition?) the CPG responsible for involuntary motor behaviours. Thus, in both epileptic seizures and parasomnias, we can observe: (a) oroalimentary automatisms, bruxism and biting; (b) ambulatory behaviours, ranging from the classical bimanual-bipedal activity of 'frontal' hypermotor seizures, epileptic and non-epileptic wanderings, and somnambulism to periodic leg movements (PLM), alternating leg muscle activation (ALMA) and restless legs syndrome (RLS); and (c) various sleep-related events such as ictal fear, sleep terrors, nightmares and violent behaviour. PMID:19733874

  1. [Drivers license qualification for epileptics].

    PubMed

    Egli, M; Hartmann, H; Hess, R

    1977-03-26

    The question whether a person with epilepsy qualified for a driving licence must be examined from the point of view of the individual as well as that of the community. The general public should be protected against unduly high risks from epileptic drivers, whereas the patient has a right to live as normal a life as possible, which includes driving an automobile. Too rigid criteria for obtaining the license increase the number of persons who evade medical control and drive "illegally". To require physicians to report their epileptic patients to the authorities would be counterproductive; it would also destroy the personal confidence between physician and patient which is so essential for successful treatment. Epileptic persons endanger safety on the road only slightly: 0.1-0.3% of all traffic accidents are due to epileptic seizures. In contrast, abuse of alcohol plays a major role in 6-9% of all accidents, whereas 80-90% are attributable to evident mistakes by the driver. Epileptic patients under regular medical supervision who are licenced on grounds of approved criteria do not cause more accidents than the general population. A dangerous group are, however, those with mental alterations (organic or reactive) and particularly patients with aggressive and expansive-compensatory traits, as well as those driving without permission. Prognostic criteria as to the further course of the disease are paramount for the assessment of qualification for the licence. The following rules have proved their worth: 2 years freedom from seizures (with or without therapy), no abnormalities specific for epilepsy in the EEG, no serious mental changes, regular medical supervision and treatment mus be guaranteed. Departures from these rules should be confined to exceptional cases with the consent of a physician specialized in epileptology. The same holds for admission to higher categories of driving licence, the only practical eventuality being category D (lorries), and even this only in

  2. GABAergic inhibition shapes interictal dynamics in awake epileptic mice.

    PubMed

    Muldoon, Sarah Feldt; Villette, Vincent; Tressard, Thomas; Malvache, Arnaud; Reichinnek, Susanne; Bartolomei, Fabrice; Cossart, Rosa

    2015-10-01

    Epilepsy is characterized by recurrent seizures and brief, synchronous bursts called interictal spikes that are present in-between seizures and observed as transient events in EEG signals. While GABAergic transmission is known to play an important role in shaping healthy brain activity, the role of inhibition in these pathological epileptic dynamics remains unclear. Examining the microcircuits that participate in interictal spikes is thus an important first step towards addressing this issue, as the function of these transient synchronizations in either promoting or prohibiting seizures is currently under debate. To identify the microcircuits recruited in spontaneous interictal spikes in the absence of any proconvulsive drug or anaesthetic agent, we combine a chronic model of epilepsy with in vivo two-photon calcium imaging and multiunit extracellular recordings to map cellular recruitment within large populations of CA1 neurons in mice free to run on a self-paced treadmill. We show that GABAergic neurons, as opposed to their glutamatergic counterparts, are preferentially recruited during spontaneous interictal activity in the CA1 region of the epileptic mouse hippocampus. Although the specific cellular dynamics of interictal spikes are found to be highly variable, they are consistently associated with the activation of GABAergic neurons, resulting in a perisomatic inhibitory restraint that reduces neuronal spiking in the principal cell layer. Given the role of GABAergic neurons in shaping brain activity during normal cognitive function, their aberrant unbalanced recruitment during these transient events could have important downstream effects with clinical implications. PMID:26280596

  3. Ultra-high resolution in-vivo 7.0T structural imaging of the human hippocampus reveals the endfolial pathway.

    PubMed

    Parekh, Mansi B; Rutt, Brian K; Purcell, Ryan; Chen, Yuanxin; Zeineh, Michael M

    2015-05-15

    The hippocampus is a very important structure in memory formation and retrieval, as well as in various neurological disorders such as Alzheimer's disease, epilepsy and depression. It is composed of many intricate subregions making it difficult to study the anatomical changes that take place during disease. The hippocampal hilus may have a unique neuroanatomy in humans compared to that in monkeys and rodents, with field CA3h greatly enlarged in humans compared to that in rodents, and a white-matter pathway, called the endfolial pathway, possibly only present in humans. In this study we have used newly developed 7.0T whole brain imaging sequence, balanced steady-state free precession (bSSFP) that can achieve 0.4mm isotropic images to study, in vivo, the anatomy of the hippocampal hilus. A detailed hippocampal subregional segmentation was performed according to anatomic atlases segmenting the following regions: CA4, CA3, CA2, CA1, SRLM (stratum radiatum lacunosum moleculare), alveus, fornix, and subiculum along with its molecular layer. We also segmented a hypointense structure centrally within the hilus that resembled the endfolial pathway. To validate that this hypointense signal represented the endfolial pathway, we acquired 0.1mm isotropic 8-phase cycle bSSFP on an excised specimen, and then sectioned and stained the specimen for myelin using an anti-myelin basic protein antibody (SMI 94). A structure tensor analysis was calculated on the myelin-stained section to show directionality of the underlying fibers. The endfolial pathway was consistently visualized within the hippocampal body in vivo in all subjects. It is a central pathway in the hippocampus, with unknown relevance in neurodegenerative disorders, but now that it can be visualized noninvasively, we can study its function and alterations in neurodegeneration. PMID:25701699

  4. Using patient-specific hemodynamic response function in epileptic spike analysis of human epilepsy: a study based on EEG-fNIRS.

    PubMed

    Peng, Ke; Nguyen, Dang Khoa; Vannasing, Phetsamone; Tremblay, Julie; Lesage, Frédéric; Pouliot, Philippe

    2016-02-01

    Functional near-infrared spectroscopy (fNIRS) can be combined with electroencephalography (EEG) to continuously monitor the hemodynamic signal evoked by epileptic events such as seizures or interictal epileptiform discharges (IEDs, aka spikes). As estimation methods assuming a canonical shape of the hemodynamic response function (HRF) might not be optimal, we sought to model patient-specific HRF (sHRF) with a simple deconvolution approach for IED-related analysis with EEG-fNIRS data. Furthermore, a quadratic term was added to the model to account for the nonlinearity in the response when IEDs are frequent. Prior to analyzing clinical data, simulations were carried out to show that the HRF was estimable by the proposed deconvolution methods under proper conditions. EEG-fNIRS data of five patients with refractory focal epilepsy were selected due to the presence of frequent clear IEDs and their unambiguous focus localization. For each patient, both the linear sHRF and the nonlinear sHRF were estimated at each channel. Variability of the estimated sHRFs was seen across brain regions and different patients. Compared with the SPM8 canonical HRF (cHRF), including these sHRFs in the general linear model (GLM) analysis led to hemoglobin activations with higher statistical scores as well as larger spatial extents on all five patients. In particular, for patients with frequent IEDs, nonlinear sHRFs were seen to provide higher sensitivity in activation detection than linear sHRFs. These observations support using sHRFs in the analysis of IEDs with EEG-fNIRS data. PMID:26619785

  5. The bumps on the hippocampus

    NASA Astrophysics Data System (ADS)

    Gao, Yi; Ver Hoef, Lawrence

    2016-03-01

    The hippocampus has been the focus of more imaging research than any other subcortical structure in the human brain. However a feature that has been almost universally overlooked are the bumpy ridges on the inferior aspect of the hippocampus, which we refer to as hippocampal dentation. These bumps arise from folds in the CA1 layer of Ammon's horn. Similar to the folding of the cerebral cortex, hippocampal dentation allows for greater surface area in a confined space. However, while quantitative studies of radiologic brain images have been advancing for decades, examining numerous approaches to hippocampal segmentation and morphology analysis, virtually all published 3D renderings of the hippocampus show the under surface to be quite smooth or mildly irregular; we have rarely seen the characteristic bumpy structure in the reconstructed 3D scene, one exception being the 9.4T postmortem study. This is presumably due to the fact that, based on our experience with high resolution images, there is a dramatic degree of variability in hippocampal dentation between individuals from very smooth to highly dentated. An apparent question is, does this indicate that this specific morphological signature can only be captured using expensive ultra-high field techniques? Or, is such information buried in the data we commonly acquire, awaiting a computation technique that can extract and render it clearly? In this study, we propose a super-resolution technique that captures the fine scale morphometric features of the hippocampus based on common T1-weighted 3T MR images.

  6. The hippocampus: a special place for time.

    PubMed

    Ranganath, Charan; Hsieh, Liang-Tien

    2016-04-01

    Many findings have demonstrated that memories of past events are temporally organized. It is well known that the hippocampus is critical for such episodic memories, but, until recently, little was known about the temporal organization of mnemonic representations in the hippocampus. Recent developments in human and animal research have revealed important insights into the role of the hippocampus in learning and retrieving sequences of events. Here, we review these findings, including lesion and single-unit recording studies in rodents, functional magnetic resonance imaging studies in humans, and computational models that link findings from these studies to the anatomy of the hippocampal circuit. The findings converge toward the idea that the hippocampus is essential for learning sequences of events, allowing the brain to distinguish between memories for conceptually similar but temporally distinct episodes, and to associate representations of temporally contiguous, but otherwise unrelated experiences. PMID:27082833

  7. In silico prioritization based on coexpression can aid epileptic encephalopathy gene discovery

    PubMed Central

    Oliver, Karen L.; Lukic, Vesna; Freytag, Saskia; Scheffer, Ingrid E.; Berkovic, Samuel F.

    2016-01-01

    Objective: To evaluate the performance of an in silico prioritization approach that was applied to 179 epileptic encephalopathy candidate genes in 2013 and to expand the application of this approach to the whole genome based on expression data from the Allen Human Brain Atlas. Methods: PubMed searches determined which of the 179 epileptic encephalopathy candidate genes had been validated. For validated genes, it was noted whether they were 1 of the 19 of 179 candidates prioritized in 2013. The in silico prioritization approach was applied genome-wide; all genes were ranked according to their coexpression strength with a reference set (i.e., 51 established epileptic encephalopathy genes) in both adult and developing human brain expression data sets. Candidate genes ranked in the top 10% for both data sets were cross-referenced with genes previously implicated in the epileptic encephalopathies due to a de novo variant. Results: Five of 6 validated epileptic encephalopathy candidate genes were among the 19 prioritized in 2013 (odds ratio = 54, 95% confidence interval [7,∞], p = 4.5 × 10−5, Fisher exact test); one gene was false negative. A total of 297 genes ranked in the top 10% for both the adult and developing brain data sets based on coexpression with the reference set. Of these, 9 had been previously implicated in the epileptic encephalopathies (FBXO41, PLXNA1, ACOT4, PAK6, GABBR2, YWHAG, NBEA, KNDC1, and SELRC1). Conclusions: We conclude that brain gene coexpression data can be used to assist epileptic encephalopathy gene discovery and propose 9 genes as strong epileptic encephalopathy candidates worthy of further investigation. PMID:27066588

  8. Neurotransmission in the hippocampus

    SciTech Connect

    Frotscher, D. ); Kugler, P. ); Misgled, U. ); Zilles, K. (Anatomisches Institut der Universitat Koln, Joseph-Stelzmann-S

    1988-01-01

    This book contains the following five chapters: introduction; neuronal elements in the hippocampus and their synaptic connections; Membrane properties and postsynaptic responses of hippocampal neurons; The enzyme histochemistry of neurotransmitter metabolism; and Receptor autoradiography in the hippocampus of man and rat.

  9. Metabolic Causes of Epileptic Encephalopathy

    PubMed Central

    Pearl, Phillip L.

    2013-01-01

    Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if untreated can often be catastrophic. The importance of early recognition cannot be overemphasized. This paper provides an overview of inborn metabolic errors associated with persistent brain disturbances due to highly active clinical or electrographic ictal activity. Selected diseases are organized by the defective molecule or mechanism and categorized as small molecule disorders (involving amino and organic acids, fatty acids, neurotransmitters, urea cycle, vitamers and cofactors, and mitochondria) and large molecule disorders (including lysosomal storage disorders, peroxisomal disorders, glycosylation disorders, and leukodystrophies). Details including key clinical features, salient electrophysiological and neuroradiological findings, biochemical findings, and treatment options are summarized for prominent disorders in each category. PMID:23762547

  10. Acquired equivalence associative learning in GTC epileptic patients: experimental and computational study

    PubMed Central

    Khalil, Radwa; Abo Elfetoh, Noha; Moftah, Marie Z.; Khedr, Eman M.

    2015-01-01

    Previous cognitive behavioral studies based on Acquired Equivalence Associative learning Task (AEALT) showed a strong relation between hippocampus and basal ganglia in associative learning. However, experimental behavioral studies of patients with Generalized Tonic Clonic (GTC) epilepsy remained sparse. The aim of the present study is to integrate a classical behavioral cognitive analysis with a computational model approach to investigate cognitive associative learning impairments in patients with GTC epilepsy. We measured the accuracy of associative learning response performance in five GTC epileptic patients and five control subjects by using AEALT, all subjects were matched in age and gender. We ran the task using E-Prime, a neuropsychological software program, and SPSS for data statistical analysis. We tested whether GTC epileptic patients would have different learning performance than normal subjects, based on the degree and the location of impairment either in basal ganglia and/or hippocampus. With the number of patients that was available, our behavioral analysis showed no remarkable differences in learning performance of GTC patients as compared to their control subjects, both in the transfer and acquisition phases. In parallel, our simulation results confirmed strong connection and interaction between hippocampus and basal ganglia in our GTC and their control subjects. Nevertheless, the differences in neural firing rate of the connectionist model and weight update of basal ganglia were not significantly different between GTC and control subjects. Therefore, the behavioral analysis and the simulation data provided the same result, thus indicating that the computational model is likely to predict cognitive outcomes. PMID:26578883

  11. Tracking inflammation in the epileptic rat brain by bi-functional fluorescent and magnetic nanoparticles.

    PubMed

    Portnoy, Emma; Polyak, Boris; Inbar, Dorrit; Kenan, Gilad; Rai, Ahmad; Wehrli, Suzanne L; Roberts, Timothy P L; Bishara, Ameer; Mann, Aniv; Shmuel, Miriam; Rozovsky, Katya; Itzhak, Gal; Ben-Hur, Tamir; Magdassi, Shlomo; Ekstein, Dana; Eyal, Sara

    2016-07-01

    Correct localization of epileptic foci can improve surgical outcome in patients with drug-resistant seizures. Our aim was to demonstrate that systemically injected nanoparticles identify activated immune cells, which have been reported to accumulate in epileptogenic brain tissue. Fluorescent and magnetite-labeled nanoparticles were injected intravenously to rats with lithium-pilocarpine-induced chronic epilepsy. Cerebral uptake was studied ex vivo by confocal microscopy and MRI. Cellular uptake and biological effects were characterized in vitro in murine monocytes and microglia cell lines. Microscopy confirmed that the nanoparticles selectively accumulate within myeloid cells in the hippocampus, in association with inflammation. The nanoparticle signal was also detectable by MRI. The in vitro studies demonstrate rapid nanoparticle uptake and good cellular tolerability. We show that nanoparticles can target myeloid cells in epileptogenic brain tissue. This system can contribute to pre-surgical and intra-surgical localization of epileptic foci, and assist in detecting immune system involvement in epilepsy. PMID:26964483

  12. Current understanding and neurobiology of epileptic encephalopathies.

    PubMed

    Auvin, Stéphane; Cilio, Maria Roberta; Vezzani, Annamaria

    2016-08-01

    Epileptic encephalopathies are a group of diseases in which epileptic activity itself contributes to severe cognitive and behavioral impairments above and beyond what might be expected from the underlying pathology alone. These impairments can worsen over time. This concept has been continually redefined since its introduction. A few syndromes are considered epileptic encephalopathies: early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, epilepsy of infancy with migrating focal seizures, West syndrome or infantile spasms, Dravet syndrome during infancy, Lennox-Gastaut syndrome, epileptic encephalopathy with continuous spikes-and-waves during sleep, and Landau-Kleffner syndrome during childhood. The inappropriate use of this term to refer to all severe epilepsy syndromes with intractable seizures and severe cognitive dysfunction has led to confusion regarding the concept of epileptic encephalopathy. Here, we review our current understanding of those epilepsy syndromes considered to be epileptic encephalopathies. Genetic studies have provided a better knowledge of neonatal and infantile epilepsy syndromes, while neuroimaging studies have shed light on the underlying causes of childhood-onset epileptic encephalopathies such as Lennox-Gastaut syndrome. Apart from infantile spasm models, we lack animal models to explain the neurobiological mechanisms at work in these conditions. Experimental studies suggest that neuroinflammation may be a common neurobiological pathway that contributes to seizure refractoriness and cognitive involvement in the developing brain. PMID:26992889

  13. Post-epileptic headache and migraine.

    PubMed Central

    Schon, F; Blau, J N

    1987-01-01

    One hundred epileptic patients were questioned about their headaches. Post-ictal headaches occurred in 51 of these patients and most commonly lasted 6-72 hours. Major seizures were more often associated with post-epileptic headaches than minor attacks. Nine patients in this series of 100 also had migraine: in eight of these nine a typical, albeit a mild, migraine attack was provoked by fits. The post-ictal headache in the 40 epileptics who did not have migraine was accompanied by vomiting in 11 cases, photophobia in 14 cases and vomiting with photophobia in 4 cases. Furthermore, post-epileptic headache was accentuated by coughing, bending and sudden head movements and relieved by sleep. It is, therefore, clear that seizures provoke a syndrome similar to the headache phase of migraine in 50% of epileptics. It is proposed that post-epileptic headache arises intracranially and is related to the vasodilatation known to follow seizures. The relationship of post-epileptic headache to migraine is discussed in the light of current ideas on migraine pathogenesis, in particular the vasodilation which accompanies Leao's spreading cortical depression. PMID:3117978

  14. Ambroxol-induced focal epileptic seizure.

    PubMed

    Lapenta, Leonardo; Morano, Alessandra; Fattouch, Jinane; Casciato, Sara; Fanella, Martina; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

    2014-01-01

    It is well known that in epileptic patients some compounds and different drugs used for the treatment of comorbidities can facilitate or provoke seizures, this evidence regarding a wide spectrum of pharmacological categories. The potential facilitating factors usually include direct toxic effects or pharmacological interactions of either active ingredients or excipients. We report the case of a patient with drug-resistant epilepsy who experienced focal epileptic seizures, easily and constantly reproducible, after each administration of a cough syrup. This is, to our knowledge, the first electroencephalogram-documented case of focal epileptic seizures induced by cough syrup containing ambroxol as active ingredient. PMID:24824664

  15. Newer anti-epileptic drugs.

    PubMed

    Aneja, S; Newton, R W

    1996-01-01

    During the past few years, a number of drugs have been added to the anti-epileptic arsenal. This review focusses on five of these drugs which have undergone extensive trials: Vigabatrin, Lamotrigine, Gabapentin, Felbamate and Oxcarbazepine. Some of these antiepileptic drugs appear to be helpful for treatment of catastrophic childhood epilepsies. Vigabatrin appears promising in children with infantile spasms who do not respond to ACTH or Prednisolone. Children with Lennox-Gastaut syndrome may respond to treatment with Lamotrigine or Vigabatrin. Gabapentin and vigabatrin have proved to be effective in refractory partial seizures. Oxcarbazepine, a ketoderivative of carbamazepine, is as effective as Carbamazepine but has a better safety profile. Lesser neurotoxicity and fewer drug interactions is another advantage with these drugs. However monitoring is required to determine the long term safety with their usage. These drugs have a definite role in childhood epilepsies refractory to conventional antiepileptic drugs. PMID:10829995

  16. Epileptic spike recognition in electroencephalogram using deterministic finite automata.

    PubMed

    Keshri, Anup Kumar; Sinha, Rakesh Kumar; Hatwal, Rajesh; Das, Barda Nand

    2009-06-01

    This Paper presents an automated method of Epileptic Spike detection in Electroencephalogram (EEG) using Deterministic Finite Automata (DFA). It takes prerecorded single channel EEG data file as input and finds the occurrences of Epileptic Spikes data in it. The EEG signal was recorded at 256 Hz in two minutes separate data files using the Visual Lab-M software (ADLink Technology Inc., Taiwan). It was preprocessed for removal of baseline shift and band pass filtered using an infinite impulse response (IIR) Butterworth filter. A system, whose functionality was modeled with DFA, was designed. The system was tested with 10 EEG signal data files. The recognition rate of Epileptic Spike as on average was 95.68%. This system does not require any human intrusion. Also it does not need any short of training. The result shows that the application of DFA can be useful in detection of different characteristics present in EEG signals. This approach could be extended to a continuous data processing system. PMID:19408450

  17. Clinical review of genetic epileptic encephalopathies

    PubMed Central

    Noh, Grace J.; Asher, Y. Jane Tavyev; Graham, John M.

    2012-01-01

    Seizures are a frequently encountered finding in patients seen for clinical genetics evaluations. The differential diagnosis for the cause of seizures is quite diverse and complex, and more than half of all epilepsies have been attributed to a genetic cause. Given the complexity of such evaluations, we highlight the more common causes of genetic epileptic encephalopathies and emphasize the usefulness of recent technological advances. The purpose of this review is to serve as a practical guide for clinical geneticists in the evaluation and counseling of patients with genetic epileptic encephalopathies. Common syndromes will be discussed, in addition to specific seizure phenotypes, many of which are refractory to anti-epileptic agents. Divided by etiology, we overview the more common causes of infantile epileptic encephalopathies, channelopathies, syndromic, metabolic, and chromosomal entities. For each condition, we will outline the diagnostic evaluation and discuss effective treatment strategies that should be considered. PMID:22342633

  18. Chewing Maintains Hippocampus-Dependent Cognitive Function

    PubMed Central

    Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2015-01-01

    Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research. PMID:26078711

  19. Mesial temporal lobe epilepsy lateralization using SPHARM-based features of hippocampus and SVM

    NASA Astrophysics Data System (ADS)

    Esmaeilzadeh, Mohammad; Soltanian-Zadeh, Hamid; Jafari-Khouzani, Kourosh

    2012-02-01

    This paper improves the Lateralization (identification of the epileptogenic hippocampus) accuracy in Mesial Temporal Lobe Epilepsy (mTLE). In patients with this kind of epilepsy, usually one of the brain's hippocampi is the focus of the epileptic seizures, and resection of the seizure focus is the ultimate treatment to control or reduce the seizures. Moreover, the epileptogenic hippocampus is prone to shrinkage and deformation; therefore, shape analysis of the hippocampus is advantageous in the preoperative assessment for the Lateralization. The method utilized for shape analysis is the Spherical Harmonics (SPHARM). In this method, the shape of interest is decomposed using a set of bases functions and the obtained coefficients of expansion are the features describing the shape. To perform shape comparison and analysis, some pre- and post-processing steps such as "alignment of different subjects' hippocampi" and the "reduction of feature-space dimension" are required. To this end, first order ellipsoid is used for alignment. For dimension reduction, we propose to keep only the SPHARM coefficients with maximum conformity to the hippocampus shape. Then, using these coefficients of normal and epileptic subjects along with 3D invariants, specific lateralization indices are proposed. Consequently, the 1536 SPHARM coefficients of each subject are summarized into 3 indices, where for each index the negative (positive) value shows that the left (right) hippocampus is deformed (diseased). Employing these indices, the best achieved lateralization accuracy for clustering and classification algorithms are 85% and 92%, respectively. This is a significant improvement compared to the conventional volumetric method.

  20. Epileptic encephalopathies: new genes and new pathways.

    PubMed

    Nieh, Sahar Esmaeeli; Sherr, Elliott H

    2014-10-01

    Epileptic encephalopathies represent a group of devastating epileptic disorders that occur early in life and are often characterized by pharmaco-resistant epilepsy, persistent severe electroencephalographic abnormalities, and cognitive dysfunction or decline. Next generation sequencing technologies have increased the speed of gene discovery tremendously. Whereas ion channel genes were long considered to be the only significant group of genes implicated in the genetic epilepsies, a growing number of non-ion-channel genes are now being identified. As a subgroup of the genetically mediated epilepsies, epileptic encephalopathies are complex and heterogeneous disorders, making diagnosis and treatment decisions difficult. Recent exome sequencing data suggest that mutations causing epileptic encephalopathies are often sporadic, typically resulting from de novo dominant mutations in a single autosomal gene, although inherited autosomal recessive and X-linked forms also exist. In this review we provide a summary of the key features of several early- and mid-childhood onset epileptic encephalopathies including Ohtahara syndrome, Dravet syndrome, Infantile spasms and Lennox Gastaut syndrome. We review the recent next generation sequencing findings that may impact treatment choices. We also describe the use of conventional and newer anti-epileptic and hormonal medications in the various syndromes based on their genetic profile. At a biological level, developments in cellular reprogramming and genome editing represent a new direction in modeling these pediatric epilepsies and could be used in the development of novel and repurposed therapies. PMID:25266964

  1. Epileptogenesis and epileptic maturation in phosphorylation site-specific SNAP-25 mutant mice.

    PubMed

    Watanabe, Shigeru; Yamamori, Saori; Otsuka, Shintaro; Saito, Masanori; Suzuki, Eiji; Kataoka, Masakazu; Miyaoka, Hitoshi; Takahashi, Masami

    2015-09-01

    Snap25(S187A/S187A) mouse is a knock-in mouse with a single amino acid substitution at a protein kinase C-dependent phosphorylation site of the synaptosomal-associated protein of 25 kDa (SNAP-25), which is a target-soluble NSF attachment protein receptor (t-SNARE) protein essential for neurotransmitter release. Snap25(S187A/S187A) mice exhibit several distinct phenotypes, including reductions in dopamine and serotonin release in the brain, anxiety-like behavior, and cognitive dysfunctions. Homozygous mice show spontaneous epileptic convulsions, and about 15% of the mice die around three weeks after birth. The remaining mice survive for almost two years and exhibit spontaneous recurrent seizures throughout their lifetime. Here, we conducted long-term continuous video electroencephalogram recording of the mice and analyzed the process of epileptogenesis and epileptic maturation in detail. Spikes and slow-wave discharges (SWDs) were observed in the cerebral cortex and thalamus before epileptic convulsions began. SWDs showed several properties similar to those observed in absence seizures including (1) lack of in the hippocampus, (2) movement arrest during SWDs, and (3) inhibition by ethosuximide. Multiple generalized seizures occurred in all homozygous mice around three weeks after birth. However, seizure generation stopped within several days, and a seizure-free latent period began. Following a spike-free quiet period, the number of spikes increased gradually, and epileptic seizures reappeared. Subsequently, spontaneous seizures occurred cyclically throughout the life of the mice, and several progressive changes in seizure frequency, seizure duration, seizure cycle interval, seizure waveform, and the number and waveform of epileptic discharges during slow-wave sleep occurred with different time courses over 10 weeks. Anxiety-related behaviors appeared suddenly within three days after epileptic seizures began and were delayed markedly by oral administration of

  2. Downregulation of gephyrin in temporal lobe epilepsy neurons in humans and a rat model.

    PubMed

    Fang, Min; Shen, Lan; Yin, Huan; Pan, Yu-Min; Wang, Liang; Chen, Dan; Xi, Zhi-Qin; Xiao, Zheng; Wang, Xue-Feng; Zhou, Sheng-Nian

    2011-10-01

    Gephyrin, which is a postsynaptic scaffolding protein participated in clustering GABA(A) receptors at inhibitory synapses, has been reported to be involved in temporal lobe epilepsy (TLE) recently. Here, we investigate gephyrin protein expression in the temporal lobe epileptic foci in epileptic patients and experimental animals in order to explore the probable relationship between gephyrin expression and TLE. Using immunohistochemistry, immunofluorescence, and western blot analysis, gephyrin expression was examined in 30 human temporal neocortex samples from patients who underwent surgery to treat drug-refractory TLE and 10 histological normal temporal neocortex from the controls. Meanwhile, we investigated the gephyrin expression in the hippocampus and adjacent neocortex from experimental rats on 24 h, 48 h, 1 week, 2 weeks, 1 month, and 2 months postseizure and from control rats. Gephyrin protein was mainly expressed in the membrane and cytoplasm of neurons in temporal lobe epileptic foci in humans and experimental rats. Gephyrin expression was significantly lower in the temporal neocortex of TLE patients compared to the controls. In experimental rats, the expression of gephyrin in temporal lobe was downregulated in epileptic groups compared to the control group. Gephyrin expression gradually decreased during the acute period and the latent period, but then began to increase below the levels seen in controls during the chronic phase. Our findings suggest that gephyrin may be involved in the development of TLE. PMID:21404332

  3. Music and its association with epileptic disorders.

    PubMed

    Maguire, Melissa

    2015-01-01

    The association between music and epileptic seizures is complex and intriguing. Musical processing within the human brain recruits a network which involves many cortical areas that could activate as part of a temporal lobe seizure or become hyperexcitable on musical exposure as in the case of musicogenic epilepsy. The dichotomous effect of music on seizures may be explained by modification of dopaminergic circuitry or counteractive cognitive and sensory input in ictogenesis. Research has explored the utility of music as a therapy in epilepsy and while limited studies show some evidence of an effect on seizure activity; further work is required to ascertain its clinical potential. Sodium channel-blocking antiepileptic drugs, e.g., carbamazepine and oxcarbazepine, appear to effect pitch perception particularly in native-born Japanese, a rare but important adverse effect, particularly if a professional musician. Temporal lobe surgery for right lateralizing epilepsy has the capacity to effect all facets of musical processing, although risk and correlation to resection area need further research. There is a need for the development of investigative tools of musical processing that could be utilized along the surgical pathway. Similarly, work is also required in devising a musical paradigm as part of electroencephalography to improve surveillance of musicogenic seizures. These clinical applications could aid the management of epilepsy and preservation of musical ability. PMID:25725912

  4. Naringin Attenuates Autophagic Stress and Neuroinflammation in Kainic Acid-Treated Hippocampus In Vivo.

    PubMed

    Jeong, Kyoung Hoon; Jung, Un Ju; Kim, Sang Ryong

    2015-01-01

    Kainic acid (KA) is well known as a chemical compound to study epileptic seizures and neuronal excitotoxicity. KA-induced excitotoxicity causes neuronal death by induction of autophagic stress and microglia-derived neuroinflammation, suggesting that the control of KA-induced effects may be important to inhibit epileptic seizures with neuroprotection. Naringin, a flavonoid in grapefruit and citrus fruits, has anti-inflammatory and antioxidative activities, resulting in neuroprotection in animal models from neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. In the present study, we examined its beneficial effects involved in antiautophagic stress and antineuroinflammation in the KA-treated hippocampus. Our results showed that naringin treatment delayed the onset of KA-induced seizures and decreased the occurrence of chronic spontaneous recurrent seizures (SRS) in KA-treated mice. Moreover, naringin treatment protected hippocampal CA1 neurons in the KA-treated hippocampus, ameliorated KA-induced autophagic stress, confirmed by the expression of microtubule-associated protein light chain 3 (LC3), and attenuated an increase in tumor necrosis factor-α (TNFα) in activated microglia. These results suggest that naringin may have beneficial effects of preventing epileptic events and neuronal death through antiautophagic stress and antineuroinflammation in the hippocampus in vivo. PMID:26124853

  5. Cell Signaling Underlying Epileptic Behavior

    PubMed Central

    Bozzi, Yuri; Dunleavy, Mark; Henshall, David C.

    2011-01-01

    Epilepsy is a complex disease, characterized by the repeated occurrence of bursts of electrical activity (seizures) in specific brain areas. The behavioral outcome of seizure events strongly depends on the brain regions that are affected by overactivity. Here we review the intracellular signaling pathways involved in the generation of seizures in epileptogenic areas. Pathways activated by modulatory neurotransmitters (dopamine, norepinephrine, and serotonin), involving the activation of extracellular-regulated kinases and the induction of immediate early genes (IEGs) will be first discussed in relation to the occurrence of acute seizure events. Activation of IEGs has been proposed to lead to long-term molecular and behavioral responses induced by acute seizures. We also review deleterious consequences of seizure activity, focusing on the contribution of apoptosis-associated signaling pathways to the progression of the disease. A deep understanding of signaling pathways involved in both acute- and long-term responses to seizures continues to be crucial to unravel the origins of epileptic behaviors and ultimately identify novel therapeutic targets for the cure of epilepsy. PMID:21852968

  6. Pattern Separation Deficits Following Damage to the Hippocampus

    ERIC Educational Resources Information Center

    Kirwan, C. Brock; Hartshorn, Andrew; Stark, Shauna M.; Goodrich-Hunsaker, Naomi J.; Hopkins, Ramona O.; Stark, Craig E. L.

    2012-01-01

    Computational models of hippocampal function propose that the hippocampus is capable of rapidly storing distinct representations through a process known as pattern separation. This prediction is supported by electrophysiological data from rodents and neuroimaging data from humans. Here, we test the prediction that damage to the hippocampus would…

  7. Role of the Dorsal Hippocampus in Object Memory Load

    ERIC Educational Resources Information Center

    Sannino, Sara; Russo, Fabio; Torromino, Giulia; Pendolino, Valentina; Calabresi, Paolo; De Leonibus, Elvira

    2012-01-01

    The dorsal hippocampus is crucial for mammalian spatial memory, but its exact role in item memory is still hotly debated. Recent evidence in humans suggested that the hippocampus might be selectively involved in item short-term memory to deal with an increasing memory load. In this study, we sought to test this hypothesis. To this aim we developed…

  8. Predicting Epileptic Seizures in Advance

    PubMed Central

    Moghim, Negin; Corne, David W.

    2014-01-01

    Epilepsy is the second most common neurological disorder, affecting 0.6–0.8% of the world's population. In this neurological disorder, abnormal activity of the brain causes seizures, the nature of which tend to be sudden. Antiepileptic Drugs (AEDs) are used as long-term therapeutic solutions that control the condition. Of those treated with AEDs, 35% become resistant to medication. The unpredictable nature of seizures poses risks for the individual with epilepsy. It is clearly desirable to find more effective ways of preventing seizures for such patients. The automatic detection of oncoming seizures, before their actual onset, can facilitate timely intervention and hence minimize these risks. In addition, advance prediction of seizures can enrich our understanding of the epileptic brain. In this study, drawing on the body of work behind automatic seizure detection and prediction from digitised Invasive Electroencephalography (EEG) data, a prediction algorithm, ASPPR (Advance Seizure Prediction via Pre-ictal Relabeling), is described. ASPPR facilitates the learning of predictive models targeted at recognizing patterns in EEG activity that are in a specific time window in advance of a seizure. It then exploits advanced machine learning coupled with the design and selection of appropriate features from EEG signals. Results, from evaluating ASPPR independently on 21 different patients, suggest that seizures for many patients can be predicted up to 20 minutes in advance of their onset. Compared to benchmark performance represented by a mean S1-Score (harmonic mean of Sensitivity and Specificity) of 90.6% for predicting seizure onset between 0 and 5 minutes in advance, ASPPR achieves mean S1-Scores of: 96.30% for prediction between 1 and 6 minutes in advance, 96.13% for prediction between 8 and 13 minutes in advance, 94.5% for prediction between 14 and 19 minutes in advance, and 94.2% for prediction between 20 and 25 minutes in advance. PMID:24911316

  9. Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease.

    PubMed

    Zeineh, Michael M; Chen, Yuanxin; Kitzler, Hagen H; Hammond, Robert; Vogel, Hannes; Rutt, Brian K

    2015-09-01

    Although amyloid plaques and neurofibrillary pathology play important roles in Alzheimer disease (AD), our understanding of AD is incomplete, and the contribution of microglia and iron to neurodegeneration is unknown. High-field magnetic resonance imaging (MRI) is exquisitely sensitive to microscopic iron. To explore iron-associated neuroinflammatory AD pathology, we studied AD and control human brain specimens by (1) performing ultra-high resolution ex vivo 7 Tesla MRI, (2) coregistering the MRI with successive histologic staining for iron, microglia, amyloid beta, and tau, and (3) quantifying the relationship between magnetic resonance signal intensity and histological staining. In AD, we identified numerous small MR hypointensities primarily within the subiculum that were best explained by the combination of microscopic iron and activated microglia (p = 0.025), in contradistinction to the relatively lesser contribution of tau or amyloid. Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI. PMID:26190634

  10. Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease

    PubMed Central

    Zeineh, Michael M.; Chen, Yuanxin; Kitzler, Hagen H.; Hammond, Robert; Vogel, Hannes; Rutt, Brian K.

    2016-01-01

    Although amyloid plaques and neurofibrillary pathology play important roles in Alzheimer disease (AD), our understanding of AD is incomplete, and the contribution of microglia and iron to neurodegeneration is unknown. High-field magnetic resonance imaging (MRI) is exquisitely sensitive to microscopic iron. To explore iron-associated neuroinflammatory AD pathology, we studied AD and control human brain specimens by (1) performing ultra-high resolution ex vivo 7 Tesla MRI, (2) coregistering the MRI with successive histologic staining for iron, microglia, amyloid beta, and tau, and (3) quantifying the relationship between magnetic resonance signal intensity and histological staining. In AD, we identified numerous small MR hypointensities primarily within the subiculum that were best explained by the combination of microscopic iron and activated microglia (p = 0.025), in contradistinction to the relatively lesser contribution of tau or amyloid. Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI. PMID:26190634

  11. Pediatric Epileptic Encephalopathies: Pathophysiology and Animal Models.

    PubMed

    Shao, Li-Rong; Stafstrom, Carl E

    2016-05-01

    Epileptic encephalopathies are syndromes in which seizures or interictal epileptiform activity contribute to or exacerbate brain function, beyond that caused by the underlying pathology. These severe epilepsies begin early in life, are associated with poor lifelong outcome, and are resistant to most treatments. Therefore, they represent an immense challenge for families and the medical care system. Furthermore, the pathogenic mechanisms underlying the epileptic encephalopathies are poorly understood, hampering attempts to devise novel treatments. This article reviews animal models of the three classic epileptic encephalopathies-West syndrome (infantile spasms), Lennox-Gastaut syndrome, and continuous spike waves during sleep or Landau-Kleffner syndrome-with discussion of how animal models are revealing underlying pathophysiological mechanisms that might be amenable to targeted therapy. PMID:27544466

  12. Sleep in epileptic beagles and antiepileptics.

    PubMed

    Wauquier, A; Van den Broeck, W A; Edmonds, H L

    1986-01-01

    The sleep-wakefulness (S-W) patterns in 4 genetically epileptic beagles were studied. As compared to normal beagles, there was no change in the percentage time spent in the different stages of S-W. However, epileptic dogs tended towards more and shorter S-W epochs and they had a statistically significant shortening of both REM and deep slow wave sleep (dSWS) latency. The antiepileptics diazepam, phenytoin, flunarizine and phenobarbital did not yield marked effects on S-W patterns, but the REM and dSWS latencies were affected. It is suggested that epileptic beagles may be useful in experimental analysis of epilepsy as well as in drug development. PMID:3609846

  13. "Anything is good that stimulates thought" in the hippocampus. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

    NASA Astrophysics Data System (ADS)

    Hofmann, Markus J.; Kuchinke, Lars

    2015-06-01

    While the emotional trias of brainstem, diencephalon, and orbitofrontal cortex is generally accepted to hold an affective function at its core, fewer researchers would agree that the least common denominator function of the hippocampus is affective [1]. There is a greater consensus on complementary learning systems theory proposing that in contrast to the outer cerebral cortex hosting more stable memories, synaptic associations in the hippocampus create novel knowledge in the context of episodic memories [2]. We chose Oscar Wilde's quote [3, p. 108] as title because we think that the novel hippocampal conjunction of for the most part familiar (long-term) knowledge patterns elicits the positive affect of appreciation [4,5].

  14. Sudden unexpected death in epileptics following sudden, intense, increases in geomagnetic activity: Prevalence of effect and potential mechanisms

    NASA Astrophysics Data System (ADS)

    Persinger, M. A.; Psych, C.

    1995-12-01

    Abrupt, intense increases in global geomagnetic activity during the local night may precipitate a significant proportion of sudden unexpected (or unexplained) deaths (SUD) in epileptics. Over a 2-year period SUD in healthy chronic epileptic rats occurred when the average daily geomagnetic activity exceeded 50 nT (nanoTesla) and suddenly began during local night. Other experiments demonstrated that epileptic rats displayed more spontaneous seizures per night if there had been sudden increases in geomagnetic activity. Analyses of previously published data indicated that the number of SUDs/month in a population of human epileptics was positively associated with the number of days/month when the average geomagnetic activity exceeded 50 nT. The results support the hypothesis that suppression of the nocturnal concentrations of the endogenous anticonvulsant melatonin by sudden increases in geomagnetic activity may encourage fatal cardiac arrhythmias by uncoupling the insular/amygdaloid-paraventricular hypothalamic-solitary nucleus pathways.

  15. Psychogenic non-epileptic seizures (PNES).

    PubMed

    Hingray, C; Biberon, J; El-Hage, W; de Toffol, B

    2016-01-01

    Psychogenic non-epileptic seizures (PNES) are defined as change in behavior or consciousness resembling epileptic seizures but which have a psychological origin. PNES are categorized as a manifestation of dissociative or somatoform (conversion) disorders. Video-EEG recording of an event is the gold standard for diagnosis. PNES represent a symptom, not the underlying disease and the mechanism of dissociation is pivotal in the pathophysiology. Predisposing, precipitating and perpetuating factors should be carefully assessed on a case-by-case basis. The process of communicating the diagnosis using a multidisciplinary approach is an important and effective therapeutic step. PMID:27117433

  16. [Psychodynamic aspects of the epileptic experience].

    PubMed

    Mazza, S; Azzoni, A

    1989-01-01

    The authors deal with the problem of epileptic manifestations from a psychodynamic point of view. The complex aspects of "mind-body" relationship are pointed out. Starting from Freud's theory, several interpretations of the epileptic experience are reviewed. A special attention is drawn to Bion's theory of "protomental apparatus". The authors conclude that it is possible to integrate neuro-physiologic data with psychic aspects of the phenomenon, through a search of its roots in the early phases of Self-setting. PMID:2467374

  17. From superstitious behavior to delusional thinking: the role of the hippocampus in misattributions of causality.

    PubMed

    Brugger, P; Dowdy, M A; Graves, R E

    1994-12-01

    Nearly half a century ago B. F. Skinner proposed the hypothesis that human superstitiousness would be equivalent to the 'superstitious' behavior displayed by animals in operant situations involving response-independent reinforcement. Surprisingly, no attempt has ever been made to test this equivalence hypothesis experimentally. In the light of recent evidence for a common neurological basis of both superstitious beliefs held by normal subjects and delusional ideas of psychotic patients, Skinner's hypothesis has become topical again. We present an extension of the hypothesis which assumes dysfunction of the medial temporal lobe, in particular of the hippocampus, to be responsible for conditioned superstitions in animals, for common everyday superstitions, and for schizophrenic delusions. This hypothesis is based on (1) the observation of an enhanced 'superstitious' reactivity in hippocampectomized animals, (2) findings of an increased occurrence of popular superstitions in patients with a temporal-limbic epileptic focus, and (3) morphological and pharmacological evidence for schizophrenic delusions to be causally related to hippocampal damage. PMID:7739412

  18. Modulation of axonal sprouting along rostro-caudal axis of dorsal hippocampus and no neuronal survival in parahippocampal cortices by long-term post-lesion melatonin administration in lithium-pilocarpine model of temporal lobe epilepsy

    PubMed Central

    Ganjkhani, Mahin; Ali, Rostami; Iraj, Jafari Anarkooli

    2016-01-01

    Feature outcome of hippocampus and extra-hippocampal cortices was evaluated in melatonin treated lithium-pilocarpine epileptic rats during early and chronic phases of temporal lobe epilepsy (TLE). After status epilepticus (SE) induction, 5 and 20 mg/kg melatonin were administered for 14 days or 60 days. All animals were killed 60 days post SE induction and the histological features of the rosrto-caudal axis of the dorsal hippocampus, piriform and entorhinal cortices were evaluated utilizing Nissl, Timm, and synapsin I immunoflorescent staining. Melatonin (20 mg/kg) effect on CA1 and CA3 neurons showed a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. The number of counted granular cells by melatonin (20 mg/kg) treatment increased along the rostro-caudal axis of the dorsal hippocampus in comparison to the untreated epileptic group. The density of Timm granules in the inner molecular layer of the dentate gyrus decreased significantly in all melatonin treated groups in comparison to the untreated epileptic animals. The increased density of synapsin I immunoreactivity in the outer molecular layer of the dentate gyrus of untreated epileptic rats showed a profound decrease following melatonin treatment. There was no neuronal protection in the piriform and entorhinal cortices whatever the melatonin treatment. Long-term melatonin administration as a co-adjuvant probably could reduce the post-lesion histological consequences of TLE in a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. PMID:27051565

  19. [Civil and criminal responsibility of epileptics].

    PubMed

    Villanueva, F

    1997-03-01

    Since the new Penal Code has come into force, certain sections have been altered, such as those dealing with exculpatory circumstances, and as specialists treating patients with possible mental changes, we should be aware that section 20 now takes the place of the former section 8. The situation of the epileptic with regard to civil and criminal responsibility, has hardly changed. This is not surprising in view of current clinico-therapeutic knowledge. Epileptic patients are legally able to testify, inherit etc. and also have the obligation to compensate for damage they have caused. An attempt is made to define the immunity from prosecution of epileptics in accordance with non-static criteria, and to use a mixed biological-mental formula, which would make it possible to discover whether there was an alteration or anomaly of mental state at the time of the criminal offence, which would mean that the patient was unable to understand the unlawfulness of his action, or to act in accordance with such understanding. The deed itself is considered, without labelling illnesses or persons, seeking a simple definition of immunity from prosecution. The epileptic is immune from prosecution during a full attack, whilst during the rest of the time each case has to be decided individually. We emphasize the necessity of 'declassifying' epilepsy as a typical endogenous psychosis, which puts these patients into the group of the insane, although this term is no longer included in the new legal code. PMID:9147782

  20. The hippocampus is an integral part of the temporal limbic system during emotional processing. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

    NASA Astrophysics Data System (ADS)

    Trost, Wiebke; Frühholz, Sascha

    2015-06-01

    The proposed quartet theory of human emotions by Koelsch and colleagues [1] identifies four different affect systems to be involved in the processing of particular types of emotions. Moreover, the theory integrates both basic emotions and more complex emotion concepts, which include also aesthetic emotions such as musical emotions. The authors identify a particular brain system for each kind of emotion type, also by contrasting them to brain structures that are generally involved in emotion processing irrespective of the type of emotion. A brain system that has been less regarded in emotion theories, but which represents one of the four systems of the quartet to induce attachment related emotions, is the hippocampus.

  1. Effect of baicalin on hippocampal damage in kainic acid-induced epileptic mice

    PubMed Central

    Liao, Zheng-Jian; Liang, Ri-Sheng; Shi, Song-Sheng; Wang, Chun-Hua; Yang, Wei-Zhong

    2016-01-01

    The aim of the present study was to determine the effect of baicalin on the expression of miR-497 and its target B-cell lymphoma-2 (Bcl-2) in the hippocampus of kainic acid (KA)-induced epileptic mice. To establish status epilepticus (SE), 0.1 µg/5 µl KA was injected into the lateral cerebral ventricle in mice, which then received an intraperitoneal injection of baicalin (100 mg/kg) after 1 and 8 h. Hematoxylin and eosin staining was used to observe the pathological changes in morphology and neuronal apoptosis was determined by terminal transferase-mediated dUTP nick end-labeling staining. Western blot analysis was used to detect the expression of Bcl-2 and cleaved caspase-3 proteins in the hippocampus, while reverse transcription-quantitative polymerase chain reaction was used to quantify hippocampal miR-497 expression. The results showed that baicalin significantly attenuated neuronal damage and apoptosis in the hippocampus 72 h after SE. In addition, baicalin decreased SE-induced expression of miR-497 and cleaved caspase-3 protein, while upregulating the expression of Bcl-2 protein. In conclusion, the present results suggest that baicalin possesses potent antiapoptotic properties and attenuates hippocampal injury in mice after SE, which may be associated with the downregulation of miR-497 and cleaved caspase-3 and the upregulation of Bcl-2. PMID:27588062

  2. Epigenetics of Epileptogenesis-Evoked Upregulation of Matrix Metalloproteinase-9 in Hippocampus.

    PubMed

    Zybura-Broda, Katarzyna; Amborska, Renata; Ambrozek-Latecka, Magdalena; Wilemska, Joanna; Bogusz, Agnieszka; Bucko, Joanna; Konopka, Anna; Grajkowska, Wieslawa; Roszkowski, Marcin; Marchel, Andrzej; Rysz, Andrzej; Koperski, Lukasz; Wilczynski, Grzegorz M; Kaczmarek, Leszek; Rylski, Marcin

    2016-01-01

    Enhanced levels of Matrix Metalloproteinase-9 (MMP-9) have been implicated in the pathogenesis of epilepsy in humans and rodents. Lack of Mmp-9 impoverishes, whereas excess of Mmp-9 facilitates epileptogenesis. Epigenetic mechanisms driving the epileptogenesis-related upregulation of MMP-9 expression are virtually unknown. The aim of this study was to reveal these mechanisms. We analyzed hippocampi extracted from adult and pediatric patients with temporal lobe epilepsy as well as from partially and fully pentylenetetrazole kindled rats. We used a unique approach to the analysis of the kindling model results (inclusion in the analysis of rats being during kindling, and not only a group of fully kindled animals), which allowed us to separate the molecular effects exerted by the epileptogenesis from those related to epilepsy and epileptic activity. Consequently, it allowed for a disclosure of molecular mechanisms underlying causes, and not consequences, of epilepsy. Our data show that the epileptogenesis-evoked upregulation of Mmp-9 expression is regulated by removal from Mmp-9 gene proximal promoter of the two, interweaved potent silencing mechanisms-DNA methylation and Polycomb Repressive Complex 2 (PRC2)-related repression. Demethylation depends on a gradual dissociation of the DNA methyltransferases, Dnmt3a and Dnmt3b, and on progressive association of the DNA demethylation promoting protein Gadd45β to Mmp-9 proximal gene promoter in vivo. The PRC2-related mechanism relies on dissociation of the repressive transcription factor YY1 and the dissipation of the PRC2-evoked trimethylation on Lys27 of the histone H3 from the proximal Mmp-9 promoter chromatin in vivo. Moreover, we show that the DNA hydroxymethylation, a new epigenetic DNA modification, which is localized predominantly in the gene promoters and is particularly abundant in the brain, is not involved in a regulation of MMP-9 expression during the epileptogenesis in the rat hippocampus as well as in the

  3. Epigenetics of Epileptogenesis-Evoked Upregulation of Matrix Metalloproteinase-9 in Hippocampus

    PubMed Central

    Zybura-Broda, Katarzyna; Amborska, Renata; Ambrozek-Latecka, Magdalena; Wilemska, Joanna; Bogusz, Agnieszka; Bucko, Joanna; Konopka, Anna; Grajkowska, Wieslawa; Roszkowski, Marcin; Marchel, Andrzej; Rysz, Andrzej; Koperski, Lukasz; Wilczynski, Grzegorz M.; Kaczmarek, Leszek; Rylski, Marcin

    2016-01-01

    Enhanced levels of Matrix Metalloproteinase-9 (MMP-9) have been implicated in the pathogenesis of epilepsy in humans and rodents. Lack of Mmp-9 impoverishes, whereas excess of Mmp-9 facilitates epileptogenesis. Epigenetic mechanisms driving the epileptogenesis-related upregulation of MMP-9 expression are virtually unknown. The aim of this study was to reveal these mechanisms. We analyzed hippocampi extracted from adult and pediatric patients with temporal lobe epilepsy as well as from partially and fully pentylenetetrazole kindled rats. We used a unique approach to the analysis of the kindling model results (inclusion in the analysis of rats being during kindling, and not only a group of fully kindled animals), which allowed us to separate the molecular effects exerted by the epileptogenesis from those related to epilepsy and epileptic activity. Consequently, it allowed for a disclosure of molecular mechanisms underlying causes, and not consequences, of epilepsy. Our data show that the epileptogenesis-evoked upregulation of Mmp-9 expression is regulated by removal from Mmp-9 gene proximal promoter of the two, interweaved potent silencing mechanisms–DNA methylation and Polycomb Repressive Complex 2 (PRC2)-related repression. Demethylation depends on a gradual dissociation of the DNA methyltransferases, Dnmt3a and Dnmt3b, and on progressive association of the DNA demethylation promoting protein Gadd45β to Mmp-9 proximal gene promoter in vivo. The PRC2-related mechanism relies on dissociation of the repressive transcription factor YY1 and the dissipation of the PRC2-evoked trimethylation on Lys27 of the histone H3 from the proximal Mmp-9 promoter chromatin in vivo. Moreover, we show that the DNA hydroxymethylation, a new epigenetic DNA modification, which is localized predominantly in the gene promoters and is particularly abundant in the brain, is not involved in a regulation of MMP-9 expression during the epileptogenesis in the rat hippocampus as well as in the

  4. Expression of Glypican-4 in the brains of epileptic patients and epileptic animals and its effects on epileptic seizures.

    PubMed

    Xiong, Yan; Zhang, Yanke; Zheng, Fangshuo; Yang, Yong; Xu, Xin; Wang, Wei; Zhu, Binglin; Wang, Xuefeng

    2016-09-01

    Glypican-4 (Gpc4) has been found to play an important role in enhancing miniature excitatory postsynaptic currents (mEPSCs). But, the relationship between Gpc4 and epilepsy is still a mystery. In this study, we investigated the expression patterns of Gpc4 in patients with epilepsy and in a pilocarpine-induced rat model of epilepsy. We also determined if altered Gpc4 expression resulted in increased susceptibility to seizures. Western blotting and immunofluorescent methods were utilized. Gpc4 was significantly increased in patients and epileptic rats induced by pilocarpine injection. According to behavioral studies, downregulation of Gpc4 by Gpc4 siRNA decreased spontaneous seizure frequency, while upregulation of Gpc4 by recombinant Gpc4 overexpression led to a converse result. These findings support the hypothesis that increased expression of Gpc4 in the brain is associated with epileptic seizures. PMID:27425250

  5. Coordinated network activity in the hippocampus.

    PubMed

    Draguhn, Andreas; Keller, Martin; Reichinnek, Susanne

    2014-01-01

    The hippocampus expresses a variety of highly organized network states which bind its individual neurons into collective modes of activity. These patterns go along with characteristic oscillations of extracellular potential known as theta, gamma, and ripple oscillations. Such network oscillations share some important features throughout the entire central nervous system of higher animals: they are restricted to a defined behavioral state, they are mostly generated by subthreshold synaptic activity, and they entrain active neurons to fire action potentials at strictly defined phases of the oscillation cycle, thereby providing a unifying 'zeitgeber' for coordinated multineuronal activity. Recent work from the hippocampus of rodents and humans has revealed how the resulting spatiotemporal patterns support the formation of neuronal assemblies which, in our present understanding, form the neuronal correlate of spatial, declarative, or episodic memories. In this review, we introduce the major types of spatiotemporal activity patterns in the hippocampus, describe the underlying neuronal mechanisms, and illustrate the concept of memory formation within oscillating networks. Research on hippocampus-dependent memory has become a key model system at the interface between cellular and cognitive neurosciences. The next step will be to translate our increasing insight into the mechanisms and systemic functions of neuronal networks into urgently needed new therapeutic strategies. PMID:24777128

  6. Unconscious relational encoding depends on hippocampus

    PubMed Central

    Duss, Simone B.; Reber, Thomas P.; Hänggi, Jürgen; Schwab, Simon; Wiest, Roland; Müri, René M.; Brugger, Peter; Gutbrod, Klemens

    2014-01-01

    Textbooks divide between human memory systems based on consciousness. Hippocampus is thought to support only conscious encoding, while neocortex supports both conscious and unconscious encoding. We tested whether processing modes, not consciousness, divide between memory systems in three neuroimaging experiments with 11 amnesic patients (mean age = 45.55 years, standard deviation = 8.74, range = 23–60) and 11 matched healthy control subjects. Examined processing modes were single item versus relational encoding with only relational encoding hypothesized to depend on hippocampus. Participants encoded and later retrieved either single words or new relations between words. Consciousness of encoding was excluded by subliminal (invisible) word presentation. Amnesic patients and controls performed equally well on the single item task activating prefrontal cortex. But only the controls succeeded on the relational task activating the hippocampus, while amnesic patients failed as a group. Hence, unconscious relational encoding, but not unconscious single item encoding, depended on hippocampus. Yet, three patients performed normally on unconscious relational encoding in spite of amnesia capitalizing on spared hippocampal tissue and connections to language cortex. This pattern of results suggests that processing modes divide between memory systems, while consciousness divides between levels of function within a memory system. PMID:25273998

  7. [An epileptic syndrome in infantile cerebral palsy].

    PubMed

    Sumerkina, M L

    1997-01-01

    The results of examination of 102 patients with infantile cerebral paralysis (ICP) with epileptic syndrome (ES) at the age from 3 months to 14 years are presented. Epileptic fits predominated in patients with hemiparetic form of ICP (40.8%) and spastic diplegia (32.4%). ES manifestations were observed in ICP during the first 3 years of life (more than 80% of cases). The peculiarities of ES clinical course were revealed. There were determined the main types of seizures in patients with ICP which depended on age of their manifestation, as well as their further transformation and prognosis. Computer tomographic and EEG-correlations were established in different forms of ICP. They permitted to revealed pathogenetic mechanisms of ES development in patients with ICP and to determine therapeutic policy and prognosis of the disease. PMID:9163254

  8. Localizing epileptic seizure onsets with Granger causality

    NASA Astrophysics Data System (ADS)

    Adhikari, Bhim M.; Epstein, Charles M.; Dhamala, Mukesh

    2013-09-01

    Accurate localization of the epileptic seizure onset zones (SOZs) is crucial for successful surgery, which usually depends on the information obtained from intracranial electroencephalography (IEEG) recordings. The visual criteria and univariate methods of analyzing IEEG recordings have not always produced clarity on the SOZs for resection and ultimate seizure freedom for patients. Here, to contribute to improving the localization of the SOZs and to understanding the mechanism of seizure propagation over the brain, we applied spectral interdependency methods to IEEG time series recorded from patients during seizures. We found that the high-frequency (>80 Hz) Granger causality (GC) occurs before the onset of any visible ictal activity and causal relationships involve the recording electrodes where clinically identifiable seizures later develop. These results suggest that high-frequency oscillatory network activities precede and underlie epileptic seizures, and that GC spectral measures derived from IEEG can assist in precise delineation of seizure onset times and SOZs.

  9. Cognitive and behavioural concerns in epileptic children.

    PubMed

    Tamer, S K

    1999-01-01

    Cognitive performance in an epileptic child has been a difficult issue to predict in day-to-day clinical practice. Several observations made in early and later part of this century do not provide uniform and convincing answer to this issue. Recent trends in research however, have identified certain variables that are shown to be associated with cognitive decline in epileptic children. Together with associated behavioural problems, the resultant school difficulty is the essence of this concern for the parents. The variables related to cognitive deterioration as identified by several studies include underlying brain pathology (symptomatic epilepsy), early age of onset of seizure, severity and intractability of seizure, repeated head trauma, an episode of status epilepticus, presence of interictal subclinical EEG discharge, adverse psychosocial factor and antiepileptic drug (AED). Association of these variables in a given case cannot only predict adverse cognition outcome but also a preventive management package can be planned aiming at avoiding or minimizing these high risk variables. PMID:10798155

  10. The role of inhibition in epileptic networks.

    PubMed

    Trevelyan, Andrew J; Muldoon, Sarah F; Merricks, Edward M; Racca, Claudia; Staley, Kevin J

    2015-06-01

    Inhibition plays many roles in cortical circuits, including coordination of network activity in different brain rhythms and neuronal clusters, gating of activity, gain control, and dictating the manner in which activity flows through the network. This latter is particularly relevant to epileptic states, when extreme hypersynchronous discharges can spread across cortical territories. We review these different physiological and pathological roles and discuss how inhibition can be compromised and why this predisposes the network to seizures. PMID:26035675

  11. Mice doubly-deficient in lysosomal hexosaminidase A and neuraminidase 4 show epileptic crises and rapid neuronal loss.

    PubMed

    Seyrantepe, Volkan; Lema, Pablo; Caqueret, Aurore; Dridi, Larbi; Bel Hadj, Samar; Carpentier, Stephane; Boucher, Francine; Levade, Thierry; Carmant, Lionel; Gravel, Roy A; Hamel, Edith; Vachon, Pascal; Di Cristo, Graziella; Michaud, Jacques L; Morales, Carlos R; Pshezhetsky, Alexey V

    2010-09-01

    Tay-Sachs disease is a severe lysosomal disorder caused by mutations in the HexA gene coding for the α-subunit of lysosomal β-hexosaminidase A, which converts G(M2) to G(M3) ganglioside. Hexa(-/-) mice, depleted of β-hexosaminidase A, remain asymptomatic to 1 year of age, because they catabolise G(M2) ganglioside via a lysosomal sialidase into glycolipid G(A2), which is further processed by β-hexosaminidase B to lactosyl-ceramide, thereby bypassing the β-hexosaminidase A defect. Since this bypass is not effective in humans, infantile Tay-Sachs disease is fatal in the first years of life. Previously, we identified a novel ganglioside metabolizing sialidase, Neu4, abundantly expressed in mouse brain neurons. Now we demonstrate that mice with targeted disruption of both Neu4 and Hexa genes (Neu4(-/-);Hexa(-/-)) show epileptic seizures with 40% penetrance correlating with polyspike discharges on the cortical electrodes of the electroencephalogram. Single knockout Hexa(-/-) or Neu4(-/-) siblings do not show such symptoms. Further, double-knockout but not single-knockout mice have multiple degenerating neurons in the cortex and hippocampus and multiple layers of cortical neurons accumulating G(M2) ganglioside. Together, our data suggest that the Neu4 block exacerbates the disease in Hexa(-/-) mice, indicating that Neu4 is a modifier gene in the mouse model of Tay-Sachs disease, reducing the disease severity through the metabolic bypass. However, while disease severity in the double mutant is increased, it is not profound suggesting that Neu4 is not the only sialidase contributing to the metabolic bypass in Hexa(-/-) mice. PMID:20862357

  12. Effect of GABA(B) receptor agonist SKF97541 on cortical and hippocampal epileptic afterdischarges.

    PubMed

    Fábera, P; Mareš, P

    2014-01-01

    Activation of GABA(B) receptors leads to longer inhibitory postsynaptic potentials than activation of GABA(A) receptors. Therefore GABA(B) receptors may be a target for anticonvulsant therapy. The present study examined possible effects of GABA(B) receptor agonist SKF97541 on cortical and hippocampal epileptic afterdischarges (ADs). Epileptic ADs elicited by electrical stimulation of sensorimotor cortex or dorsal hippocampus were studied in adult male Wistar rats. Stimulation series were applied 6 times with 10- or 20-min interval. Either interval was efficient for reliable elicitation of cortical ADs but stimulation at 10-min intervals did not reliably elicit hippocampal ADs, many stimulations were without effect. SKF97541 in dose 1 mg/kg significantly prolonged cortical ADs. Duration of hippocampal ADs was not significantly changed by either dose of SKF97541 in spite of a marked myorelaxant effect of the higher dose. Our present data demonstrated that neither cortical nor hippocampal ADs in adult rats were suppressed by GABA(B) receptor agonist SKF97541. Proconvulsant effect on cortical ADs indicates a different role in these two brain structures. In addition, duration of refractory period for electrically-induced ADs in these two structures in adult rats is different. PMID:24702499

  13. Phase-Synchronization Early Epileptic Seizure Detector VLSI Architecture.

    PubMed

    Abdelhalim, K; Smolyakov, V; Genov, R

    2011-10-01

    A low-power VLSI processor architecture that computes in real time the magnitude and phase-synchronization of two input neural signals is presented. The processor is a part of an envisioned closed-loop implantable microsystem for adaptive neural stimulation. The architecture uses three CORDIC processing cores that require shift-and-add operations but no multiplication. The 10-bit processor synthesized and prototyped in a standard 1.2 V 0.13 μm CMOS technology utilizes 41,000 logic gates. It dissipates 3.6 μW per input pair, and provides 1.7 kS/s per-channel throughput when clocked at 2.5 MHz. The power scales linearly with the number of input channels or the sampling rate. The efficacy of the processor in early epileptic seizure detection is validated on human intracranial EEG data. PMID:23852175

  14. The multi-instrumentalist hippocampus. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

    NASA Astrophysics Data System (ADS)

    Strange, Bryan A.; Yebra, Mar

    2015-06-01

    Characterizing the neural circuitry of emotion is important not only from a basic science perspective, but also for understanding how these circuits may malfunction in psychiatric disease. A fundamental question for affective neuroscience is whether there are specialised neuroanatomical areas, or "modules", dedicated to the processing of emotional stimuli. In their review, Koelsch and colleagues [1] argue for the existence of a quartet of neuroanatomically distinct cerebral systems involved in the generation of a specific class of affects. Intriguingly, all four systems (brainstem-, diencephalon-, hippocampus-, and orbitofrontal-centred) comprise brain areas whose role in emotional processing is in addition to mediating other specific aspects of cognition. One member of the quartet in which this is particularly apparent is the hippocampus, a structure known to be critical for episodic memory and navigation. If areas involved in emotion also mediate other brain functions, this raises an issue of whether these multiple functions are executed by segregated circuits within each structure - i.e., a "module" for emotion residing in a sub-division of a brain structure - or whether these circuits are superimposed.

  15. Interleukin-1β biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice.

    PubMed

    Maroso, Mattia; Balosso, Silvia; Ravizza, Teresa; Iori, Valentina; Wright, Christopher Ian; French, Jacqueline; Vezzani, Annamaria

    2011-04-01

    Experimental evidence and clinical observations indicate that brain inflammation is an important factor in epilepsy. In particular, induction of interleukin-converting enzyme (ICE)/caspase-1 and activation of interleukin (IL)-1β/IL-1 receptor type 1 axis both occur in human epilepsy, and contribute to experimentally induced acute seizures. In this study, the anticonvulsant activity of VX-765 (a selective ICE/caspase-1 inhibitor) was examined in a mouse model of chronic epilepsy with spontaneous recurrent epileptic activity refractory to some common anticonvulsant drugs. Moreover, the effects of this drug were studied in one acute model of seizures in mice, previously shown to involve activation of ICE/caspase-1. Quantitative analysis of electroencephalogram activity was done in mice exposed to acute seizures or those developing chronic epileptic activity after status epilepticus to assess the anticonvulsant effects of systemic administration of VX-765. Histological and immunohistochemical analysis of brain tissue was carried out at the end of pharmacological experiments in epileptic mice to evaluate neuropathology, glia activation and IL-1β expression, and the effect of treatment. Repeated systemic administration of VX-765 significantly reduced chronic epileptic activity in mice in a dose-dependent fashion (12.5-200 mg/kg). This effect was observed at doses ≥ 50 mg/kg, and was reversible with discontinuation of the drug. Maximal drug effect was associated with inhibition of IL-1β synthesis in activated astrocytes. The same dose regimen of VX-765 also reduced acute seizures in mice and delayed their onset time. These results support a new target system for anticonvulsant pharmacological intervention to control epileptic activity that does not respond to some common anticonvulsant drugs. PMID:21431948

  16. Impaired picture recognition in transient epileptic amnesia.

    PubMed

    Dewar, Michaela; Hoefeijzers, Serge; Zeman, Adam; Butler, Christopher; Della Sala, Sergio

    2015-01-01

    Transient epileptic amnesia (TEA) is an epileptic syndrome characterized by recurrent, brief episodes of amnesia. Transient epileptic amnesia is often associated with the rapid decline in recall of new information over hours to days (accelerated long-term forgetting - 'ALF'). It remains unknown how recognition memory is affected in TEA over time. Here, we report a systematic study of picture recognition in patients with TEA over the course of one week. Sixteen patients with TEA and 16 matched controls were presented with 300 photos of everyday life scenes. Yes/no picture recognition was tested 5min, 2.5h, 7.5h, 24h, and 1week after picture presentation using a subset of target pictures as well as similar and different foils. Picture recognition was impaired in the patient group at all test times, including the 5-minute test, but it declined normally over the course of 1week. This impairment was associated predominantly with an increased false alarm rate, especially for similar foils. High performance on a control test indicates that this impairment was not associated with perceptual or discrimination deficits. Our findings suggest that, at least in some TEA patients with ALF in verbal recall, picture recognition does not decline more rapidly than in controls over 1week. However, our findings of an early picture recognition deficit suggest that new visual memories are impoverished after minutes in TEA. This could be the result of deficient encoding or impaired early consolidation. The early picture recognition deficit observed could reflect either the early stages of the process that leads to ALF or a separable deficit of anterograde memory in TEA. Lastly, our study suggests that at least some patients with TEA are prone to falsely recognizing new everyday visual information that they have not in fact seen previously. This deficit, alongside their ALF in free recall, likely affects everyday memory performance. PMID:25506793

  17. [Intracranial tumors and epileptic seizures: treatment principles].

    PubMed

    Rossetti, Andrea O; Vulliémoz, Serge

    2016-04-27

    Epileptic seizures represent a relatively frequent issue in patients with intracranial neoplasms, and very frequently imply the start of an antiepileptic treatment as secondary prophylaxis. Even if the current level of evidence is relatively low, compounds with a limited risk of pharmacokinetic interactions are clearly preferred. Levetiracetam is probably the most prescribed agent in this setting, while pregabalin, valproate, lacosamide and lamotrigine are valuable alternatives. The treatment choice has to consider the different profiles of side effects and should be tailored to each patient. In this setting, a multidisciplinary approach including general practicioner, oncologist and neurologist is strongly advocated. PMID:27281943

  18. Optical imaging of visual cortex epileptic foci and propagation pathways.

    PubMed

    Haglund, Michael M

    2012-06-01

    Precise localization of neocortical epileptic foci is a complex problem that usually requires ictal video-electroencephalography (EEG) recordings; high-resolution magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT) studies; and/or invasive monitoring with implanted grid array electrodes. The exact ictal-onset site must be identified and removed to obtain the best opportunity for a seizure-free outcome. The goal of this study was to determine if high-resolution optical imaging could precisely identify neocortical epileptic foci and what role underlying neuroanatomic pathways played in the seizure propagation. Small acute epileptic foci (0.5 × 0.5 mm(2) ) were created in the primate visual neocortex and single-unit and surface EEG recordings were combined with optical imaging of voltage-sensitive dye changes. Brief visual stimulation was used to evoke interictal bursts. In addition, different visually evoked epileptiform bursts were analyzed to determine the location of the epileptic focus. Spike-triggered averaging of the optical images associated with the surface EEG interictal bursts were analyzed to determine the exact location of the epileptic focus. Specific orientations of brief visual stimulation evoked different intensity optical changes and precisely localized the epileptic focus. Optical imaging identified individual epileptic foci that were <3 mm apart. The development of individual epileptic focus was monitored with optical imaging, which demonstrated excitatory activity at the focus with a surrounding zone of inhibitory-like activity. Propagation pathways outside of the inhibitory-like surround demonstrated alternating bands of excitation and inhibition with a pattern orthogonal to the ocular dominance columns. This experimental study demonstrates that optical imaging can precisely localize an epileptic focus, and provides excellent spatial resolution of the changes that

  19. Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy.

    PubMed

    Karlócai, Mária R; Wittner, Lucia; Tóth, Kinga; Maglóczky, Zsófia; Katarova, Zoja; Rásonyi, György; Erőss, Loránd; Czirják, Sándor; Halász, Péter; Szabó, Gábor; Payne, John A; Kaila, Kai; Freund, Tamás F

    2016-09-01

    Synaptic reorganization in the epileptic hippocampus involves altered excitatory and inhibitory transmission besides the rearrangement of dendritic spines, resulting in altered excitability, ion homeostasis, and cell swelling. The potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in neurons and hence will play a prominent role in determining the polarity of GABAA receptor-mediated chloride currents. In addition, KCC2 also interacts with the actin cytoskeleton which is critical for dendritic spine morphogenesis, and for the maintenance of glutamatergic synapses and cell volume. Using immunocytochemistry, we examined the cellular and subcellular levels of KCC2 in surgically removed hippocampi of temporal lobe epilepsy (TLE) patients and compared them to control human tissue. We also studied the distribution of KCC2 in a pilocarpine mouse model of epilepsy. An overall increase in KCC2-expression was found in epilepsy and confirmed by Western blots. The cellular and subcellular distributions in control mouse and human samples were largely similar; moreover, changes affecting KCC2-expression were also alike in chronic epileptic human and mouse hippocampi. At the subcellular level, we determined the neuronal elements exhibiting enhanced KCC2 expression. In epileptic tissue, staining became more intense in the immunopositive elements detected in control tissue, and profiles with subthreshold expression of KCC2 in control samples became labelled. Positive interneuron somata and dendrites were more numerous in epileptic hippocampi, despite severe interneuron loss. Whether the elevation of KCC2-expression is ultimately a pro- or anticonvulsive change, or both-behaving differently during ictal and interictal states in a context-dependent manner-remains to be established. PMID:26427846

  20. Contributions of the hippocampus to feedback learning.

    PubMed

    Dickerson, Kathryn C; Delgado, Mauricio R

    2015-12-01

    Humans learn about the world in a variety of manners, including by observation, by associating cues in the environment, and via feedback. Across species, two brain structures have been predominantly involved in these learning processes: the hippocampus--supporting learning via observation and paired association--and the striatum--critical for feedback learning. This simple dichotomy, however, has recently been challenged by reports of hippocampal engagement in feedback learning, although the role of the hippocampus is not fully understood. The purpose of this experiment was to characterize the hippocampal response during feedback learning by manipulating varying levels of memory interference. Consistent with prior reports, feedback learning recruited the striatum and midbrain. Notably, feedback learning also engaged the hippocampus. The level of activity in these regions was modulated by the degree of memory interference, such that the greatest activation occurred during the highest level of memory interference. Importantly, the accuracy of information learned via feedback correlated with hippocampal activation and was reduced by the presence of high memory interference. Taken together, these findings provide evidence of hippocampal involvement in feedback learning by demonstrating both its relevance for the accuracy of information learned via feedback and its susceptibility to interference. PMID:26055632

  1. Oxidative Status in Epileptic Children Using Carbamazepine

    PubMed Central

    Tutanc, Murat; Aras, Mustafa; Dokuyucu, Recep; Altas, Murat; Zeren, Cem; Arica, Vefik; Ozturk, Oktay Hasan; Motor, Sedat; Yilmaz, Cahide

    2015-01-01

    Background: There is an increasing attention towards the relationship between oxidative stress and epilepsy. The effect of antiepileptic drugs on oxidant status is of major interest. Antiepileptic drugs can increase levels of free radicals, which consequently might lead to seizures. Carbamazepine (CBZ) is an antiepileptic drug commonly used in childhood and adolescence. Objectives: Therefore we aimed to investigate the effects of CBZ on total antioxidant status, total oxidant stress, and oxidative stress index. Patients and Methods: The study included 40 epileptic patients and 31 healthy children between 4 and 12 years of age. Serum CBZ level, total antioxidant capacity and total oxidant status were measured. Oxidative stress index was also calculated both in controls and patients. Results: In the epileptic group, decreased levels of total antioxidant capacity, increased total oxidative stress and oxidative stress index levels were found. Positive correlation between plasma CBZ levels and total oxidant status was observed. Conclusions: Antioxidant action could not be playing any role in antiepileptic effect of CBZ. Furthermore, increased oxidative stress induced by CBZ could be the cause of CBZ-induced seizures. Therefore combining CBZ with antioxidants could be beneficial. PMID:26635944

  2. Epileptic Seizure Detection and Warning Device

    SciTech Connect

    Elarton, J.K.; Koepsel, K.L.

    1999-06-21

    Flint Hills Scientific, L.L.C. (FHS) has invented what is believed to be the first real-time epileptic seizure detection and short-term prediction method in the world. They have demonstrated an IBM PC prototype with a multi-channel EEG monitoring configuration. This CRADA effort applied AlliedSignal FM and T hardware design, manufacturing miniaturization, and high quality manufacturing expertise in converting the prototype into a small, portable, self-contained, multi-channel EEG epileptic seizure detection and warning device. The purpose of this project was to design and build a proof-of-concept miniaturized prototype of the FHS-developed PC-based prototype. The resultant DSP prototype, measuring 4'' x 6'' x 2'', seizure detection performance compared favorably with the FHS PC prototype, thus validating the DSP design goals. The very successful completion of this project provided valuable engineering information for FHS for future prototype commercialization as well as providing AS/FM and T engineers DSP design experience.

  3. The Piriform Cortex and Human Focal Epilepsy

    PubMed Central

    Vaughan, David N.; Jackson, Graeme D.

    2014-01-01

    It is surprising that the piriform cortex, when compared to the hippocampus, has been given relatively little significance in human epilepsy. Like the hippocampus, it has a phylogenetically preserved three-layered cortex that is vulnerable to excitotoxic injury, has broad connections to both limbic and cortical areas, and is highly epileptogenic – being critical to the kindling process. The well-known phenomenon of early olfactory auras in temporal lobe epilepsy highlights its clinical relevance in human beings. Perhaps because it is anatomically indistinct and difficult to approach surgically, as it clasps the middle cerebral artery, it has, until now, been understandably neglected. In this review, we emphasize how its unique anatomical and functional properties, as primary olfactory cortex, predispose it to involvement in focal epilepsy. From recent convergent findings in human neuroimaging, clinical epileptology, and experimental animal models, we make the case that the piriform cortex is likely to play a facilitating and amplifying role in human focal epileptogenesis, and may influence progression to epileptic intractability. PMID:25538678

  4. Dual mechanisms of rapid expression of anxiety-related behavior in pilocarpine-treated epileptic mice.

    PubMed

    Otsuka, Shintaro; Ohkido, Taro; Itakura, Makoto; Watanabe, Shigeru; Yamamori, Saori; Iida, Yuuki; Saito, Masanori; Miyaoka, Hitoshi; Takahashi, Masami

    2016-07-01

    A mouse model of epilepsy was generated by inducing status epilepticus (SE) for either 1.5 or 4.5h with pilocarpine to study anxiety-related behaviors, changes in the electroencephalogram of the cerebral cortex and hippocampus, and expression of hippocampal proteins. The viability and rate of success of SE induction were high in C57BL/6N mice but not in C57BL/6J mice. C57BL/6N mice were immotile during the first 2days after SE; however, by the third day, most mice were recovered and exhibited strong anxiety-related behaviors in response to the light/dark preference test and open field test. There was a striking difference in the temporal appearance of anxiety-related behavior between the two SE durations: 1.5h SE mice exhibited strong anxiety-related behavior 3days after SE that gradually attenuated over the next few weeks, whereas 4.5h SE mice exhibited strong anxiety-related behavior 3days after SE that persisted even at nearly 1year after SE. Mice receiving both SE durations exhibited generalized seizures (GS) after SE; however, there was a marked difference in the timing and duration of GS appearance. Mice in the 4.5h SE group exhibited spontaneous GS from 4days to at least 96days after SE. In contrast, mice in the 1.5h SE group exhibited GS only within the first several days after SE; however, epileptic spike clusters continuously appeared in the cerebral cortex and hippocampus for up to twelve days after SE. Among the hippocampal proteins tested, only brain derived-neurotrophic factor (BDNF) exhibited altered expression in parallel with anxiety-related behavior. These results showed the possibility that BDNF expression in the hippocampus might cause anxiety-related behavior in adulthood. PMID:27132018

  5. MMPI-2 profiles: fibromyalgia patients compared to epileptic and non-epileptic seizure patients.

    PubMed

    Johnson, Amy L; Storzbach, Daniel; Binder, Laurence M; Barkhuizen, André; Kent Anger, W; Salinsky, Martin C; Tun, Saw-Myo; Rohlman, Diane S

    2010-02-01

    We compared MMPI-2 profiles of Gulf War veterans with fibromyalgia (FM) to epileptic seizure (ES) patients, psychogenic non-epileptic seizure (PNES) patients, and Gulf War veteran healthy controls. Both PNES and FM are medically unexplained conditions. In previous MMPI-2 research PNES patients were shown to have significantly higher Hs and Hy clinical scales than ES patients. In the present research the FM group had significantly higher Hs and Hy scale scores than both the ES group and the healthy control group. There was no significant difference between the FM and PNES Hs scale scores; however, the FM Hy scale score was significantly lower than the PNES Hy scale score. Present findings indicate a high level of psychological distress in the FM group. PMID:19859855

  6. Distribution entropy analysis of epileptic EEG signals.

    PubMed

    Li, Peng; Yan, Chang; Karmakar, Chandan; Liu, Changchun

    2015-08-01

    It is an open-ended challenge to accurately detect the epileptic seizures through electroencephalogram (EEG) signals. Recently published studies have made elaborate attempts to distinguish between the normal and epileptic EEG signals by advanced nonlinear entropy methods, such as the approximate entropy, sample entropy, fuzzy entropy, and permutation entropy, etc. Most recently, a novel distribution entropy (DistEn) has been reported to have superior performance compared with the conventional entropy methods for especially short length data. We thus aimed, in the present study, to show the potential of DistEn in the analysis of epileptic EEG signals. The publicly-accessible Bonn database which consisted of normal, interictal, and ictal EEG signals was used in this study. Three different measurement protocols were set for better understanding the performance of DistEn, which are: i) calculate the DistEn of a specific EEG signal using the full recording; ii) calculate the DistEn by averaging the results for all its possible non-overlapped 5 second segments; and iii) calculate it by averaging the DistEn values for all the possible non-overlapped segments of 1 second length, respectively. Results for all three protocols indicated a statistically significantly increased DistEn for the ictal class compared with both the normal and interictal classes. Besides, the results obtained under the third protocol, which only used very short segments (1 s) of EEG recordings showed a significantly (p <; 0.05) increased DistEn for the interictal class in compassion with the normal class, whereas both analyses using relatively long EEG signals failed in tracking this difference between them, which may be due to a nonstationarity effect on entropy algorithm. The capability of discriminating between the normal and interictal EEG signals is of great clinical relevance since it may provide helpful tools for the detection of a seizure onset. Therefore, our study suggests that the Dist

  7. Resetting of Brain Dynamics: Epileptic versus Psychogenic Non-Epileptic Seizures

    PubMed Central

    Krishnan, Balu; Faith, Aaron; Vlachos, Ioannis; Roth, Austin; Williams, Korwyn; Noe, Katie; Drazkowski, Joe; Tapsell, Lisa; Sirven, Joseph; Iasemidis, Leon

    2011-01-01

    In this study, we investigated the possibility of differential diagnosis of patients with epileptic seizures (ES) and patients with psychogenic non-epileptic seizures (PNES) by an advanced analysis of dynamics of the patients' scalp electroencephalograms (EEG). The underlying principle was the presence of resetting of brain's pre-ictal spatiotemporal entrainment following onset of ES and the absence of resetting following PNES. Long-term (days) scalp EEGs recorded from five ES and six PNES patients were analyzed. It was found that: (a) Pre-ictal entrainment of brain sites was reset by epileptic seizures (p<0.05) in 4 out of the 5 patients with ES, and not reset (p=0.28) in the fifth patient. (b) Resetting did not occur (p>0.1) in any of the 6 patients with PNES. These preliminary results in patients with ES are in agreement with our previous findings from intracranial EEG recordings on resetting of brain dynamics at ES and it is expected to constitute the basis for the development of a reliable and supporting tool in the differential diagnosis between ES and PNES. Finally, we believe that these results shed a novel light on the electrophysiology of psychogenic epilepsy by showing that occurrence of PNES does not assist patients to overcome a pathological entrainment of brain dynamics. PMID:22078523

  8. The diagnosis of psychogenic non-epileptic seizures: a review.

    PubMed

    Kuyk, J; Leijten, F; Meinardi, H; Spinhoven; Van Dyck, R

    1997-08-01

    Diagnosing psychogenic non-epileptic seizures (PNES) is a clinical challenge. There is neither a standard in diagnosing PNES nor a comprehensive theoretical framework for this type of seizure. The diagnosis of PNES must be made by excluding epilepsy. However, epilepsy cannot always be determined and PNES and epileptic seizures may coexist. In this study, the characteristics of PNES and patients are discussed. The diagnosis of PNES and epileptic seizures was facilitated by the simultaneous recording of seizures on video tape and EEG. Seizure provoking techniques, hormonal indices, and psychological methods were also used. The benefits and limitations of these techniques are discussed and proposals are made for clinical guidelines. PMID:9304716

  9. [Clinical presentation and diagnosis of epileptic auras].

    PubMed

    Barletova, E I; Kremenchugskaia, M R; Mukhin, K Iu; Glukhova, L Iu; Mironov, M B

    2012-01-01

    To define clinical presentations of visual auras and to reveal their clinical, encephalographic and neuroimaging correlates, we examined 23 patients, aged from 5 to 25 years (mean 14±6 years), with focal forms of epilepsy. Patients had visual auras regardless of the etiology of epilepsy which developed immediately before epileptic seizures or were isolated. Patients had simple or complex visual hallucinations, the former occurring more frequently, visual illusions and ictal amaurosis. Positive visual phenomena were noted more frequently than negative ones. In most of the patients, visual hallucinations were associated with the pathological activity in cortical occipital regions of the brain and, in some cases, in temporal and parietal regions. The different pathologies (developmental defects, post-ischemic, atrophic and other disturbances) identified by MRI were found in a half of patients. PMID:23120768

  10. Advances in anti-epileptic drug testing.

    PubMed

    Krasowski, Matthew D; McMillin, Gwendolyn A

    2014-09-25

    In the past twenty-one years, 17 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are clobazam, ezogabine (retigabine), eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. Therapeutic drug monitoring is often used in the clinical dosing of the newer anti-epileptic drugs. The drugs with the best justifications for drug monitoring are lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and zonisamide. Perampanel, stiripentol and tiagabine are strongly bound to serum proteins and are candidates for monitoring of the free drug fractions. Alternative specimens for therapeutic drug monitoring are saliva and dried blood spots. Therapeutic drug monitoring of the new antiepileptic drugs is discussed here for managing patients with epilepsy. PMID:24925169

  11. Epileptic Seizure Forewarning by Nonlinear Techniques

    SciTech Connect

    Hively, LM

    2001-02-05

    Nicolet Biomedical Inc. (NBI) is collaborating with Oak Ridge National Laboratory (ORNL) under a Cooperative Research and Development Agreement (CRADA) to convert ORNL.s patented technology for forewarning of epileptic seizures to a clinical prototype. This technical report describes the highlights of the first year.s effort. The software requirements for the clinical device were specified from which the hardware specifications were obtained. ORNL's research-class FORTRAN was converted to run under a graphical user interface (GUI) that was custom-built for this application by NBI. The resulting software package was cloned to desktop computers that are being tested in five different clinical sites. Two hundred electroencephalogram (EEG) datasets from those clinical sites were provided to ORNL for detailed analysis and improvement of the forewarning methodology. Effort under this CRADA is continuing into the second year as planned.

  12. [Neurotic states in children with epileptic parents].

    PubMed

    Rogacheva, T A; Boldyrev, A I

    1986-01-01

    On the basis of neurological, encephalographic and clinico-anamnestic examinations of 106 children with a family history of epilepsy the authors have specified a group of children (n = 38) suffering from different neurotic disorders which included neurotic ticks, sleep disturbances, affective-shock reactions and signs of asthenization. The role of familial factors in the formation of neurotic states of children is emphasized. The authors consider the time during which the child was exposed to psychotraumatic circumstances and the relationship between the severity of epileptic process in parents and the development of neurotic disorders in their progeny. A conclusion has been made that the disease of the parents can exert both direct and indirect influence on the nervous system of the child, this leading to the development of different neurotic states. The prophylaxis of neurotic disturbances in children should include the creation of healthy psychic atmosphere in families where one of the parents suffers from epilepsy. PMID:3751410

  13. The hippocampus in aging and disease: From plasticity to vulnerability.

    PubMed

    Bartsch, T; Wulff, P

    2015-11-19

    The hippocampus has a pivotal role in learning and in the formation and consolidation of memory and is critically involved in the regulation of emotion, fear, anxiety, and stress. Studies of the hippocampus have been central to the study of memory in humans and in recent years, the regional specialization and organization of hippocampal functions have been elucidated in experimental models and in human neurological and psychiatric diseases. The hippocampus has long been considered a classic model for the study of neuroplasticity as many examples of synaptic plasticity such as long-term potentiation and -depression have been identified and demonstrated in hippocampal circuits. Neuroplasticity is the ability to adapt and reorganize the structure or function to internal or external stimuli and occurs at the cellular, population, network or behavioral level and is reflected in the cytological and network architecture as well as in intrinsic properties of hippocampal neurons and circuits. The high degree of hippocampal neuroplasticity might, however, be also negatively reflected in the pronounced vulnerability of the hippocampus to deleterious conditions such as ischemia, epilepsy, chronic stress, neurodegeneration and aging targeting hippocampal structure and function and leading to cognitive deficits. Considering this framework of plasticity and vulnerability, we here review basic principles of hippocampal anatomy and neuroplasticity on various levels as well as recent findings regarding the functional organization of the hippocampus in light of the regional vulnerability in Alzheimer's disease, ischemia, epilepsy, neuroinflammation and aging. PMID:26241337

  14. Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy.

    PubMed

    Doná, Flávia; Conceição, Isaltino Marcelo; Ulrich, Henning; Ribeiro, Eliane Beraldi; Freitas, Thalma Ariani; Nencioni, Ana Leonor Abrahao; da Silva Fernandes, Maria José

    2016-06-01

    Although purinergic receptor activity has lately been associated with epilepsy, little is known about the exact role of purines in epileptogenesis. We have used a rat model of temporal lobe epilepsy induced by pilocarpine to study the dynamics of purine metabolism in the hippocampus during different times of status epilepticus (SE) and the chronic phase. Concentrations of adenosine 5'-triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine in normal and epileptic rat hippocampus were determined by microdialysis in combination with high-performance liquid chromatography (HPLC). Extracellular ATP concentrations did not vary along 4 h of SE onset. However, AMP concentration was elevated during the second hour, whereas ADP and adenosine concentrations augmented during the third and fourth hour following SE. During chronic phase, extracellular ATP, ADP, AMP, and adenosine concentrations decreased, although these levels again increased significantly during spontaneous seizures. These results suggest that the increased turnover of ATP during the acute period is a compensatory mechanism able to reduce the excitatory role of ATP. Increased adenosine levels following 4 h of SE may contribute to block seizures. On the other hand, the reduction of purine levels in the hippocampus of chronic epileptic rats may result from metabolic changes and be part of the mechanisms involved in the onset of spontaneous seizures. This work provides further insights into purinergic signaling during establishment and chronic phase of epilepsy. PMID:26939579

  15. Hippocampus, microcircuits and associative memory.

    PubMed

    Cutsuridis, Vassilis; Wennekers, Thomas

    2009-10-01

    The hippocampus is one of the most widely studied brain region. One of its functional roles is the storage and recall of declarative memories. Recent hippocampus research has yielded a wealth of data on network architecture, cell types, the anatomy and membrane properties of pyramidal cells and interneurons, and synaptic plasticity. Understanding the functional roles of different families of hippocampal neurons in information processing, synaptic plasticity and network oscillations poses a great challenge but also promises deep insight into one of the major brain systems. Computational and mathematical models play an instrumental role in exploring such functions. In this paper, we provide an overview of abstract and biophysical models of associative memory with particular emphasis on the operations performed by the diverse (inter)neurons in encoding and retrieval of memories in the hippocampus. PMID:19647982

  16. De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy.

    PubMed

    Syrbe, Steffen; Hedrich, Ulrike B S; Riesch, Erik; Djémié, Tania; Müller, Stephan; Møller, Rikke S; Maher, Bridget; Hernandez-Hernandez, Laura; Synofzik, Matthis; Caglayan, Hande S; Arslan, Mutluay; Serratosa, José M; Nothnagel, Michael; May, Patrick; Krause, Roland; Löffler, Heidrun; Detert, Katja; Dorn, Thomas; Vogt, Heinrich; Krämer, Günter; Schöls, Ludger; Mullis, Primus E; Linnankivi, Tarja; Lehesjoki, Anna-Elina; Sterbova, Katalin; Craiu, Dana C; Hoffman-Zacharska, Dorota; Korff, Christian M; Weber, Yvonne G; Steinlin, Maja; Gallati, Sabina; Bertsche, Astrid; Bernhard, Matthias K; Merkenschlager, Andreas; Kiess, Wieland; Gonzalez, Michael; Züchner, Stephan; Palotie, Aarno; Suls, Arvid; De Jonghe, Peter; Helbig, Ingo; Biskup, Saskia; Wolff, Markus; Maljevic, Snezana; Schüle, Rebecca; Sisodiya, Sanjay M; Weckhuysen, Sarah; Lerche, Holger; Lemke, Johannes R

    2015-04-01

    Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features. Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel KV1.2, in six isolated patients with epileptic encephalopathy (one mutation recurred three times independently). Four individuals presented with febrile and multiple afebrile, often focal seizure types, multifocal epileptiform discharges strongly activated by sleep, mild to moderate intellectual disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype. They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing neurons. PMID:25751627

  17. De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy

    PubMed Central

    Müller, Stephan; Møller, Rikke S.; Maher, Bridget; Hernandez-Hernandez, Laura; Synofzik, Matthis; Caglayan, Hande S.; Arslan, Mutluay; Serratosa, José M.; Nothnagel, Michael; May, Patrick; Krause, Roland; Löffler, Heidrun; Detert, Katja; Dorn, Thomas; Vogt, Heinrich; Krämer, Günter; Schöls, Ludger; Mullis, Primus E.; Linnankivi, Tarja; Lehesjoki, Anna-Elina; Sterbova, Katalin; Craiu, Dana C.; Hoffman-Zacharska, Dorota; Korff, Christian M.; Weber, Yvonne G.; Steinlin, Maja; Gallati, Sabina; Bertsche, Astrid; Bernhard, Matthias K.; Merkenschlager, Andreas; Kiess, Wieland; Gonzalez, Michael; Züchner, Stephan; Palotie, Aarno; Suls, Arvid; De Jonghe, Peter; Helbig, Ingo; Biskup, Saskia; Wolff, Markus; Maljevic, Snezana; Schüle, Rebecca; Sisodiya, Sanjay M.; Weckhuysen, Sarah; Lerche, Holger; Lemke, Johannes R.

    2015-01-01

    Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features1-6. Using next generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel KV1.2, in six patients with epileptic encephalopathy (one mutation recurred three times independently). Four individuals presented with febrile and multiple afebrile, often focal seizure types, multifocal epileptiform discharges strongly activated by sleep, mild-moderate intellectual disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype revealed an almost complete loss-of-function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype. They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a novel gene involved in human neurodevelopmental disorders by two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing neurons. PMID:25751627

  18. Neurogenesis in a young dog with epileptic seizures.

    PubMed

    Borschensky, C M; Woolley, J S; Kipar, A; Herden, C

    2012-09-01

    Epileptic seizures can lead to various reactions in the brain, ranging from neuronal necrosis and glial cell activation to focal structural disorganization. Furthermore, increased hippocampal neurogenesis has been documented in rodent models of acute convulsions. This is a report of hippocampal neurogenesis in a dog with spontaneous epileptic seizures. A 16-week-old epileptic German Shepherd Dog had marked neuronal cell proliferation (up to 5 mitotic figures per high-power field and increased immunohistochemical expression of proliferative cell nuclear antigen) in the dentate gyrus accompanied by microglial and astroglial activation. Some granule cells expressed doublecortin, a marker of immature neurons; mitotically active cells expressed neuronal nuclear antigen. No mitotic figures were found in the brain of age-matched control dogs. Whether increased neurogenesis represents a general reaction pattern of young epileptic dogs should be investigated. PMID:22194355

  19. The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies.

    PubMed

    Shbarou, Rolla; Mikati, Mohamad A

    2016-05-01

    Pediatric epileptic encephalopathies represent a clinically challenging and often devastating group of disorders that affect children at different stages of infancy and childhood. With the advances in genetic testing and neuroimaging, the etiologies of these epileptic syndromes are now better defined. The various encephalopathies that are reviewed in this article include the following: early infantile epileptic encephalopathy or Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome, severe myoclonic epilepsy in infancy (Dravet syndrome), Landau-Kleffner syndrome, Lennox-Gastaut syndrome, and epileptic encephalopathy with continuous spike-and-wave during sleep. Their clinical features, prognosis as well as underlying genetic etiologies are presented and updated. PMID:27544470

  20. Epileptic encephalopathies: Optimizing seizure control and developmental outcome.

    PubMed

    Jehi, Lara; Wyllie, Elaine; Devinsky, Orrin

    2015-10-01

    Cognitive and developmental outcomes in patients with epileptic encephalopathy are hypothesized to result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent and repetitive seizures and epileptiform discharges that often straddle the interictal and ictal boundaries. This article briefly reviews the evidence related to this assumption, presents critical questions that need to be answered to clarify this relationship, and advances a set of concrete steps that may help improve developmental patient outcomes. PMID:26293588

  1. Classifying Normal and Abnormal Status Based on Video Recordings of Epileptic Patients

    PubMed Central

    Li, Jing; Zhen, Xiantong; Liu, Xianzeng

    2014-01-01

    Based on video recordings of the movement of the patients with epilepsy, this paper proposed a human action recognition scheme to detect distinct motion patterns and to distinguish the normal status from the abnormal status of epileptic patients. The scheme first extracts local features and holistic features, which are complementary to each other. Afterwards, a support vector machine is applied to classification. Based on the experimental results, this scheme obtains a satisfactory classification result and provides a fundamental analysis towards the human-robot interaction with socially assistive robots in caring the patients with epilepsy (or other patients with brain disorders) in order to protect them from injury. PMID:24977196

  2. Two types of isolated epileptic nystagmus: case report

    PubMed Central

    Ma, Yunfeng; Wang, Juan; Li, Desheng; Lang, Senyang

    2015-01-01

    Epileptic nystagmus (EN) is a quick, repetitive jerky movement of the eyeball caused by seizure activity, unaccompanied by other ictal phenomena rare. Here, we described two cases, one characterized by binocular and the other by monocular isolated epileptic nystagmus (IEN), and we identified the characteristics of the etiology, clinical manifestations, electroencephalogram, imaging, treatment and prognosis in epileptic nystagmus through reviewing literature. We found IEN occurs more frequently in children than in adults. Etiological factors included trauma, cerebral vascular disease, tumor, and anoxia. The frequency of IEN was high, which varied from several to hundreds of times per day, and the duration of it was usually less than 1 minute. EN and its subtypes, such as epileptic monocular nystagmus, vertical epileptic nystagmus, epileptic skew deviation, periodic alternating nystagmus, and partial oculo-clonic status, are rare. The fast phase of the nystagmus was contralateral to the epileptogenic zone in most cases. Periodic lateralized epileptiform discharges (PLEDs) is a distinct EEG pattern in EN. Our findings suggested that the occipital lobe may plays a key role in the origin of EN. PMID:26550287

  3. Toward Epileptic Brain Region Detection Based on Magnetic Nanoparticle Patterning

    PubMed Central

    Pedram, Maysam Z.; Shamloo, Amir; Alasty, Aria; Ghafar-Zadeh, Ebrahim

    2015-01-01

    Resection of the epilepsy foci is the best treatment for more than 15% of epileptic patients or 50% of patients who are refractory to all forms of medical treatment. Accurate mapping of the locations of epileptic neuronal networks can result in the complete resection of epileptic foci. Even though currently electroencephalography is the best technique for mapping the epileptic focus, it cannot define the boundary of epilepsy that accurately. Herein we put forward a new accurate brain mapping technique using superparamagnetic nanoparticles (SPMNs). The main hypothesis in this new approach is the creation of super-paramagnetic aggregates in the epileptic foci due to high electrical and magnetic activities. These aggregates may improve tissue contrast of magnetic resonance imaging (MRI) that results in improving the resection of epileptic foci. In this paper, we present the mathematical models before discussing the simulation results. Furthermore, we mimic the aggregation of SPMNs in a weak magnetic field using a low-cost microfabricated device. Based on these results, the SPMNs may play a crucial role in diagnostic epilepsy and the subsequent treatment of this disease. PMID:26402686

  4. Toward Epileptic Brain Region Detection Based on Magnetic Nanoparticle Patterning.

    PubMed

    Pedram, Maysam Z; Shamloo, Amir; Alasty, Aria; Ghafar-Zadeh, Ebrahim

    2015-01-01

    Resection of the epilepsy foci is the best treatment for more than 15% of epileptic patients or 50% of patients who are refractory to all forms of medical treatment. Accurate mapping of the locations of epileptic neuronal networks can result in the complete resection of epileptic foci. Even though currently electroencephalography is the best technique for mapping the epileptic focus, it cannot define the boundary of epilepsy that accurately. Herein we put forward a new accurate brain mapping technique using superparamagnetic nanoparticles (SPMNs). The main hypothesis in this new approach is the creation of super-paramagnetic aggregates in the epileptic foci due to high electrical and magnetic activities. These aggregates may improve tissue contrast of magnetic resonance imaging (MRI) that results in improving the resection of epileptic foci. In this paper, we present the mathematical models before discussing the simulation results. Furthermore, we mimic the aggregation of SPMNs in a weak magnetic field using a low-cost microfabricated device. Based on these results, the SPMNs may play a crucial role in diagnostic epilepsy and the subsequent treatment of this disease. PMID:26402686

  5. Stress Effects on the Hippocampus: A Critical Review

    ERIC Educational Resources Information Center

    Kim, Eun Joo; Pellman, Blake; Kim, Jeansok J.

    2015-01-01

    Uncontrollable stress has been recognized to influence the hippocampus at various levels of analysis. Behaviorally, human and animal studies have found that stress generally impairs various hippocampal-dependent memory tasks. Neurally, animal studies have revealed that stress alters ensuing synaptic plasticity and firing properties of hippocampal…

  6. Up-regulation of GABA transporters and GABA(A) receptor α1 subunit in tremor rat hippocampus.

    PubMed

    Mao, Xiaoyuan; Guo, Feng; Yu, Junling; Min, Dongyu; Wang, Zhanyou; Xie, Ni; Chen, Tianbao; Shaw, Chris; Cai, Jiqun

    2010-12-17

    The loss of GABAergic neurotransmission has been closely linked with epileptogenesis. The modulation of the synaptic activity occurs both via the removal of GABA from the synaptic cleft and by GABA transporters (GATs) and by modulation of GABA receptors. The tremor rat (TRM; tm/tm) is the parent strain of the spontaneously epileptic rat (SER; zi/zi, tm/tm), which exhibits absence-like seizure after 8 weeks of age. However, there are no reports that can elucidate the effects of GATs and GABA(A) receptors (GABARs) on TRMs. The present study was conducted to detect GATs and GABAR α1 subunit in TRMs hippocampus at mRNA and protein levels. In this study, total synaptosomal GABA content was significantly decreased in TRMs hippocampus compared with control Wistar rats by high performance liquid chromatography (HPLC); mRNA and protein expressions of GAT-1, GAT-3 and GABAR α1 subunit were all significantly increased in TRMs hippocampus by real time PCR and Western blot, respectively; GAT-1 and GABAR α1 subunit proteins were localized widely in TRMs and control rats hippocampus including CA1, CA3 and dentate gyrus (DG) regions whereas only a wide distribution of GAT-3 was observed in CA1 region by immunohistochemistry. These data demonstrate that excessive expressions of GAT-1 as well as GAT-3 and GABAR α1 subunit in TRMs hippocampus may provide the potential therapeutic targets for genetic epilepsy. PMID:20851161

  7. Centrophenoxine activates acetylcholinesterase activity in hippocampus of aged rats.

    PubMed

    Sharma, D; Singh, R

    1995-05-01

    Age-related changes in the acetylcholinesterase activity were measured in the hippocampus, brain stem and cerebellum of rats (aged 4, 8, 16 and 24 months). The age-dependent decrease in the enzyme activity first appeared in the hippocampus; the brain stem was affected later while the cerebellum remained unaffected. Centrophenoxine, usually considered as an ageing reversal drug and also regarded as a neuroenergeticum in human therapy, increased the acetylcholinesterase activity in the hippocampus of aged rats, the activity was also elevated in the brain stem but no in the cerebellum. The acetylcholinesterase-stimulating influence of the drug is likely to be implicated in the pharmacological reversal of the age related decline of the cholinergic system. This effect of the drug may also mediate its effects on cognitive and neuronal synaptic functions. PMID:7558197

  8. Newly generated neurons at 2 months post-status epilepticus are functionally integrated into neuronal circuitry in mouse hippocampus.

    PubMed

    Hu, Ming; Zhu, Kun; Chen, Xin-Lin; Zhang, Yao-Jie; Zhang, Jian-Shui; Xiao, Xin-Li; Liu, Jian-Xin; Liu, Yong

    2015-11-01

    Emerging evidence has linked chronic temporal lobe epilepsy to dramatically reduced neurogenesis in the dentate gyrus. However, the profile of different components of neurogenesis in the chronically epileptic hippocampus is still unclear, especially the incorporation of newly generated cells. To address the issue, newly generated cells in the sub-granular zone of the dentate gyrus were labeled by the proliferation marker bromodeoxyuridine (BrdU) or retroviral vector expressing green fluorescent protein 2 months after pilocarpine-induced status epilepticus. The newly generated neurons that extended axons to CA3 area or integrated into memory circuits were visualized by cholera toxin B subunit retrograde tracing, and detecting activation of BrdU(+) cells following a recall of spatial memory test at the chronic stage of TLE. We found that the microenvironment was still able to sustain significant neuronal differentiation of newly generated cells at 2 months post-status epilepticus time-point, and newly added neurons into granular cell layer were still able to integrate into neuronal circuitry, both anatomically and functionally. Quantified analyses of BrdU(+) or Ki-67(+) cells demonstrated that there was a reduced proliferation of progenitor cells and diminished survival of newly generated cells in the epileptic hippocampus. Both decreased levels of neurotrophic factors in the surrounding milieu and cell loss in the CA3 area might contribute the decreased production of new cells and their survival following chronic epilepsy. These results suggest that decreased neurogenesis in the chronically epileptic hippocampus 2 months post status epilepticus is not associated with altered integration of newly generated neurons, and that developing strategies to augment hippocampal neurogenesis in chronic epilepsy might be protective. PMID:26384773

  9. Emergence of semiology in epileptic seizures.

    PubMed

    Chauvel, Patrick; McGonigal, Aileen

    2014-09-01

    Semiology, the manifestation of epilepsy, is dependent upon electrical activity produced by epileptic seizures that are organized within existing neural pathways. Clinical signs evolve as the epileptic discharge spreads in both time and space. Studying the relation between these, of which the temporal component is at least as important as the spatial one, is possible using anatomo-electro-clinical correlations of stereoelectroencephalography (SEEG) data. The period of semiology production occurs with variable time lag after seizure onset and signs then emerge more or less rapidly depending on seizure type (temporal seizures generally propagating more slowly and frontal seizures more quickly). The subset of structures involved in semiological production, the "early spread network", is tightly linked to those constituting the epileptogenic zone. The level of complexity of semiological features varies according to the degree of involvement of the primary or associative cortex, with the former having a direct relation to peripheral sensory and motor systems with production of hallucinations (visual and auditory) or elementary sensorimotor signs. Depending on propagation pattern, these signs can occur in a "march" fashion as described by Jackson. On the other hand, seizures involving the associative cortex, having a less direct relation with the peripheral nervous system, and necessarily involving more widely distributed networks manifest with altered cognitive and/or behavioral signs whose neural substrate involves a network of cortical structures, as has been observed for normal cognitive processes. Other than the anatomical localization of these structures, the frequency of the discharge is a crucial determinant of semiological effect since a fast (gamma) discharge will tend to deactivate normal function, whereas a slower theta discharge can mimic physiological function. In terms of interaction between structures, the degree of synchronization plays a key role in

  10. Neural Representations of Location Outside the Hippocampus

    ERIC Educational Resources Information Center

    Knierim, James J.

    2006-01-01

    Place cells of the rat hippocampus are a dominant model system for understanding the role of the hippocampus in learning and memory at the level of single-unit and neural ensemble responses. A complete understanding of the information processing and computations performed by the hippocampus requires detailed knowledge about the properties of the…

  11. Mouse neuroblastoma cell based model and the effect of epileptic events on calcium oscillations and neural spikes

    NASA Astrophysics Data System (ADS)

    Kim, Suhwan; Baek, Juyeong; Jung, Unsang; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

    2013-05-01

    Recently, Mouse neuroblastoma cells are considered as an attractive model for the study of human neurological and prion diseases, and intensively used as a model system in different areas. Among those areas, differentiation of neuro2a (N2A) cells, receptor mediated ion current, and glutamate induced physiological response are actively investigated. The reason for the interest to mouse neuroblastoma N2A cells is that they have a fast growing rate than other cells in neural origin with a few another advantages. This study evaluated the calcium oscillations and neural spikes recording of mouse neuroblastoma N2A cells in an epileptic condition. Based on our observation of neural spikes in mouse N2A cell with our proposed imaging modality, we report that mouse neuroblastoma N2A cells can be an important model related to epileptic activity studies. It is concluded that the mouse neuroblastoma N2A cells produce the epileptic spikes in vitro in the same way as produced by the neurons or the astrocytes. This evidence advocates the increased and strong level of neurotransmitters release by enhancement in free calcium using the 4-aminopyridine which causes the mouse neuroblastoma N2A cells to produce the epileptic spikes and calcium oscillation.

  12. Mouse neuroblastoma cell-based model and the effect of epileptic events on calcium oscillations and neural spikes

    NASA Astrophysics Data System (ADS)

    Kim, Suhwan; Jung, Unsang; Baek, Juyoung; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

    2013-01-01

    Recently, mouse neuroblastoma cells have been considered as an attractive model for the study of human neurological and prion diseases, and they have been intensively used as a model system in different areas. For example, the differentiation of neuro2a (N2A) cells, receptor-mediated ion current, and glutamate-induced physiological responses have been actively investigated with these cells. These mouse neuroblastoma N2A cells are of interest because they grow faster than other cells of neural origin and have a number of other advantages. The calcium oscillations and neural spikes of mouse neuroblastoma N2A cells in epileptic conditions are evaluated. Based on our observations of neural spikes in these cells with our proposed imaging modality, we reported that they can be an important model in epileptic activity studies. We concluded that mouse neuroblastoma N2A cells produce epileptic spikes in vitro in the same way as those produced by neurons or astrocytes. This evidence suggests that increased levels of neurotransmitter release due to the enhancement of free calcium from 4-aminopyridine causes the mouse neuroblastoma N2A cells to produce epileptic spikes and calcium oscillations.

  13. De novo mutations in the classic epileptic encephalopathies

    PubMed Central

    2013-01-01

    Epileptic encephalopathies (EE) are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here, we report a screen for de novo mutations in patients with two classical EE: infantile spasms (IS, n=149) and Lennox-Gastaut Syndrome (LGS, n=115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ~4,000 genes that are the most intolerant to functional genetic variation in the human population (p=2.9 × 10−3). Among these are GABRB3 with de novo mutations in four patients and ALG13 with the same de novo mutation in two patients; both genes show clear statistical evidence of association. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are p=4.1 × 10−10 and p=7.8 × 10−12, respectively. Other genes with de novo mutations in this cohort include: CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HDAC4, HNRNPU, IQSEC2, MTOR, and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the Fragile X protein (p<10−8), as was reported for autism spectrum disorders (ASD)1. PMID:23934111

  14. Simultaneous fMRI and local field potential measurements during epileptic seizures in medetomidine sedated rats using RASER pulse sequence

    PubMed Central

    Airaksinen, Antti M; Niskanen, Juha-Pekka; Chamberlain, Ryan; Huttunen, Joanna K; Nissinen, Jari; Garwood, Michael; Pitkänen, Asla; Gröhn, Olli

    2010-01-01

    Simultaneous electrophysiological and functional magnetic resonance imaging (fMRI) measurements of animal models of epilepsy are methodologically challenging, but essential to better understand abnormal brain activity and hemodynamics during seizures. In the present study, fMRI of medetomidine sedated rats was performed using novel Rapid Acquisition by Sequential Excitation and Refocusing (RASER) fast imaging pulse sequence and simultaneous local field potential (LFP) measurements during kainic acid (KA) induced seizures. The image distortion caused by the hippocampal measuring electrode was clearly seen in echo planar imaging (EPI) images, whereas no artifact was seen in RASER images. Robust blood oxygenation level dependent (BOLD) responses were observed in the hippocampus during KA induced seizures. The recurrent epileptic seizures were detected in the LFP signal after KA injection. The presented combination of deep electrode LFP measurements and fMRI under medetomidine anesthesia, that does not significantly suppress KA induced seizures, provides a unique tool for studying abnormal brain activity in rats. PMID:20725933

  15. Asynchronous electrical activity in epileptic seizures

    NASA Astrophysics Data System (ADS)

    Holman, Katherine; Lim, Eugene; Gliske, Stephen; Stacey, William; Fink, Christian

    High-frequency oscillations (HFOs) have been postulated to be potential biomarkers for focal epileptic seizures, with fast ripples (>250 Hz) as the most interesting candidate. The mechanisms underlying the generation of fast ripples, however, are not well understood. In this study, we draw upon results from previous computational studies on HFOs to develop a new mathematical model from first principles describing the generation of HFOs through asynchronous neuronal firing. Asynchrony in the model is obtained with the introduction of two parameters of heterogeneity: variability in the inter-spike interval (ISI) and jitter. The model predicts the generation of harmonic narrow-band oscillations if the heterogeneity-governing parameters do not differ from the predefined ISI by more than 20%. Comparisons against results from a separately constructed computational model verify the accuracy of the model in study. These results provide us with a rigorous framework in which we may investigate the mechanisms driving the generation of abnormal HFOs, and may serve as groundwork for future research in epileptogenesis. Nsf Grant 1003992, Ohio Wesleyan University SSRP.

  16. Cerebrospinal fluid findings after epileptic seizures.

    PubMed

    Chatzikonstantinou, Anastasios; Ebert, Anne D; Hennerici, Michael G

    2015-12-01

    We aimed to evaluate ictally-induced CSF parameter changes after seizures in adult patients without acute inflammatory diseases or infectious diseases associated with the central nervous system. In total, 151 patients were included in the study. All patients were admitted to our department of neurology following acute seizures and received an extensive work-up including EEG, cerebral imaging, and CSF examinations. CSF protein elevation was found in most patients (92; 60.9%) and was significantly associated with older age, male sex, and generalized seizures. Abnormal CSF-to-serum glucose ratio was found in only nine patients (5.9%) and did not show any significant associations. CSF lactate was elevated in 34 patients (22.5%) and showed a significant association with focal seizures with impaired consciousness, status epilepticus, the presence of EEG abnormalities in general and epileptiform potentials in particular, as well as epileptogenic lesions on cerebral imaging. Our results indicate that non-inflammatory CSF elevation of protein and lactate after epileptic seizures is relatively common, in contrast to changes in CSF-to-serum glucose ratio, and further suggest that these changes are caused by ictal activity and are related to seizure type and intensity. We found no indication that these changes may have further-reaching pathological implications besides their postictal character. PMID:26575850

  17. Disposition of sodium valproate in epileptic patients.

    PubMed Central

    Perucca, E; Gatti, G; Frigo, G M; Crema, A; Calzetti, S; Visintini, D

    1978-01-01

    1 Serum levels of valproic acid have been determined at fixed intervals after the administration of single oral and intravenous doses (800 mg) to six epileptic patients receiving chronic treatment with other antiepileptic drugs. 2 Serum levels declined monoexponentially shortly after the intravenous administration. Biological half-lives averaged 9.0 +/- 1.4 h (s.d.). Volumes of distribution were 0.175 +/- 0.025 l/kg. There was a statistically significant negative correlation between volumes of distribution and serum half-lives (P less than 0.005). 3 After oral doses serum levels rose rapidly to peak values within 0.5--2 h. Biological availability was 96 +/- 9%. 4 Comparison with a previous study performed according to the same protocol in healthy volunteers showed significantly increased volumes of distribution and rates of elimination in the patients. Total serum clearance was 85% higher in the patients as compared to the healthy subjects (P less than 0.001). Possible explanations for these findings are discussed. PMID:350251

  18. Altered regional homogeneity in epileptic patients with infantile spasm: A resting-state fMRI study.

    PubMed

    Tan, Zhen; Li, Yongxin; Zang, Dongdong; Zhang, Heye; Zhao, Cailei; Jiang, Haibo; Chen, Yan; Cao, Dezhi; Chen, Li; Liao, Jianxiang; Chen, Qian; Luan, Guoming

    2016-01-01

    Infantile spasm (IS) syndrome is an age-related epileptic encephalopathy that occurs in children. The purpose of this study was to investigate regional homogeneity (ReHo) changes in IS patients. Resting-state fMRI was performed on 11 patients with IS, along with 35 age- and sex-matched healthy subjects. Group comparisons between the two groups demonstrate that the pattern of regional synchronization synchronization in IS patients is changed. Decreased ReHo values were found in default mode network, bilateral motor-related areas and left occipital gyrus of the patient group. Increased ReHo was found in regions of cingulum, cerebellum, supplementary motor area and brain deep nucleus, such as hippocampus, caudate, thalamus and insula. The significant differences might indicate that epileptic action have some injurious effects on the motor, executive and cognitive related regions. In addition, ReHo values of left precuneus and right superior frontal gyrus were associated with the epilepsy duration in the IS group. The correlation results indicate that the involvement of these regions may be related to the seizure generation. Our results suggest that IS may have an injurious effect on the brain activation. The findings may shed new light on the understanding the neural mechanism of IS epilepsy. PMID:27002912

  19. Regionally specific expression of high-voltage-activated calcium channels in thalamic nuclei of epileptic and non-epileptic rats.

    PubMed

    Kanyshkova, Tatyana; Ehling, Petra; Cerina, Manuela; Meuth, Patrick; Zobeiri, Mehrnoush; Meuth, Sven G; Pape, Hans-Christian; Budde, Thomas

    2014-07-01

    The polygenic origin of generalized absence epilepsy results in dysfunction of ion channels that allows the switch from physiological asynchronous to pathophysiological highly synchronous network activity. Evidence from rat and mouse models of absence epilepsy indicates that altered Ca(2+) channel activity contributes to cellular and network alterations that lead to seizure activity. Under physiological circumstances, high voltage-activated (HVA) Ca(2+) channels are important in determining the thalamic firing profile. Here, we investigated a possible contribution of HVA channels to the epileptic phenotype using a rodent genetic model of absence epilepsy. In this study, HVA Ca(2+) currents were recorded from neurons of three different thalamic nuclei that are involved in both sensory signal transmission and rhythmic-synchronized activity during epileptic spike-and-wave discharges (SWD), namely the dorsal part of the lateral geniculate nucleus (dLGN), the ventrobasal thalamic complex (VB) and the reticular thalamic nucleus (NRT) of epileptic Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) and non-epileptic August Copenhagen Irish (ACI) rats. HVA Ca(2+) current densities in dLGN neurons were significantly increased in epileptic rats compared with non-epileptic controls while other thalamic regions revealed no differences between the strains. Application of specific channel blockers revealed that the increased current was carried by L-type Ca(2+) channels. Electrophysiological evidence of increased L-type current correlated with up-regulated mRNA and protein expression of a particular L-type channel, namely Cav1.3, in dLGN of epileptic rats. No significant changes were found for other HVA Ca(2+) channels. Moreover, pharmacological inactivation of L-type Ca(2+) channels results in altered firing profiles of thalamocortical relay (TC) neurons from non-epileptic rather than from epileptic rats. While HVA Ca(2+) channels influence tonic and burst firing in ACI and WAG

  20. Measuring resetting of brain dynamics at epileptic seizures: application of global optimization and spatial synchronization techniques.

    PubMed

    Sabesan, Shivkumar; Chakravarthy, Niranjan; Tsakalis, Kostas; Pardalos, Panos; Iasemidis, Leon

    2009-01-01

    Epileptic seizures are manifestations of intermittent spatiotemporal transitions of the human brain from chaos to order. Measures of chaos, namely maximum Lyapunov exponents (STL(max)), from dynamical analysis of the electroencephalograms (EEGs) at critical sites of the epileptic brain, progressively converge (diverge) before (after) epileptic seizures, a phenomenon that has been called dynamical synchronization (desynchronization). This dynamical synchronization/desynchronization has already constituted the basis for the design and development of systems for long-term (tens of minutes), on-line, prospective prediction of epileptic seizures. Also, the criterion for the changes in the time constants of the observed synchronization/desynchronization at seizure points has been used to show resetting of the epileptic brain in patients with temporal lobe epilepsy (TLE), a phenomenon that implicates a possible homeostatic role for the seizures themselves to restore normal brain activity. In this paper, we introduce a new criterion to measure this resetting that utilizes changes in the level of observed synchronization/desynchronization. We compare this criterion's sensitivity of resetting with the old one based on the time constants of the observed synchronization/desynchronization. Next, we test the robustness of the resetting phenomena in terms of the utilized measures of EEG dynamics by a comparative study involving STL(max), a measure of phase (ϕ(max)) and a measure of energy (E) using both criteria (i.e. the level and time constants of the observed synchronization/desynchronization). The measures are estimated from intracranial electroencephalographic (iEEG) recordings with subdural and depth electrodes from two patients with focal temporal lobe epilepsy and a total of 43 seizures. Techniques from optimization theory, in particular quadratic bivalent programming, are applied to optimize the performance of the three measures in detecting preictal entrainment. It is

  1. Plic-1, a new target in repressing epileptic seizure by regulation of GABAAR function in patients and a rat model of epilepsy.

    PubMed

    Zhang, Yujiao; Li, Zengyou; Gu, Juan; Zhang, Yanke; Wang, Wei; Shen, Hui; Chen, Guojun; Wang, Xuefeng

    2015-12-01

    Dysfunction of γ-aminobutyric acid A (GABAA) receptors (GABAARs) is a prominent factor affecting intractable epilepsy. Plic-1, an ubiquitin-like protein enriched in the inhibitory synapses connecting GABAARs and the ubiquitin protease system (UPS), plays a key role in the modification of GABAAR functions. However, the relationship between Plic-1 and epileptogenesis is not known. In the present study, we aimed to investigate Plic-1 levels in patients with temporal lobe epilepsy, as well as the role of Plic-1 in regulating onset and progression of epilepsy in animal models. We found that Plic-1 expression was significantly decreased in patients with epilepsy as well as pilocarpine- and pentylenetetrazol (PTZ)-induced rat epileptic models. Intrahippocampal injection of the PePα peptide, which disrupts Plic-1 binding to GABAARs, significantly shortened the latency of seizure onset, and increased the seizure severity and duration in these two epileptic models. Overexpressed Plic-1 through lentivirus transfection into a PTZ model resulted in a reduction in both seizure severity and generalized tonic-clonic seizure duration. Whole-cell clamp recordings revealed that the PePα peptide decreased miniature inhibitory postsynaptic currents (mIPSCs) whereas overexpressed Plic-1 increased mIPSCs in the pyramidal neurons of the hippocampus. These effects can be blocked by picrotoxin, a GABAAR inhibitor. Our results indicate that Plic-1 plays an important role in managing epileptic seizures by enhancing seizure inhibition through regulation of GABAARs at synaptic sites. PMID:26415648

  2. A Novel Dynamic Update Framework for Epileptic Seizure Prediction

    PubMed Central

    Wang, Minghui; Hong, Xiaojun; Han, Jie

    2014-01-01

    Epileptic seizure prediction is a difficult problem in clinical applications, and it has the potential to significantly improve the patients' daily lives whose seizures cannot be controlled by either drugs or surgery. However, most current studies of epileptic seizure prediction focus on high sensitivity and low false-positive rate only and lack the flexibility for a variety of epileptic seizures and patients' physical conditions. Therefore, a novel dynamic update framework for epileptic seizure prediction is proposed in this paper. In this framework, two basic sample pools are constructed and updated dynamically. Furthermore, the prediction model can be updated to be the most appropriate one for the prediction of seizures' arrival. Mahalanobis distance is introduced in this part to solve the problem of side information, measuring the distance between two data sets. In addition, a multichannel feature extraction method based on Hilbert-Huang transform and extreme learning machine is utilized to extract the features of a patient's preseizure state against the normal state. At last, a dynamic update epileptic seizure prediction system is built up. Simulations on Freiburg database show that the proposed system has a better performance than the one without update. The research of this paper is significantly helpful for clinical applications, especially for the exploitation of online portable devices. PMID:25050381

  3. A novel dynamic update framework for epileptic seizure prediction.

    PubMed

    Han, Min; Ge, Sunan; Wang, Minghui; Hong, Xiaojun; Han, Jie

    2014-01-01

    Epileptic seizure prediction is a difficult problem in clinical applications, and it has the potential to significantly improve the patients' daily lives whose seizures cannot be controlled by either drugs or surgery. However, most current studies of epileptic seizure prediction focus on high sensitivity and low false-positive rate only and lack the flexibility for a variety of epileptic seizures and patients' physical conditions. Therefore, a novel dynamic update framework for epileptic seizure prediction is proposed in this paper. In this framework, two basic sample pools are constructed and updated dynamically. Furthermore, the prediction model can be updated to be the most appropriate one for the prediction of seizures' arrival. Mahalanobis distance is introduced in this part to solve the problem of side information, measuring the distance between two data sets. In addition, a multichannel feature extraction method based on Hilbert-Huang transform and extreme learning machine is utilized to extract the features of a patient's preseizure state against the normal state. At last, a dynamic update epileptic seizure prediction system is built up. Simulations on Freiburg database show that the proposed system has a better performance than the one without update. The research of this paper is significantly helpful for clinical applications, especially for the exploitation of online portable devices. PMID:25050381

  4. [Non-epileptic motor paroxysmal phenomena in wakefulness in childhood].

    PubMed

    Ruggieri, Víctor L; Arberas, Claudia L

    2013-09-01

    Paroxysmal events in childhood are a challenge for pediatric neurologists, given its highly heterogeneous clinical manifestations, often difficult to distinguish between phenomena of epileptic seizure or not. The non-epileptic paroxysmal episodes are neurological phenomena, with motor, sensory symptoms, and/or sensory impairments, with or without involvement of consciousness, epileptic phenomena unrelated, so no electroencephalographic correlative expression between or during episodes. From the clinical point of view can be classified into four groups: motor phenomena, syncope, migraine (and associated conditions) and acute psychiatric symptoms. In this paper we analyze paroxysmal motor phenomena in awake children, dividing them according to their clinical manifestations: extrapyramidal episodes (paroxysmal kinesiogenic, non kinesiogenic and not related to exercise dyskinesias, Dopa responsive dystonia) and similar symptoms of dystonia (Sandifer syndrome); manifestations of startle (hyperekplexia); episodic eye and head movements (benign paroxysmal tonic upward gaze nistagmus deviation); episodic ataxia (familial episodic ataxias, paroxysmal benign vertigo); stereotyped and phenomena of self-gratification; and myoclonic events (benign myoclonus of early infancy). The detection of these syndromes will, in many cases, allow an adequate genetic counseling, initiate a specific treatment and avoid unnecessary additional studies. Molecular studies have demonstrated a real relationship between epileptic and non-epileptic basis of many of these entities and surely the identification of the molecular basis and understanding of the pathophysiological mechanisms in many of them allow us, in the near future will benefit our patients. PMID:23897137

  5. Hippocampus is place of interaction between unconscious and conscious memories.

    PubMed

    Züst, Marc Alain; Colella, Patrizio; Reber, Thomas Peter; Vuilleumier, Patrik; Hauf, Martinus; Ruch, Simon; Henke, Katharina

    2015-01-01

    Recent evidence suggests that humans can form and later retrieve new semantic relations unconsciously by way of hippocampus-the key structure also recruited for conscious relational (episodic) memory. If the hippocampus subserves both conscious and unconscious relational encoding/retrieval, one would expect the hippocampus to be place of unconscious-conscious interactions during memory retrieval. We tested this hypothesis in an fMRI experiment probing the interaction between the unconscious and conscious retrieval of face-associated information. For the establishment of unconscious relational memories, we presented subliminal (masked) combinations of unfamiliar faces and written occupations ("actor" or "politician"). At test, we presented the former subliminal faces, but now supraliminally, as cues for the reactivation of the unconsciously associated occupations. We hypothesized that unconscious reactivation of the associated occupation-actor or politician-would facilitate or inhibit the subsequent conscious retrieval of a celebrity's occupation, which was also actor or politician. Depending on whether the reactivated unconscious occupation was congruent or incongruent to the celebrity's occupation, we expected either quicker or delayed conscious retrieval process. Conscious retrieval was quicker in the congruent relative to a neutral baseline condition but not delayed in the incongruent condition. fMRI data collected during subliminal face-occupation encoding confirmed previous evidence that the hippocampus was interacting with neocortical storage sites of semantic knowledge to support relational encoding. fMRI data collected at test revealed that the facilitated conscious retrieval was paralleled by deactivations in the hippocampus and neocortical storage sites of semantic knowledge. We assume that the unconscious reactivation has pre-activated overlapping relational representations in the hippocampus reducing the neural effort for conscious retrieval. This

  6. Block term decomposition for modelling epileptic seizures

    NASA Astrophysics Data System (ADS)

    Hunyadi, Borbála; Camps, Daan; Sorber, Laurent; Paesschen, Wim Van; Vos, Maarten De; Huffel, Sabine Van; Lathauwer, Lieven De

    2014-12-01

    Recordings of neural activity, such as EEG, are an inherent mixture of different ongoing brain processes as well as artefacts and are typically characterised by low signal-to-noise ratio. Moreover, EEG datasets are often inherently multidimensional, comprising information in time, along different channels, subjects, trials, etc. Additional information may be conveyed by expanding the signal into even more dimensions, e.g. incorporating spectral features applying wavelet transform. The underlying sources might show differences in each of these modes. Therefore, tensor-based blind source separation techniques which can extract the sources of interest from such multiway arrays, simultaneously exploiting the signal characteristics in all dimensions, have gained increasing interest. Canonical polyadic decomposition (CPD) has been successfully used to extract epileptic seizure activity from wavelet-transformed EEG data (Bioinformatics 23(13):i10-i18, 2007; NeuroImage 37:844-854, 2007), where each source is described by a rank-1 tensor, i.e. by the combination of one particular temporal, spectral and spatial signature. However, in certain scenarios, where the seizure pattern is nonstationary, such a trilinear signal model is insufficient. Here, we present the application of a recently introduced technique, called block term decomposition (BTD) to separate EEG tensors into rank- ( L r , L r ,1) terms, allowing to model more variability in the data than what would be possible with CPD. In a simulation study, we investigate the robustness of BTD against noise and different choices of model parameters. Furthermore, we show various real EEG recordings where BTD outperforms CPD in capturing complex seizure characteristics.

  7. New avenues for anti-epileptic drug discovery and development.

    PubMed

    Löscher, Wolfgang; Klitgaard, Henrik; Twyman, Roy E; Schmidt, Dieter

    2013-10-01

    Despite the introduction of over 15 third-generation anti-epileptic drugs, current medications fail to control seizures in 20-30% of patients. However, our understanding of the mechanisms mediating the development of epilepsy and the causes of drug resistance has grown substantially over the past decade, providing opportunities for the discovery and development of more efficacious anti-epileptic and anti-epileptogenic drugs. In this Review we discuss how previous preclinical models and clinical trial designs may have hampered the discovery of better treatments. We propose that future anti-epileptic drug development may be improved through a new joint endeavour between academia and the industry, through the identification and application of tools for new target-driven approaches, and through comparative preclinical proof-of-concept studies and innovative clinical trials designs. PMID:24052047

  8. Complementary treatment of psychotic and epileptic patients in malaysia.

    PubMed

    Razali, Salleh Mohd; Yassin, Azhar Mohd

    2008-09-01

    The objective of this article is to describe and compare the use of traditional/complementary medicine (T/CM) among psychotic (schizophrenia and schizophreniform disorder) and epileptic Malay patients in peninsular Malaysia. There were 60 patients in each group. T/CM consultation was uniformly spread across all levels of education and social status. We could not find a single over-riding factor that influenced the decision to seek T/CM treatment because the decision to seek such treatment was complex and the majority of decisions were made by others. Fifty-three patients (44.2%), consisting of 37 (61.7%) psychotic and 16 (26.7%) epileptic patients had consulted Malay traditional healers (bomoh) and/or homeopathic practitioners in addition to modern treatment; of these, only three had consulted bomoh and homeopathic practitioners at the same time. The use of T/CM was significantly higher in psychotic than in epileptic Malay patients. PMID:18799643

  9. Acute transient deafness representing a negative epileptic phenomenon.

    PubMed

    Shahar, Eli; Ravid, Sarit; Genizi, Jacob; Schif, Aharon

    2010-07-01

    We report herein 2 children who presented with acute deafness heralding an epileptic event manifesting thereafter by loss of consciousness and tonic generalized posturing, possibly reflecting a negative epileptic phenomenon. The first previously healthy male had 2 paroxysmal episodes 7 months apart, starting with acute deafness lasting for a few minutes followed by loss of consciousness and generalized tonic posturing for 10 minutes. Electroencephalography (EEG) during the second episodes demonstrated generalized epileptiform discharges. The second with previously controlled partial complex seizures presented with episodes of complete deafness lasting for a few minutes followed by loss of consciousness and focal tonic posturing lasting 10 minutes. Such acute deafness represented an aura of a focal seizure substantiated by right focal temporal epileptic discharges within the region of the primary auditory cortex. Therefore, EEG should be performed in any case of acute transient deafness, even in the absence of accompanying overt clinical seizures. PMID:20042694

  10. Automatic classification of penicillin-induced epileptic EEG spikes.

    PubMed

    Kortelainen, Jukka; Silfverhuth, Minna; Suominen, Kalervo; Sonkajarvi, Eila; Alahuhta, Seppo; Jantti, Ville; Seppanen, Tapio

    2010-01-01

    Penicillin-induced focal epilepsy is a well-known model in epilepsy research. In this model, epileptic activity is generated by delivering penicillin focally to the cortex. The drug induces interictal electroencephalographic (EEG) spikes which evolve in time and may later change to ictal discharges. This paper proposes a method for automatic classification of these interictal epileptic spikes using iterative K-means clustering. The method is shown to be able to detect different spike waveforms and describe their characteristic occurrence in time during penicillin-induced focal epilepsy. The study offers potential for future research by providing a method to objectively and quantitatively analyze the time sequence of interictal epileptic activity. PMID:21096740

  11. Quality of life in epileptic patients compared with healthy people

    PubMed Central

    Gholami, Ali; Salarilak, Shaker; Lotfabadi, Pegah; Kiani, Fereshte; Rajabi, Abdolhalim; Mansori, Kamyar; Moosavi Jahromi, Zahra

    2016-01-01

    Background: Epilepsy is a common chronic neurological disorder that has a great impact on people’s lives. Patients with epilepsy are at increased risk for poor Quality of Life (QoL). The objective of this study was to evaluate the QoL of epileptic patients in comparison to healthy persons. Methods: This cross-sectional study was conducted on 52 epileptic patients from Golbu region in Neyshabur (a city in northeast of Iran). Using Short Form Health Survey (SF-36) scale, the data were collected between April and Jun 2012. Every patient were compared with two healthy persons. Epileptic and healthy persons were similar for age, sex and local residence. Pearson’s correlation coefficient and t-independent test applied for data analysis through SPSS v. 16 software. Results: Of 52 epileptic patients, 24 were female (46.2%) and 28 were male (53.8%). The mean±SD age of epileptic patients was 40.92±20.33yr (Rang: 15-86yr). The total mean score of SF- 36 in patient group was 55.88 and in healthy group 68.52and this difference was statistically significant (p<0.001). Among the different subscales of SF-36 in epileptic patients, the highest and the lowest mean scores were found for social functioning and general health subscales, respectively. The mean scores in patient group in comparison to healthy group were lower in all subscales of SF-36 and these differences were statistically significant in all domains (except role limitations due to physical problems domain and role limitations due to emotional problems domain). Conclusion: The study showed that epilepsy disease has an important role in QoL of patients, thus some interventional programs are necessary to improve their QOL. PMID:27493932

  12. Electroencephalogram of Age-Dependent Epileptic Encephalopathies in Infancy and Early Childhood

    PubMed Central

    Wong-Kisiel, Lily C.; Nickels, Katherine

    2013-01-01

    Epileptic encephalopathy syndromes are disorders in which the epileptiform abnormalities are thought to contribute to a progressive cerebral dysfunction. Characteristic electroencephalogram findings have an important diagnostic value in classification of epileptic encephalopathy syndromes. In this paper, we focus on electroencephalogram findings of childhood epileptic encephalopathy syndromes and provide sample illustrations. PMID:24024028

  13. De novo mutations in HCN1 cause early infantile epileptic encephalopathy.

    PubMed

    Nava, Caroline; Dalle, Carine; Rastetter, Agnès; Striano, Pasquale; de Kovel, Carolien G F; Nabbout, Rima; Cancès, Claude; Ville, Dorothée; Brilstra, Eva H; Gobbi, Giuseppe; Raffo, Emmanuel; Bouteiller, Delphine; Marie, Yannick; Trouillard, Oriane; Robbiano, Angela; Keren, Boris; Agher, Dahbia; Roze, Emmanuel; Lesage, Suzanne; Nicolas, Aude; Brice, Alexis; Baulac, Michel; Vogt, Cornelia; El Hajj, Nady; Schneider, Eberhard; Suls, Arvid; Weckhuysen, Sarah; Gormley, Padhraig; Lehesjoki, Anna-Elina; De Jonghe, Peter; Helbig, Ingo; Baulac, Stéphanie; Zara, Federico; Koeleman, Bobby P C; Haaf, Thomas; LeGuern, Eric; Depienne, Christel

    2014-06-01

    Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino acid substitutions. Patch-clamp recordings of Ih currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable early-onset epileptic encephalopathy in humans. PMID:24747641

  14. [Clinical approach to the first epileptic crisis in adults].

    PubMed

    Espinosa-Jovel, Camilo Alfonso; Sobrino-Mejía, Fidel Ernesto

    2014-04-16

    Seizures are one of the main reasons for visits to emergency and neurology. Represent a traumatic event with potential medical and social consequences. A first epileptic seizure, can be the initial manifestation of malignancy, systemic disorder or infection, but can also be the first manifestation of epilepsy. The misdiagnosis of symptomatic seizures and unprovoked seizure, significantly affects prognosis and patient outcomes. The aim of this review is to examine the general concepts that enable successful diagnostic and therapeutic approach to the patient presenting with a first epileptic seizure. PMID:24723179

  15. [Cortical dysgenesis with epileptic syndromes and symptomatic epilepsy in children].

    PubMed

    Milovanova, O A

    2015-01-01

    Cortical dysgenesis (CD) is a frequent inherited brain malformation. CD is a key cause of epileptic syndrome in children. In this review, the author presents a current classification of CD, etiological factors of their development, including gene mutations and adverse effects of various toxins and perinatal factors. A spectrum of clinical symptoms of CD with epileptic seizures is discussed in details. A role of current MRI-regimes in the diagnosis, the management of patients and prognosis of the course of CD are highlighted. PMID:26978511

  16. Uncommon t12 burst fracture after an epileptic crisis.

    PubMed

    Alian, Akiki

    2011-01-01

    People having an epileptic crisis present to the hospital with an altered mental status and generalised fatigue. The most common orthopaedic pathology associated to epilepsy is the undiagnosed posterior shoulder dislocation. These same patients often complain from back pain that is often neglected and misdiagnosed as muscular contracture following the epilepsy crisis. We describe here the case of a patient who presented after here epilepsy crisis with back pain. Investigations revealed an uncommon burst fracture that needed a surgical treatment. Conclusion. Back pain after an epileptic crisis should be investigated more seriously with an adequate clinical examination and a minimum of a radiography of the back. PMID:23198223

  17. Uncommon T12 Burst Fracture after an Epileptic Crisis

    PubMed Central

    Alian, Akiki

    2011-01-01

    People having an epileptic crisis present to the hospital with an altered mental status and generalised fatigue. The most common orthopaedic pathology associated to epilepsy is the undiagnosed posterior shoulder dislocation. These same patients often complain from back pain that is often neglected and misdiagnosed as muscular contracture following the epilepsy crisis. We describe here the case of a patient who presented after here epilepsy crisis with back pain. Investigations revealed an uncommon burst fracture that needed a surgical treatment. Conclusion. Back pain after an epileptic crisis should be investigated more seriously with an adequate clinical examination and a minimum of a radiography of the back. PMID:23198223

  18. A new approach towards predictability of epileptic seizures: KLT dimension.

    PubMed

    Venugopal, Rajeshkumar; Narayanan, K; Prasad, Awadhesh; Spanias, A; Sackellares, J C; Iasemidis, L D

    2003-01-01

    This paper proposes a measure of complexity of the epileptic electroencephalogram (EEG) based on the dimensionality of the Karhunen-Loeve Transform (KLT) in the time domain. We estimate the KLT dimensionality by assuming the same observation noise level in the EEG during the interictal period (between the seizures) as the one during an epileptic seizure (ictal period). Utilizing an optimality criterion based on the T-index [1] and the predictability time, derived from the created KLT dimensionality profiles, we show that 10 out of 15 seizures in one patient with temporal lobe epilepsy were predictable with an average predictability time of about 36 minutes. PMID:12724880

  19. Transient epileptic amnesia--a clinical update and a reformulation.

    PubMed Central

    Kapur, N

    1993-01-01

    While absence attacks and complex partial seizures have been well documented in patients with epilepsy, the delineation of pure episodes of memory loss without additional clinical manifestations remains poorly characterised. The recently described condition of transient epileptic amnesia (TEA) is critically examined, and four new cases are described, in each of which there were episodes of pure memory loss which subsequently proved to be epileptic in origin. The anatomical and pathophysiological basis of TEA is presumed to be similar to transient global amnesia (TGA), that is, it is likely to be primarily hippocampal in origin, but with more variable involvement of limbic and adjacent temporal lobe neocortical structures. PMID:8229029

  20. Adaptive time-frequency parametrization of epileptic spikes

    NASA Astrophysics Data System (ADS)

    Durka, Piotr J.

    2004-05-01

    Adaptive time-frequency approximations of signals have proven to be a valuable tool in electroencephalogram (EEG) analysis and research, where it is believed that oscillatory phenomena play a crucial role in the brain’s information processing. This paper extends this paradigm to the nonoscillating structures such as the epileptic EEG spikes, and presents the advantages of their parametrization in general terms such as amplitude and half-width. A simple detector of epileptic spikes in the space of these parameters, tested on a limited data set, gives very promising results. It also provides a direct distinction between randomly occurring spikes or spike/wave complexes and rhythmic discharges.

  1. Capparis ovata modulates brain oxidative toxicity and epileptic seizures in pentylentetrazol-induced epileptic rats.

    PubMed

    Nazıroğlu, Mustafa; Akay, Mehmet Berk; Çelik, Ömer; Yıldırım, Muhammed İkbal; Balcı, Erdinç; Yürekli, Vedat Ali

    2013-04-01

    It has been widely suggested that oxidative stress products play an important role in the pathophysiology of epilepsy. Capparis ovata (C. ovata) may useful treatment of epilepsy because it contains antioxidant flavonoids. The current study was designed to determine the effects of C. ovata on lipid peroxidation, antioxidant levels and electroencephalography (EEG) records in pentylentetrazol (PTZ)-induced epileptic rats. Thirty-two rats were randomly divided into four groups. First group was used as control although second group was PTZ group. Oral 100 and 200 mg/kg C. ovata were given to rats constituting the third and fourth groups for 7 days before PTZ administration. Second, third and forth groups received 60 mg/kg PTZ for induction of epilepsy. Three hours after administration of PTZ, EEG records, brain cortex and blood samples were taken all groups. The lipid peroxidation levels of the brain cortex, number of spikes and epileptiform discharges of EEG were higher in PTZ group than in control and C. ovata group whereas they were decreased by C. ovata administration. Vitamin A, vitamin C, vitamin E and β-carotene concentrations of brain cortex and latency to first spike of EEG were decreased by the PTZ administration although the brain cortex and plasma vitamin concentrations, and brain cortex and erythrocyte glutathione and glutathione peroxidase values were increased in PTZ + 100 and PTZ + 200 mg C. ovata groups. In conclusion, C. ovata administration caused protection against the PTZ-induced brain oxidative toxicity by inhibiting free radical and epileptic seizures, and supporting antioxidant redox system. PMID:23389657

  2. Comparison of automated and manual segmentation of hippocampus MR images

    NASA Astrophysics Data System (ADS)

    Haller, John W.; Christensen, Gary E.; Miller, Michael I.; Joshi, Sarang C.; Gado, Mokhtar; Csernansky, John G.; Vannier, Michael W.

    1995-05-01

    The precision and accuracy of area estimates from magnetic resonance (MR) brain images and using manual and automated segmentation methods are determined. Areas of the human hippocampus were measured to compare a new automatic method of segmentation with regions of interest drawn by an expert. MR images of nine normal subjects and nine schizophrenic patients were acquired with a 1.5-T unit (Siemens Medical Systems, Inc., Iselin, New Jersey). From each individual MPRAGE 3D volume image a single comparable 2-D slice (matrix equals 256 X 256) was chosen which corresponds to the same coronal slice of the hippocampus. The hippocampus was first manually segmented, then segmented using high dimensional transformations of a digital brain atlas to individual brain MR images. The repeatability of a trained rater was assessed by comparing two measurements from each individual subject. Variability was also compared within and between subject groups of schizophrenics and normal subjects. Finally, the precision and accuracy of automated segmentation of hippocampal areas were determined by comparing automated measurements to manual segmentation measurements made by the trained rater on MR and brain slice images. The results demonstrate the high repeatability of area measurement from MR images of the human hippocampus. Automated segmentation using high dimensional transformations from a digital brain atlas provides repeatability superior to that of manual segmentation. Furthermore, the validity of automated measurements was demonstrated by a high correlation with manual segmentation measurements made by a trained rater. Quantitative morphometry of brain substructures (e.g. hippocampus) is feasible by use of a high dimensional transformation of a digital brain atlas to an individual MR image. This method automates the search for neuromorphological correlates of schizophrenia by a new mathematically robust method with unprecedented sensitivity to small local and regional differences.

  3. Influences of "spasmolytic powder" on pgp expression of Coriaria Lactone-kindling drug-resistant epileptic rat model.

    PubMed

    Chen, Lei; Feng, Peimin; Li, Yaohua; Zhou, Dong

    2013-09-01

    The earliest records of traditional Chinese medicine (TCM) prevention and treatment of epilepsy dated back to famous "Huang Di Nei Jing." TCM "spasmolytic powder" (equal-ratio compatibility of scorpion and centipede) is a famous prescription which was recognized as a useful add-on drug for refractory epilepsy in clinical observations. Multidrug resistance gene (mdr1) product Pgp overexpression in blood-brain barrier and blood-cerebrospinal fluid barrier is well recognized as the drug resistance mechanism of refractory epilepsy. Here, we established the drug-resistant epilepsy Sprague-Dawley rat model induced by Coriaria Lactone and treated these rats with topiramate and verapamil and low dose, middle dose, and high dose of spasmolytic powder by intragastric administration for 1 week. Electroencephalogram, real-time PCR, and immunohistochemistry were respectively used to detect epileptic discharge frequencies and amplitudes and expression of mdrl mRNA and Pgp on hippocampus and temporal lobe of rats. The results showed that the seizure decreases significantly in the high- and middle-dose groups of spasmolytic powder and topiramate group; in addition, mdr1 mRNA and Pgp expressions on hippocampus and temporal lobe of these drug intervention groups were significantly less than the model group (P < 0.05). These findings indicate that inhibition of intracephalic Pgp expression is possibly one of mechanisms of spasmolytic powder treating refractory epilepsy. PMID:23263794

  4. [Epileptic manifestations following head injury (author's transl)].

    PubMed

    Wessely, P

    1977-01-01

    An analysis is presented of the findings in a group of 300 patients with head injury, aged 15 years or over at the time of the accident, who subsequently developed epileptic manifestations. Early fits (including one case of immediate onset) were found in 33% of the cases (99 patients). In contrast to post-traumatic late epilepsy (PTE), which is a manifestation of a static process, early fits are triggered off by a dynamic process (brain oedema, haemorrhage) and are a sign of cerebral irritation, but do not represent a true form of epilepsy. Early fits are related to the acute traumatic state; the time limit is flexible, but lies in the region of 4 weeks following injury. Conversion of early fits to PTE (with or without a latent interval) occurred in 72% of the cases. This percentage is higher than the average incidence quoted in the literature and presumably arises partly from the selection criteria applied in this study. The time of appearance of early fits following injury is one factor which determines the prognosis. Fits appearing on the first day carry a relatively favourable prognosis and do not proceed to PTE in 41% of the cases, whereas this percentage shrinks to 15% in the case of fits appearing from the second week onwards. Early fits are an isolated occurrence in one third of the cases; progression to PTE is less frequent in these patients than following frequent, repeated convulsions. Furthermore, the incidence of early fits is dependent, to a large extent, on traumatological and clinical factors: the combination of unconsciousness of over three hours' duration, neurological signs referable to the central nervous system, persistent organic psychotic syndrome and intracranial bleeding leads to a significantly higher incidence of early fits than unconsciousness of less than three hours' duration and absence of neurological signs in patients who, moreover, do not display features of the psychotic syndrome, and shows a greater tendency to early fits even

  5. Interictal spikes and epileptic seizures: their relationship and underlying rhythmicity.

    PubMed

    Karoly, Philippa J; Freestone, Dean R; Boston, Ray; Grayden, David B; Himes, David; Leyde, Kent; Seneviratne, Udaya; Berkovic, Samuel; O'Brien, Terence; Cook, Mark J

    2016-04-01

    We report on a quantitative analysis of electrocorticography data from a study that acquired continuous ambulatory recordings in humans over extended periods of time. The objectives were to examine patterns of seizures and spontaneous interictal spikes, their relationship to each other, and the nature of periodic variation. The recorded data were originally acquired for the purpose of seizure prediction, and were subsequently analysed in further detail. A detection algorithm identified potential seizure activity and a template matched filter was used to locate spikes. Seizure events were confirmed manually and classified as either clinically correlated, electroencephalographically identical but not clinically correlated, or subclinical. We found that spike rate was significantly altered prior to seizure in 9 out of 15 subjects. Increased pre-ictal spike rate was linked to improved predictability; however, spike rate was also shown to decrease before seizure (in 6 out of the 9 subjects). The probability distribution of spikes and seizures were notably similar, i.e. at times of high seizure likelihood the probability of epileptic spiking also increased. Both spikes and seizures showed clear evidence of circadian regulation and, for some subjects, there were also longer term patterns visible over weeks to months. Patterns of spike and seizure occurrence were highly subject-specific. The pre-ictal decrease in spike rate is not consistent with spikes promoting seizures. However, the fact that spikes and seizures demonstrate similar probability distributions suggests they are not wholly independent processes. It is possible spikes actively inhibit seizures, or that a decreased spike rate is a secondary symptom of the brain approaching seizure. If spike rate is modulated by common regulatory factors as seizures then spikes may be useful biomarkers of cortical excitability.media-1vid110.1093/brain/aww019_video_abstractaww019_video_abstract. PMID:26912639

  6. Rs6295 promoter variants of the serotonin type 1A receptor are differentially activated by c-Jun in vitro and correlate to transcript levels in human epileptic brain tissue.

    PubMed

    Pernhorst, Katharina; van Loo, Karen M J; von Lehe, Marec; Priebe, Lutz; Cichon, Sven; Herms, Stefan; Hoffmann, Per; Helmstaedter, Christoph; Sander, Thomas; Schoch, Susanne; Becker, Albert J

    2013-03-01

    Many brain disorders, including epilepsy, migraine and depression, manifest with episodic symptoms that may last for various time intervals. Transient alterations of neuronal function such as related to serotonin homeostasis generally underlie this phenomenon. Several nucleotide polymorphisms (SNPs) in gene promoters associated with these diseases have been described. For obvious reasons, their regulatory roles on gene expression particularly in human brain tissue remain largely enigmatic. The rs6295 G-/C-allelic variant is located in the promoter region of the human HTR1a gene, encoding the G-protein-coupled receptor for 5-hydroxytryptamine (5HT1AR). In addition to reported transcriptional repressor binding, our bioinformatic analyses predicted a reduced binding affinity of the transcription factor (TF) c-Jun for the G-allele. In vitro luciferase transfection assays revealed c-Jun to (a) activate the rs6295 C- significantly stronger than the G-allelic variant and (b) antagonize efficiently the repressive effect of Hes5 on the promoter. The G-allele of rs6295 is known to be associated with aspects of major depression and migraine. In order to address a potential role of rs6295 variants in human brain tissue, we have isolated DNA and mRNA from fresh frozen hippocampal tissue of pharmacoresistant temporal lobe epilepsy (TLE) patients (n=140) after epilepsy surgery for seizure control. We carried out SNP genotyping studies and mRNA analyses in order to determine HTR1a mRNA expression in human hippocampal samples stratified according to the rs6295 allelic variant. The mRNA expression of HTR1a was significantly more abundant in hippocampal mRNA of TLE patients homozygous for the rs6295 C-allele as compared to those with the GG-genotype. These data may point to a novel, i.e., rs6295 allelic variant and c-Jun dependent transcriptional 5HT1AR 'receptoropathy'. PMID:23333373

  7. Epileptic Hypergraphia: The Impact of Prolific Writing on Language Creativity

    ERIC Educational Resources Information Center

    Ammari, Elham H.

    2012-01-01

    Catalyzed academic concerns have been shown so far to tackle the issue of temporal lobe epileptic hypergraphia and the extent of its creativity. Temporal lobe epilepsy hence, (TLE) as a neurological brain disorder, has captured the attention of concerned scholars ever since. A constellation of TLE and its cohorts have baffled scientists,…

  8. GRIN1 Mutations in Early-Onset Epileptic Encephalopathy.

    PubMed

    Chen, Wenjuan; Yuan, Hongjie

    2015-06-01

    Investigators from Yokohama City University and other medical centers in Israel and Japan reported mutations on N-methyl-D-aspartate (NMDA) receptors subunit GRIN1 (GluN1) identified in patients with nonsyndromic intellectual disability and early-onset epileptic encephalopathy. PMID:26933583

  9. Public Provision for Epileptics in the United States.

    ERIC Educational Resources Information Center

    Best, Harry

    A sociological study, the text reports data concerning epilepsy and public provisions for the epileptic. The general state of persons with epilepsy is discussed in terms of definition, general conditions, etiology, recovery or improvement, numbers in the United States, trends in numbers, sex distribution, age distribution, age at onset, race and…

  10. Organization and chemical neuroanatomy of the African elephant (Loxodonta africana) hippocampus.

    PubMed

    Patzke, Nina; Olaleye, Olatunbosun; Haagensen, Mark; Hof, Patrick R; Ihunwo, Amadi O; Manger, Paul R

    2014-09-01

    Elephants are thought to possess excellent long-term spatial-temporal and social memory, both memory types being at least in part hippocampus dependent. Although the hippocampus has been extensively studied in common laboratory mammalian species and humans, much less is known about comparative hippocampal neuroanatomy, and specifically that of the elephant. Moreover, the data available regarding hippocampal size of the elephant are inconsistent. The aim of the current study was to re-examine hippocampal size and provide a detailed neuroanatomical description of the hippocampus in the African elephant. In order to examine the hippocampal size the perfusion-fixed brains of three wild-caught adult male African elephants, aged 20-30 years, underwent MRI scanning. For the neuroanatomical description brain sections containing the hippocampus were stained for Nissl, myelin, calbindin, calretinin, parvalbumin and doublecortin. This study demonstrates that the elephant hippocampus is not unduly enlarged, nor specifically unusual in its internal morphology. The elephant hippocampus has a volume of 10.84 ± 0.33 cm³ and is slightly larger than the human hippocampus (10.23 cm(3)). Histological analysis revealed the typical trilaminated architecture of the dentate gyrus (DG) and the cornu ammonis (CA), although the molecular layer of the dentate gyrus appears to have supernumerary sublaminae compared to other mammals. The three main architectonic fields of the cornu ammonis (CA1, CA2, and CA3) could be clearly distinguished. Doublecortin immunostaining revealed the presence of adult neurogenesis in the elephant hippocampus. Thus, the elephant exhibits, for the most part, what might be considered a typically mammalian hippocampus in terms of both size and architecture. PMID:23728481

  11. The hippocampus and memory for orderly stimulus relations.

    PubMed

    Dusek, J A; Eichenbaum, H

    1997-06-24

    Human declarative memory involves a systematic organization of information that supports generalizations and inferences from acquired knowledge. This kind of memory depends on the hippocampal region in humans, but the extent to which animals also have declarative memory, and whether inferential expression of memory depends on the hippocampus in animals, remains a major challenge in cognitive neuroscience. To examine these issues, we used a test of transitive inference pioneered by Piaget to assess capacities for systematic organization of knowledge and logical inference in children. In our adaptation of the test, rats were trained on a set of four overlapping odor discrimination problems that could be encoded either separately or as a single representation of orderly relations among the odor stimuli. Normal rats learned the problems and demonstrated the relational memory organization through appropriate transitive inferences about items not presented together during training. By contrast, after disconnection of the hippocampus from either its cortical or subcortical pathway, rats succeeded in acquiring the separate discrimination problems but did not demonstrate transitive inference, indicating that they had failed to develop or could not inferentially express the orderly organization of the stimulus elements. These findings strongly support the view that the hippocampus mediates a general declarative memory capacity in animals, as it does in humans. PMID:9192700

  12. Dystrophin Distribution and Expression in Human and Experimental Temporal Lobe Epilepsy

    PubMed Central

    Hendriksen, Ruben G. F.; Schipper, Sandra; Hoogland, Govert; Schijns, Olaf E. M. G.; Dings, Jim T. A.; Aalbers, Marlien W.; Vles, Johan S. H.

    2016-01-01

    Objective: Dystrophin is part of a protein complex that connects the cytoskeleton to the extracellular matrix. In addition to its role in muscle tissue, it functions as an anchoring protein within the central nervous system such as in hippocampus and cerebellum. Its presence in the latter regions is illustrated by the cognitive problems seen in Duchenne Muscular Dystrophy (DMD). Since epilepsy is also supposed to constitute a comorbidity of DMD, it is hypothesized that dystrophin plays a role in neuronal excitability. Here, we aimed to study brain dystrophin distribution and expression in both, human and experimental temporal lobe epilepsy (TLE). Method: Regional and cellular dystrophin distribution was evaluated in both human and rat hippocampi and in rat cerebellar tissue by immunofluorescent colocalization with neuronal (NeuN and calbindin) and glial (GFAP) markers. In addition, hippocampal dystrophin levels were estimated by Western blot analysis in biopsies from TLE patients, post-mortem controls, amygdala kindled (AK)-, and control rats. Results: Dystrophin was expressed in all hippocampal pyramidal subfields and in the molecular-, Purkinje-, and granular cell layer of the cerebellum. In these regions it colocalized with GFAP, suggesting expression in astrocytes such as Bergmann glia (BG) and velate protoplasmic astrocytes. In rat hippocampus and cerebellum there were neither differences in dystrophin positive cell types, nor in the regional dystrophin distribution between AK and control animals. Quantitatively, hippocampal full-length dystrophin (Dp427) levels were about 60% higher in human TLE patients than in post-mortem controls (p < 0.05), whereas the level of the shorter Dp71 isoform did not differ. In contrast, AK animals showed similar dystrophin levels as controls. Conclusion: Dystrophin is ubiquitously expressed by astrocytes in the human and rat hippocampus and in the rat cerebellum. Hippocampal full-length dystrophin (Dp427) levels are upregulated

  13. Dynamic analysis of heartbeat rate signals of epileptics using multidimensional phase space reconstruction approach

    NASA Astrophysics Data System (ADS)

    Su, Zhi-Yuan; Wu, Tzuyin; Yang, Po-Hua; Wang, Yeng-Tseng

    2008-04-01

    The heartbeat rate signal provides an invaluable means of assessing the sympathetic-parasympathetic balance of the human autonomic nervous system and thus represents an ideal diagnostic mechanism for detecting a variety of disorders such as epilepsy, cardiac disease and so forth. The current study analyses the dynamics of the heartbeat rate signal of known epilepsy sufferers in order to obtain a detailed understanding of the heart rate pattern during a seizure event. In the proposed approach, the ECG signals are converted into heartbeat rate signals and the embedology theorem is then used to construct the corresponding multidimensional phase space. The dynamics of the heartbeat rate signal are then analyzed before, during and after an epileptic seizure by examining the maximum Lyapunov exponent and the correlation dimension of the attractors in the reconstructed phase space. In general, the results reveal that the heartbeat rate signal transits from an aperiodic, highly-complex behaviour before an epileptic seizure to a low dimensional chaotic motion during the seizure event. Following the seizure, the signal trajectories return to a highly-complex state, and the complex signal patterns associated with normal physiological conditions reappear.

  14. The dynamics of the epileptic brain reveal long-memory processes.

    PubMed

    Cook, Mark J; Varsavsky, Andrea; Himes, David; Leyde, Kent; Berkovic, Samuel Frank; O'Brien, Terence; Mareels, Iven

    2014-01-01

    The pattern of epileptic seizures is often considered unpredictable and the interval between events without correlation. A number of studies have examined the possibility that seizure activity respects a power-law relationship, both in terms of event magnitude and inter-event intervals. Such relationships are found in a variety of natural and man-made systems, such as earthquakes or Internet traffic, and describe the relationship between the magnitude of an event and the number of events. We postulated that human inter-seizure intervals would follow a power-law relationship, and furthermore that evidence for the existence of a long-memory process could be established in this relationship. We performed a post hoc analysis, studying eight patients who had long-term (up to 2 years) ambulatory intracranial EEG data recorded as part of the assessment of a novel seizure prediction device. We demonstrated that a power-law relationship could be established in these patients (β = - 1.5). In five out of the six subjects whose data were sufficiently stationary for analysis, we found evidence of long memory between epileptic events. This memory spans time scales from 30 min to 40 days. The estimated Hurst exponents range from 0.51 to 0.77 ± 0.01. This finding may provide evidence of phase-transitions underlying the dynamics of epilepsy. PMID:25386160

  15. Subunit Composition of Neurotransmitter Receptors in the Immature and in the Epileptic Brain

    PubMed Central

    Sánchez Fernández, Iván; Loddenkemper, Tobias

    2014-01-01

    Neuronal activity is critical for synaptogenesis and the development of neuronal networks. In the immature brain excitation predominates over inhibition facilitating the development of normal brain circuits, but also rendering it more susceptible to seizures. In this paper, we review the evolution of the subunit composition of neurotransmitter receptors during development, how it promotes excitation in the immature brain, and how this subunit composition of neurotransmission receptors may be also present in the epileptic brain. During normal brain development, excitatory glutamate receptors peak in function and gamma-aminobutiric acid (GABA) receptors are mainly excitatory rather than inhibitory. A growing body of evidence from animal models of epilepsy and status epilepticus has demonstrated that the brain exposed to repeated seizures presents a subunit composition of neurotransmitter receptors that mirrors that of the immature brain and promotes further seizures and epileptogenesis. Studies performed in samples from the epileptic human brain have also found a subunit composition pattern of neurotransmitter receptors similar to the one found in the immature brain. These findings provide a solid rationale for tailoring antiepileptic treatments to the specific subunit composition of neurotransmitter receptors and they provide potential targets for the development of antiepileptogenic treatments. PMID:25295256

  16. Hippocampus minor, calcar avis, and the Huxley-Owen debate.

    PubMed

    Owen, Christopher M; Howard, Allyson; Binder, Devin K

    2009-12-01

    On the bicentennial of Darwin's birth, we describe the origin of the calcar avis and summarize the debate around this structure, which played a central role in the evolution debate in the mid-19th century. We performed a comprehensive review of relevant neuroanatomic literature, bibliographic sources, and 19th century primary sources. Once known as the hippocampus minor, the structure now known as the calcar avis is an involution of the ventricular wall produced by the calcarine fissure. A heated debate raged between 2 prominent scientific theorists, Sir Richard Owen and Thomas Henry Huxley, over the presence of the hippocampus minor in apes versus humans. Owen put forward the lack of an identifiable hippocampus minor in humans as part of an attempt to debunk evolution. A bitter personal and academic rivalry ensued, as Huxley conducted his own dissections to refute Owen's claims. Huxley ultimately dismantled Owen's premises, securing the epithet "Darwin's bulldog" for his defense of the theory of evolution. Thus, this relatively obscure neuroanatomic landmark served as a pivotal point of contention in the most popularized and acrimonious evolutionary debate of the 19th century. PMID:19934969

  17. Beta-endorphin, somatostatin, and prolactin levels in cerebrospinal fluid of epileptic patients after generalised convulsion.

    PubMed Central

    Pitkänen, A; Jolkkonen, J; Riekkinen, P

    1987-01-01

    The possible role of different peptidergic systems in the postictal stage of human epilepsy was studied by measuring beta-endorphin, somatostatin, and prolactin levels by radioimmunoassay of cerebrospinal fluid (CSF) from nine epileptic patients. The first sample was taken within 2 hours after generalised tonic-clonic convulsion, and the second sample was obtained interictally after 1-4 days without any kind of clinically observable seizures. beta-endorphin was elevated postictally (p = 0.044) compared with interictal levels. SLI and PROL were similar in both samples. The present study suggests that in humans beta-endorphin is released into CSF during generalised seizures. This may indicate that neurons containing beta-endorphin are activated during a seizure. PMID:2890716

  18. Basal dendritic length is reduced in the rat hippocampus following bilateral vestibular deafferentation.

    PubMed

    Balabhadrapatruni, Sangeeta; Zheng, Yiwen; Napper, Ruth; Smith, Paul F

    2016-05-01

    Some previous studies in humans have shown that bilateral loss of vestibular function is associated with a significant bilateral atrophy of the hippocampus, which correlated with the patients' spatial memory deficits. By contrast, studies in rats have failed to detect any changes in hippocampal volume following bilateral vestibular loss. Therefore, in this study we investigated whether bilateral vestibular deafferentation (BVD) might result in more subtle morphological changes in the rat hippocampus, involving alterations in dendritic intersections, using Golgi staining and Sholl analysis. We found that at 1month following BVD, there was a significant decrease in basal (P⩽0.0001) but not apical dendritic intersections in the CA1 region of the hippocampus compared to sham-operated animals and anaesthetic controls. However, dendritic branching was not significantly affected. These results suggest that the rat hippocampus does undergo subtle morphological changes following bilateral vestibular loss, and that they may be in the form of alterations in dendritic structure. PMID:26976094

  19. Pursuit-paretic and epileptic nystagmus in MELAS.

    PubMed

    Choi, Seo Young; Kim, Yeonjung; Oh, Sea Won; Jeong, Seong-Hae; Kim, Ji Soo

    2012-06-01

    A 27-year-old man with MELAS 3243 mutation developed a right homonymous hemianopia, left beating nystagmus, and impaired smooth pursuit (SP) to the left. Intermittently, the left beating nystagmus changed to right beating with rightward eye and head deviation and associated altered mental status. Each episode lasted several minutes. MRI revealed restricted diffusion in left parieto-temporo-occipital cortices. During the ictus, electroencephalogram showed epileptic discharges in the left temporo-occipital region, and single photon emission computed tomography demonstrated hyperperfusion in the same area. The interictal left beating nystagmus may be ascribed to contralesional bias of SP imbalance since the parieto-temporo-occipital region is involved in the generation of SP. The ictal right beating nystagmus and rightward head and eye deviation indicate coactivation of the SP areas and parietal eye field. This report documents the novel co-occurrence of pursuit-paretic and epileptic nystagmus. PMID:22418087

  20. Drowning risks to epileptic children: a study from Hawaii.

    PubMed Central

    Pearn, J; Bart, R; Yamaoka, R

    1978-01-01

    The role of epileptiform seizures in causing drowning and near-drowning among children was studied by examining the case reports of all 140 childhood immersion accidents that occurred in an area of Hawaii over five years. Four of the 140 immersion accidents were caused partly by epileptiform seizures, but none were fatal. The combined results of the Hawaiian and Brisbane studies (total population studied over five years 1 600 000) showed that no epileptic children died from accidents in the sea or in swimming pools; and the 2.9% incidence of immersion accidents due to seizures in the Hawaiian study compares well with the incidence found in other series. If an epileptic child is mentally normal, well controlled with anticonvulsants, and supervised in the water then the risk of drowning is very small. PMID:709318

  1. Assortative mixing in functional brain networks during epileptic seizures

    NASA Astrophysics Data System (ADS)

    Bialonski, Stephan; Lehnertz, Klaus

    2013-09-01

    We investigate assortativity of functional brain networks before, during, and after one-hundred epileptic seizures with different anatomical onset locations. We construct binary functional networks from multi-channel electroencephalographic data recorded from 60 epilepsy patients; and from time-resolved estimates of the assortativity coefficient, we conclude that positive degree-degree correlations are inherent to seizure dynamics. While seizures evolve, an increasing assortativity indicates a segregation of the underlying functional network into groups of brain regions that are only sparsely interconnected, if at all. Interestingly, assortativity decreases already prior to seizure end. Together with previous observations of characteristic temporal evolutions of global statistical properties and synchronizability of epileptic brain networks, our findings may help to gain deeper insights into the complicated dynamics underlying generation, propagation, and termination of seizures.

  2. Development of a neurostimulator for studies of epileptic crisis

    NASA Astrophysics Data System (ADS)

    Niro, J.; Manso, J.; Ballina, F.; Periolo, S.; D'Atellis, C.; Ponce, S.; Barroso, M.; Anessi, C.; Kochen, S.

    2007-11-01

    This work describes the development and use of a multi-channel, programmable physiological stimulator. The device is intended for the detection of epileptic events and crisis prediction using encephalograms. The animals were followed by the kindling model. The system program accepts several inputs of stimulation parameters such as, pulse width, separation between pulses, pulse intensity and total number of pulses. The stimulator generates constant-current, bipolar pulses with a maximum amplitude of 5 mA and a resolution of 50μA. As regards voltage, the maximum amplitude is 150 V. The stimulator was constructed with a microcontroller (PIC18F4550), the latter version being controlled by a personal computer. Experiments of achieving the epileptic events were carried out on rats.

  3. Hippocampus shape analysis for temporal lobe epilepsy detection in magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Kohan, Zohreh; Azmi, Reza

    2016-03-01

    There are evidences in the literature that Temporal Lobe Epilepsy (TLE) causes some lateralized atrophy and deformation on hippocampus and other substructures of the brain. Magnetic Resonance Imaging (MRI), due to high-contrast soft tissue imaging, is one of the most popular imaging modalities being used in TLE diagnosis and treatment procedures. Using an algorithm to help clinicians for better and more effective shape deformations analysis could improve the diagnosis and treatment of the disease. In this project our purpose is to design, implement and test a classification algorithm for MRIs based on hippocampal asymmetry detection using shape and size-based features. Our method consisted of two main parts; (1) shape feature extraction, and (2) image classification. We tested 11 different shape and size features and selected four of them that detect the asymmetry in hippocampus significantly in a randomly selected subset of the dataset. Then, we employed a support vector machine (SVM) classifier to classify the remaining images of the dataset to normal and epileptic images using our selected features. The dataset contains 25 patient images in which 12 cases were used as a training set and the rest 13 cases for testing the performance of classifier. We measured accuracy, specificity and sensitivity of, respectively, 76%, 100%, and 70% for our algorithm. The preliminary results show that using shape and size features for detecting hippocampal asymmetry could be helpful in TLE diagnosis in MRI.

  4. Houttuyniae Herba Attenuates Kainic Acid-Induced Neurotoxicity via Calcium Response Modulation in the Mouse Hippocampus.

    PubMed

    Kim, Hyo Geun; Jeong, Hyun Uk; Hong, Sung In; Oh, Myung Sook

    2015-12-01

    Epilepsy is a complex neurological disorder characterized by the repeated occurrence of electrical activity known as seizures. This activity induces increased intracellular calcium, which ultimately leads to neuronal damage. Houttuyniae Herba, the aerial part of Houttuynia cordata, has various pharmacological effects and is widely used as a traditional herb. In the present study, we evaluated the protective effects of Houttuyniae Herba water extract on kainic acid-induced neurotoxicity. Kainic acid directly acts on calcium release, resulting in seizure behavior, neuronal damage, and cognitive impairment. In a rat primary hippocampal culture system, Houttuyniae Herba water extract significantly protected neuronal cells from kainic acid toxicity. In a seizure model where mice received intracerebellar kainic acid injections, Houttuyniae Herba water extract treatment resulted in a lower seizure stage score, ameliorated cognitive impairment, protected neuronal cells against kainic acid-induced toxicity, and suppressed neuronal degeneration in the hippocampus. In addition, Houttuyniae Herba water extract regulated increases in the intracellular calcium level, its related downstream pathways (reactive oxygen species production and mitochondrial dysfunction), and calcium/calmodulin complex kinase type II immunoreactivity in the mouse hippocampus, which resulted from calcium influx stimulation induced by kainic acid. These results demonstrate the neuroprotective effects of Houttuyniae Herba water extract through inhibition of calcium generation in a kainic acid-induced epileptic model. PMID:26366753

  5. Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus: possible implications for epilepsy.

    PubMed

    Ievglevskyi, O; Isaev, D; Netsyk, O; Romanov, A; Fedoriuk, M; Maximyuk, O; Isaeva, E; Akaike, N; Krishtal, O

    2016-08-01

    Acid-sensing ion channels (ASICs) play an important role in numerous functions in the central and peripheral nervous systems ranging from memory and emotions to pain. The data correspond to a recent notion that each neuron and many glial cells of the mammalian brain express at least one member of the ASIC family. However, the mechanisms underlying the involvement of ASICs in neuronal activity are poorly understood. However, there are two exceptions, namely, the straightforward role of ASICs in proton-based synaptic transmission in certain brain areas and the role of the Ca(2+)-permeable ASIC1a subtype in ischaemic cell death. Using a novel orthosteric ASIC antagonist, we have found that ASICs specifically control the frequency of spontaneous inhibitory synaptic activity in the hippocampus. Inhibition of ASICs leads to a strong increase in the frequency of spontaneous inhibitory postsynaptic currents. This effect is presynaptic because it is fully reproducible in single synaptic boutons attached to isolated hippocampal neurons. In concert with this observation, inhibition of the ASIC current diminishes epileptic discharges in a low Mg(2+) model of epilepsy in hippocampal slices and significantly reduces kainate-induced discharges in the hippocampus in vivo Our results reveal a significant novel role for ASICs.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377725

  6. Quadriplegia Following Epileptic Seizure : Things to Keep in Mind

    PubMed Central

    Yeşilbudak, Zülal; Şişman, Lokman; Uca, Ali Ulvi

    2016-01-01

    People with epilepsy are believed to be at a higher risk of incurring accidental injury than people who do not have seizures. The incidence of injury, either due to seizure or accident as a consequent of seizure is also high and varies from 0.03% to 3%. The most common injuries are head contusions, lacerations, burns and fractures. In this article, we present a case of quadriplegia after a generalized epileptic seizure. PMID:27226869

  7. Quadriplegia Following Epileptic Seizure : Things to Keep in Mind.

    PubMed

    Kozak, Hasan Hüseyin; Yeşilbudak, Zülal; Şişman, Lokman; Uca, Ali Ulvi

    2016-05-01

    People with epilepsy are believed to be at a higher risk of incurring accidental injury than people who do not have seizures. The incidence of injury, either due to seizure or accident as a consequent of seizure is also high and varies from 0.03% to 3%. The most common injuries are head contusions, lacerations, burns and fractures. In this article, we present a case of quadriplegia after a generalized epileptic seizure. PMID:27226869

  8. Epileptic seizure prediction by non-linear methods

    SciTech Connect

    Hively, L.M.; Clapp, N.E.; Day, C.S.; Lawkins, W.F.

    1999-01-12

    This research discloses methods and apparatus for automatically predicting epileptic seizures monitor and analyze brain wave (EEG or MEG) signals. Steps include: acquiring the brain wave data from the patient; digitizing the data; obtaining nonlinear measures of the data via chaotic time series analysis tools; obtaining time serial trends in the nonlinear measures; comparison of the trend to known seizure predictors; and providing notification that a seizure is forthcoming. 76 figs.

  9. Estimation of degree of synchronization in epileptic brain

    NASA Astrophysics Data System (ADS)

    Moskalenko, Olga I.; Koronovskii, Alexey A.; Pavlov, Alexey N.; Hramov, Alexander E.; Zhuravlev, Maksim O.

    2016-03-01

    The method for calculation of zero conditional Lyapunov exponent from time series has been proposed. Such method is shown to define the degree of synchronization of the regime realized in the system. It has been applied to real experimental neurophysiological time series represented by electroencephalograms of WAG/Rij rats having genetic predisposition to absence-epilepsy. The degree of synchronization in epileptic brain has been found.

  10. Epileptic seizure prediction by non-linear methods

    DOEpatents

    Hively, Lee M.; Clapp, Ned E.; Daw, C. Stuart; Lawkins, William F.

    1999-01-01

    Methods and apparatus for automatically predicting epileptic seizures monitor and analyze brain wave (EEG or MEG) signals. Steps include: acquiring the brain wave data from the patient; digitizing the data; obtaining nonlinear measures of the data via chaotic time series analysis tools; obtaining time serial trends in the nonlinear measures; comparison of the trend to known seizure predictors; and providing notification that a seizure is forthcoming.

  11. Hippocampus in health and disease: An overview

    PubMed Central

    Anand, Kuljeet Singh; Dhikav, Vikas

    2012-01-01

    Hippocampus is a complex brain structure embedded deep into temporal lobe. It has a major role in learning and memory. It is a plastic and vulnerable structure that gets damaged by a variety of stimuli. Studies have shown that it also gets affected in a variety of neurological and psychiatric disorders. In last decade or so, lot has been learnt about conditions that affect hippocampus and produce changes ranging from molecules to morphology. Progresses in radiological delineation, electrophysiology, and histochemical characterization have made it possible to study this archicerebral structure in greater detail. Present paper attempts to give an overview of hippocampus, both in health and diseases. PMID:23349586

  12. The stressed hippocampus, synaptic plasticity and lost memories.

    PubMed

    Kim, Jeansok J; Diamond, David M

    2002-06-01

    Stress is a biologically significant factor that, by altering brain cell properties, can disturb cognitive processes such as learning and memory, and consequently limit the quality of human life. Extensive rodent and human research has shown that the hippocampus is not only crucially involved in memory formation, but is also highly sensitive to stress. So, the study of stress-induced cognitive and neurobiological sequelae in animal models might provide valuable insight into the mnemonic mechanisms that are vulnerable to stress. Here, we provide an overview of the neurobiology of stress memory interactions, and present a neural endocrine model to explain how stress modifies hippocampal functioning. PMID:12042880

  13. Hidden Markov chain modeling for epileptic networks identification.

    PubMed

    Le Cam, Steven; Louis-Dorr, Valérie; Maillard, Louis

    2013-01-01

    The partial epileptic seizures are often considered to be caused by a wrong balance between inhibitory and excitatory interneuron connections within a focal brain area. These abnormal balances are likely to result in loss of functional connectivities between remote brain structures, while functional connectivities within the incriminated zone are enhanced. The identification of the epileptic networks underlying these hypersynchronies are expected to contribute to a better understanding of the brain mechanisms responsible for the development of the seizures. In this objective, threshold strategies are commonly applied, based on synchrony measurements computed from recordings of the electrophysiologic brain activity. However, such methods are reported to be prone to errors and false alarms. In this paper, we propose a hidden Markov chain modeling of the synchrony states with the aim to develop a reliable machine learning methods for epileptic network inference. The method is applied on a real Stereo-EEG recording, demonstrating consistent results with the clinical evaluations and with the current knowledge on temporal lobe epilepsy. PMID:24110697

  14. [Portable Epileptic Seizure Monitoring Intelligent System Based on Android System].

    PubMed

    Liang, Zhenhu; Wu, Shufeng; Yang, Chunlin; Jiang, Zhenzhou; Yu, Tao; Lu, Chengbiao; Li, Xiaoli

    2016-02-01

    The clinical electroencephalogram (EEG) monitoring systems based on personal computer system can not meet the requirements of portability and home usage. The epilepsy patients have to be monitored in hospital for an extended period of time, which imposes a heavy burden on hospitals. In the present study, we designed a portable 16-lead networked monitoring system based on the Android smart phone. The system uses some technologies including the active electrode, the WiFi wireless transmission, the multi-scale permutation entropy (MPE) algorithm, the back-propagation (BP) neural network algorithm, etc. Moreover, the software of Android mobile application can realize the processing and analysis of EEG data, the display of EEG waveform and the alarm of epileptic seizure. The system has been tested on the mobile phones with Android 2. 3 operating system or higher version and the results showed that this software ran accurately and steadily in the detection of epileptic seizure. In conclusion, this paper provides a portable and reliable solution for epileptic seizure monitoring in clinical and home applications. PMID:27382736

  15. Efficacy of Attribution Retraining on Mental Health of Epileptic Children

    PubMed Central

    Pourmohamadreza Tajrishi, Masoume; Abbasi, Saeid; Najafi Fard, Tahereh; Yousefi, Saheb; Mohammadi Malek Abadi, Athar; Delavar Kasmaei, Hosein

    2015-01-01

    Background: Epilepsy affects children’s quality of life and leads to social and mental problems. Promoting the mental health of children, especially epileptic ones, and preventing problems affecting them constitute major concerns for every country. Mental health promotion requires intervention programs. Objectives: We sought to assess the efficacy of attribution retraining on the mental health of epileptic children. Patients and Methods: The present study is a semi-experimental investigation with a pretest and posttest design and includes a control group. Thirty children, comprising 17 boys and 13 girls, were selected randomly from the Iranian epilepsy association in Tehran and assigned to experimental and control groups. They answered to the general health questionnaire (Goldberg and Hiller, 1979). The experimental group participated in 11 training sessions (twice a week; 45 minutes for each session) and received attribution retraining. The data were analyzed using the multiple analysis of covariance. Results: The findings showed that the experimental group, in comparison with the control group, experienced a reduction in physical symptoms, anxiety and insomnia, social dysfunction, and depression and an increase in mental health significantly (P < 0.01) after the training sessions. There were no significant differences, however, between the two groups at 6 weeks’ follow-up. Conclusions: Attribution retraining improved mental health in the epileptic children in our study. It, therefore, seems to be an appropriate intervention for promoting the mental health of children. PMID:26568854

  16. Nonlinear analysis of epileptic activity in rabbit neocortex.

    PubMed

    Sarnthein, J; Abarbanel, H D; Pockberger, H

    1998-01-01

    We report on the nonlinear analysis of electroencephalogram (EEG) recordings in the rabbit visual cortex. Epileptic seizures were induced by local penicillin application and triggered by visual stimulation. The analysis procedures for nonlinear signals have been developed over the past few years and applied primarily to physical systems. This is an early application to biological systems and the first to EEG data. We find that during epileptic activity, both global and local embedding dimensions are reduced with respect to nonepileptic activity. Interestingly, these values are very low (dE approximately equal to 3) and do not change between preictal and tonic stages of epileptic activity, also the Lyapunov dimension remains constant. However, between these two stages the manifestations of the local dynamics change quite drastically, as can be seen, e.g., from the shape of the attractors. Furthermore, the largest Lyapunov exponent is reduced by a factor of about two in the second stage and characterizes the difference in dynamics. Thus, the occurrence of clinical symptoms associated with the tonic seizure activity seems to be mainly related to the local dynamics of the nonlinear system. These results thus seem to give a strong indication that the dynamics remains much the same in these stages of behavior, and changes are due to alterations in model parameters and consequent bifurcations of the observed orbits. PMID:9485585

  17. [Diagnosis and treatment of non-triggered single epileptic seizures].

    PubMed

    Martinez-Juarez, I E; Moreno, J; Ladino, L D; Castro, N; Hernandez-Vanegas, L; Burneo, J G; Hernandez-Ronquillo, L; Tellez-Zenteno, J F

    2016-08-16

    Epileptic seizures are one of the main reasons for neurological visits in an emergency department. Convulsions represent a traumatic event for the patient and the family, with significant medical and social consequences. Due to their prevalence and impact, the initial management is of vital importance. Although following the first epileptic seizure, early recurrence diminishes after establishing treatment with antiepileptic drugs, the forecast for developing epilepsy and long-term outcomes are not altered by any early intervention. Detailed questioning based on the symptoms of the convulsions, the patient's medical history and a full electroencephalogram and neuroimaging study make it possible to define the risk of recurrence of the seizure and the possible diagnosis of epilepsy. Epileptic abnormalities, the presence of old or new potentially epileptogenic brain lesions, as well as nocturnal seizures, increase the risk of recurrence. Physicians must assess each patient on an individual basis to determine the most suitable treatment, and explain the risk of not being treated versus the risk that exists if treatment with antiepileptic drugs is established. PMID:27439486

  18. Unstable periodic orbits in human epileptic hippocampal slices.

    PubMed

    Pen-Ning Yu; Min-Chi Hsiao; Dong Song; Liu, Charles Y; Heck, Christi N; Millett, David; Berger, Theodore W

    2014-01-01

    Inter-ictal activity is studied in hippocampal slices resected from patients with epilepsy using local field potential recording. Inter-ictal activity in the dentate gyrus (DG) is induced by high-potassium (8 mM), low-magnesium (0.25 mM) aCSF with additional 100 μM 4-aminopyridine(4-AP). The dynamics of the inter-ictal activity is investigated by developing the first return map with inter-pulse intervals. Unstable periodic orbits (UPOs) are detected in the hippocampal slice at the DG area according to both the topological recurrence method and the periodic orbit transform method. Surrogate analysis suggests the presence of UPOs in hippocampal slices from patients with epilepsy. This finding also suggests that inter-ictal activity is a chaotic system and will allow us to apply chaos control techniques to manipulate inter-ictal activity. PMID:25571314

  19. Impaired neurovascular coupling to ictal epileptic activity and spreading depolarization in a patient with subarachnoid hemorrhage: possible link to blood-brain barrier dysfunction.

    PubMed

    Winkler, Maren K L; Chassidim, Yoash; Lublinsky, Svetlana; Revankar, Gajanan S; Major, Sebastian; Kang, Eun-Jeung; Oliveira-Ferreira, Ana I; Woitzik, Johannes; Sandow, Nora; Scheel, Michael; Friedman, Alon; Dreier, Jens P

    2012-11-01

    Spreading depolarization describes a sustained neuronal and astroglial depolarization with abrupt ion translocation between intraneuronal and extracellular space leading to a cytotoxic edema and silencing of spontaneous activity. Spreading depolarizations occur abundantly in acutely injured human brain and are assumed to facilitate neuronal death through toxic effects, increased metabolic demand, and inverse neurovascular coupling. Inverse coupling describes severe hypoperfusion in response to spreading depolarization. Ictal epileptic events are less frequent than spreading depolarizations in acutely injured human brain but may also contribute to lesion progression through increased metabolic demand. Whether abnormal neurovascular coupling can occur with ictal epileptic events is unknown. Herein we describe a patient with aneurysmal subarachnoid hemorrhage in whom spreading depolarizations and ictal epileptic events were measured using subdural opto-electrodes for direct current electrocorticography and regional cerebral blood flow recordings with laser-Doppler flowmetry. Simultaneously, changes in tissue partial pressure of oxygen were recorded with an intraparenchymal oxygen sensor. Isolated spreading depolarizations and clusters of recurrent spreading depolarizations with persistent depression of spontaneous activity were recorded over several days followed by a status epilepticus. Both spreading depolarizations and ictal epileptic events where accompanied by hyperemic blood flow responses at one optode but mildly hypoemic blood flow responses at another. Of note, quantitative analysis of Gadolinium-diethylene-triamine-pentaacetic acid (DTPA)-enhanced magnetic resonance imaging detected impaired blood-brain barrier integrity in the region where the optode had recorded the mildly hypoemic flow responses. The data suggest that abnormal flow responses to spreading depolarizations and ictal epileptic events, respectively, may be associated with blood-brain barrier

  20. Dissection of Different Areas from Mouse Hippocampus

    PubMed Central

    Sultan, Faraz A.

    2016-01-01

    The hippocampus modulates a number of modules including memory consolidation, spatial navigation, temporal processing and emotion. A banana-shaped structure, the hippocampus is constituted of morphologically distinct subregions including the dentate gyrus, CA3 and CA1 (here, we do not distinguish the “hippocampus proper” which consists only of CA1, CA3 and smaller CA2 and CA4 areas, from the “hippocampal formation,” composed of these in addition to the dentate gyrus and subiculum). Distinct cell types give rise to unique axonal fiber pathways in the dentate gyrus, CA3 and CA1 subregions; accordingly, these areas may exhibit differential molecular profiles in response to a number of behavioral paradigms and pharmacological and genetic treatments. It is therefore in the interest of the investigator to dissect a specific subregion from the whole hippocampus. Here we outline a protocol for subregion-specific dissection from the adult mouse.

  1. Clustering Approach to Quantify Long-Term Spatio-Temporal Interactions in Epileptic Intracranial Electroencephalography

    PubMed Central

    Hegde, Anant; Erdogmus, Deniz; Shiau, Deng S.; Principe, Jose C.; Sackellares, Chris J.

    2007-01-01

    Abnormal dynamical coupling between brain structures is believed to be primarily responsible for the generation of epileptic seizures and their propagation. In this study, we attempt to identify the spatio-temporal interactions of an epileptic brain using a previously proposed nonlinear dependency measure. Using a clustering model, we determine the average spatial mappings in an epileptic brain at different stages of a complex partial seizure. Results involving 8 seizures from 2 epileptic patients suggest that there may be a fixed pattern associated with regional spatio-temporal dynamics during the interictal to pre-post-ictal transition. PMID:18317515

  2. Convulsive Syncope Induced by Ventricular Arrhythmia Masquerading as Epileptic Seizures: Case Report and Literature Review.

    PubMed

    Sabu, John; Regeti, Kalyani; Mallappallil, Mary; Kassotis, John; Islam, Hamidul; Zafar, Shoaib; Khan, Rafay; Ibrahim, Hiyam; Kanta, Romana; Sen, Shuvendu; Yousif, Abdalla; Nai, Qiang

    2016-08-01

    It is important but difficult to distinguish convulsive syncope from epileptic seizure in many patients. We report a case of a man who presented to emergency department after several witnessed seizure-like episodes. He had a previous medical history of systolic heart failure and automated implantable converter defibrillator (AICD) in situ. The differential diagnoses raised were epileptic seizures and convulsive syncope secondary to cardiac arrhythmia. Subsequent AICD interrogation revealed ventricular tachycardia and fibrillation (v-tach/fib). Since convulsive syncope and epileptic seizure share many similar clinical features, early diagnosis is critical for choosing the appropriate management and preventing sudden cardiac death in patients with presumed epileptic seizure. PMID:27429683

  3. Convulsive Syncope Induced by Ventricular Arrhythmia Masquerading as Epileptic Seizures: Case Report and Literature Review

    PubMed Central

    Sabu, John; Regeti, Kalyani; Mallappallil, Mary; Kassotis, John; Islam, Hamidul; Zafar, Shoaib; Khan, Rafay; Ibrahim, Hiyam; Kanta, Romana; Sen, Shuvendu; Yousif, Abdalla; Nai, Qiang

    2016-01-01

    It is important but difficult to distinguish convulsive syncope from epileptic seizure in many patients. We report a case of a man who presented to emergency department after several witnessed seizure-like episodes. He had a previous medical history of systolic heart failure and automated implantable converter defibrillator (AICD) in situ. The differential diagnoses raised were epileptic seizures and convulsive syncope secondary to cardiac arrhythmia. Subsequent AICD interrogation revealed ventricular tachycardia and fibrillation (v-tach/fib). Since convulsive syncope and epileptic seizure share many similar clinical features, early diagnosis is critical for choosing the appropriate management and preventing sudden cardiac death in patients with presumed epileptic seizure. PMID:27429683

  4. Uncaria rhynchophylla and rhynchophylline improved kainic acid-induced epileptic seizures via IL-1β and brain-derived neurotrophic factor.

    PubMed

    Ho, Tin-Yun; Tang, Nou-Ying; Hsiang, Chien-Yun; Hsieh, Ching-Liang

    2014-05-15

    Uncaria rhynchophylla (UR) has been used for the treatment of convulsions and epilepsy in traditional Chinese medicine. This study reported the major anti-convulsive signaling pathways and effective targets of UR and rhynchophylline (RP) using genomic and immunohistochemical studies. Epileptic seizure model was established by intraperitoneal injection of kainic acid (KA) in rats. Electroencephalogram and electromyogram recordings indicated that UR and RP improved KA-induced epileptic seizures. Toll-like receptor (TLR) and neurotrophin signaling pathways were regulated by UR in both cortex and hippocampus of KA-treated rats. KA upregulated the expression levels of interleukin-1β (IL-1β) and brain-derived neurotrophin factor (BDNF), which were involved in TLR and neurotrophin signaling pathways, respectively. However, UR and RP downregulated the KA-induced IL-1β and BDNF gene expressions. Our findings suggested that UR and RP exhibited anti-convulsive effects in KA-induced rats via the regulation of TLR and neurotrophin signaling pathways, and the subsequent inhibition of IL-1β and BDNF gene expressions. PMID:24636743

  5. Differences in mitochondrial function in homogenated samples from healthy and epileptic specific brain tissues revealed by high-resolution respirometry.

    PubMed

    Burtscher, Johannes; Zangrandi, Luca; Schwarzer, Christoph; Gnaiger, Erich

    2015-11-01

    Mitochondrial dysfunction and oxidative stress are strongly implicated in neurodegenerative diseases and epilepsy. Strikingly, neurodegenerative diseases show regional specificity in vulnerability and follow distinct patterns of neuronal loss. A challenge is to understand, why mitochondria fail in particular brain regions under specific pathological conditions. A potential explanation could be provided by regional or cellular specificity of mitochondrial function. We applied high-resolution respirometry to analyze the integrated Complex I- and II (CI and CII)-linked respiration, the activity of Complex IV, and the combined CI&II-linked oxidative phosphorylation (OXPHOS)- and electron-transfer system (ETS)-capacity in microsamples obtained from distinct regions of the mouse brain. We compared different approaches to assess mitochondrial density and suggest flux control ratios as a valid method to normalize respiration to mitochondrial density. This approach revealed significant differences of CI- and CII-linked OXPHOS capacity and coupling control between motor cortex, striatum, hippocampus and pons of naïve mice. CI-linked respiration was highest in motor cortex, while CII-linked respiration predominated in the striatum. To investigate if this method could also determine differences in normal and disease states within the same brain region, we compared hippocampal homogenates in a chronic epilepsy model. Three weeks after stereotaxic injection of kainate, there was a down-regulation of CI- and upregulation of CII-linked respiration in the resulting epileptic ipsilateral hippocampus compared to the contralateral one. In summary, respirometric OXPHOS analysis provides a very sensitive diagnostic approach using small amounts of distinct brain tissues. In a single assay, information is obtained on numerous OXPHOS parameters as indicators of tissue-specific mitochondrial performance. PMID:26516105

  6. Neocortical slices from adult chronic epileptic rats exhibit discharges of higher voltages and broader spread.

    PubMed

    Serafini, R; Dettloff, S; Loeb, J A

    2016-05-13

    Much of the current understanding of epilepsy mechanisms has been built on data recorded with one or a few electrodes from temporal lobe slices of normal young animals stimulated with convulsants. Mechanisms of adult, extratemporal, neocortical chronic epilepsy have not been characterized as much. A more advanced understanding of epilepsy mechanisms can be obtained by recording epileptiform discharges simultaneously from multiple points of an epileptic focus so as to define their sites of initiation and pathways of spreading. Brain slice recordings can characterize epileptic mechanisms in a simpler, more controlled preparation than in vivo. Yet, the intrinsic hyper-excitability of a chronic epileptic focus may not be entirely preserved in slices following the severing of connections in slice preparation. This study utilizes recordings of multiple electrode arrays to characterize which features of epileptic hyper-excitability present in in vivo chronic adult neocortical epileptic foci are preserved in brain slices. After tetanus toxin somatosensory cortex injections, adult rats manifest chronic spontaneous epileptic discharges both in the injection site (primary focus) and in the contralateral side (secondary focus). We prepared neocortical slices from these epileptic animals. When perfused with 4-Aminopyridine in a magnesium free medium, epileptic rat slices exhibit higher voltage discharges and broader spreading than control rat slices. Rates of discharges are similar in slices of epileptic and normal rats, however. Ictal and interictal discharges are distributed over most cortical layers, though with significant differences between primary and secondary foci. A chronic neocortical epileptic focus in slices does not show increased spontaneous pacemakers initiating epileptic discharges but shows discharges with higher voltages and broader spread, consistent with an enhanced synchrony of cellular and synaptic generators over wider surfaces. PMID:26892299

  7. Epileptic seizures: Quakes of the brain?

    NASA Astrophysics Data System (ADS)

    Osorio, Ivan; Frei, Mark G.; Sornette, Didier; Milton, John; Lai, Ying-Cheng

    2010-08-01

    A dynamical analogy supported by five scale-free statistics (the Gutenberg-Richter distribution of event sizes, the distribution of interevent intervals, the Omori and inverse Omori laws, and the conditional waiting time until the next event) is shown to exist between two classes of seizures (“focal” in humans and generalized in animals) and earthquakes. Increments in excitatory interneuronal coupling in animals expose the system’s dependence on this parameter and its dynamical transmutability: moderate increases lead to power-law behavior of seizure energy and interevent times, while marked ones to scale-free (power-law) coextensive with characteristic scales and events. The coextensivity of power law and characteristic size regimes is predicted by models of coupled heterogeneous threshold oscillators of relaxation and underscores the role of coupling strength in shaping the dynamics of these systems.

  8. The contribution of raised intraneuronal chloride to epileptic network activity.

    PubMed

    Alfonsa, Hannah; Merricks, Edward M; Codadu, Neela K; Cunningham, Mark O; Deisseroth, Karl; Racca, Claudia; Trevelyan, Andrew J

    2015-05-20

    Altered inhibitory function is an important facet of epileptic pathology. A key concept is that GABAergic activity can become excitatory if intraneuronal chloride rises. However, it has proved difficult to separate the role of raised chloride from other contributory factors in complex network phenomena, such as epileptic pathology. Therefore, we asked what patterns of activity are associated with chloride dysregulation by making novel use of Halorhodopsin to load clusters of mouse pyramidal cells artificially with Cl(-). Brief (1-10 s) activation of Halorhodopsin caused substantial positive shifts in the GABAergic reversal potential that were proportional to the charge transfer during the illumination and in adult neocortical pyramidal neurons decayed with a time constant of τ = 8.0 ± 2.8s. At the network level, these positive shifts in EGABA produced a transient rise in network excitability, with many distinctive features of epileptic foci, including high-frequency oscillations with evidence of out-of-phase firing (Ibarz et al., 2010). We show how such firing patterns can arise from quite small shifts in the mean intracellular Cl(-) level, within heterogeneous neuronal populations. Notably, however, chloride loading by itself did not trigger full ictal events, even with additional electrical stimulation to the underlying white matter. In contrast, when performed in combination with low, subepileptic levels of 4-aminopyridine, Halorhodopsin activation rapidly induced full ictal activity. These results suggest that chloride loading has at most an adjunctive role in ictogenesis. Our simulations also show how chloride loading can affect the jitter of action potential timing associated with imminent recruitment to an ictal event (Netoff and Schiff, 2002). PMID:25995461

  9. The Contribution of Raised Intraneuronal Chloride to Epileptic Network Activity

    PubMed Central

    Alfonsa, Hannah; Merricks, Edward M.; Codadu, Neela K.; Cunningham, Mark O.; Deisseroth, Karl; Racca, Claudia

    2015-01-01

    Altered inhibitory function is an important facet of epileptic pathology. A key concept is that GABAergic activity can become excitatory if intraneuronal chloride rises. However, it has proved difficult to separate the role of raised chloride from other contributory factors in complex network phenomena, such as epileptic pathology. Therefore, we asked what patterns of activity are associated with chloride dysregulation by making novel use of Halorhodopsin to load clusters of mouse pyramidal cells artificially with Cl−. Brief (1–10 s) activation of Halorhodopsin caused substantial positive shifts in the GABAergic reversal potential that were proportional to the charge transfer during the illumination and in adult neocortical pyramidal neurons decayed with a time constant of τ = 8.0 ± 2.8s. At the network level, these positive shifts in EGABA produced a transient rise in network excitability, with many distinctive features of epileptic foci, including high-frequency oscillations with evidence of out-of-phase firing (Ibarz et al., 2010). We show how such firing patterns can arise from quite small shifts in the mean intracellular Cl− level, within heterogeneous neuronal populations. Notably, however, chloride loading by itself did not trigger full ictal events, even with additional electrical stimulation to the underlying white matter. In contrast, when performed in combination with low, subepileptic levels of 4-aminopyridine, Halorhodopsin activation rapidly induced full ictal activity. These results suggest that chloride loading has at most an adjunctive role in ictogenesis. Our simulations also show how chloride loading can affect the jitter of action potential timing associated with imminent recruitment to an ictal event (Netoff and Schiff, 2002). PMID:25995461

  10. Perirhinal Cortex Hyperexcitability in Pilocarpine-Treated Epileptic Rats

    PubMed Central

    Benini, Ruba; Longo, Daniela; Biagini, Giuseppe; Avoli, Massimo

    2016-01-01

    The perirhinal cortex (PC), which is heavily connected with several epileptogenic regions of the limbic system such as the entorhinal cortex and amygdala, is involved in the generation and spread of seizures. However, the functional alterations occurring within an epileptic PC network are unknown. Here, we analyzed this issue by using in vitro electrophysiology and immunohistochemistry in brain tissue obtained from pilocarpine-treated epileptic rats and age-matched, nonepileptic controls (NECs). Neurons recorded intracellularly from the PC deep layers in the two experimental groups had similar intrinsic and firing properties and generated spontaneous depolarizing and hyperpolarizing postsynaptic potentials with comparable duration and amplitude. However, spontaneous and stimulus-induced epileptiform discharges were seen with field potential recordings in over one-fifth of pilocarpine-treated slices but never in NEC tissue. These network events were reduced in duration by antagonizing NMDA receptors and abolished by NMDA + non-NMDA glutamatergic receptor antagonists. Pharmacologically isolated isolated inhibitory postsynaptic potentials had reversal potentials for the early GABAA receptor-mediated component that were significantly more depolarized in pilocarpine-treated cells. Experiments with a potassium-chloride cotransporter 2 antibody identified, in pilocarpine-treated PC, a significant immunostaining decrease that could not be explained by neuronal loss. However, interneurons expressing parvalbumin and neuropeptide Y were found to be decreased throughout the PC, whereas cholecystokinin-positive cells were diminished in superficial layers. These findings demonstrate synaptic hyper-excitability that is contributed by attenuated inhibition in the PC of pilocarpine-treated epileptic rats and underscore the role of PC networks in temporal lobe epilepsy. PMID:20865722

  11. Detection of Epileptic Seizure Using Wireless Sensor Networks

    PubMed Central

    Borujeny, Golshan Taheri; Yazdi, Mehran; Keshavarz-Haddad, Alireza; Borujeny, Arash Rafie

    2013-01-01

    The monitoring of epileptic seizures is mainly done by means of electroencephalogram (EEG) monitoring. Although this method is accurate, it is not comfortable for the patient as the EEG-electrodes have to be attached to the scalp which hampers the patient's movement. This makes long-term home monitoring not feasible. In this paper, the aim is to propose a seizure detection system based on accelerometry for the detection of epileptic seizure. The used sensors are wireless, which can improve quality of life for the patients. In this system, three 2D accelerometer sensors are positioned on the right arm, left arm, and left thigh of an epileptic patient. Datasets from three patients suffering from severe epilepsy are used in this paper for the development of an automatic detection algorithm. This monitoring system is based on Wireless Sensor Networks and can determine the location of the patient when a seizure is detected and then send an alarm to hospital staff or the patient's relatives. Our wireless sensor nodes are MICAz Motes developed by Crossbow Technology. The proposed system can be used for patients living in a clinical environment or at their home, where they do only their daily routines. The analysis of the recorded data is done by an Artificial Neural Network and K Nearest-Neighbor to recognize seizure movements from normal movements. The results show that K Nearest Neighbor performs better than Artificial Neural Network for detecting these seizures. The results also show that if at least 50% of the signal consists of seizure samples, we can detect the seizure accurately. In addition, there is no need for training the algorithm for each new patient. PMID:24098859

  12. Epileptic spasms without hypsarrhythmia in infancy and childhood: tonic spasms as a seizure type.

    PubMed

    Marchi, Luciana R De; Seraphim, Evelyn A; Corso, Jeana T; Naves, Pedro Vf; Carvalho, Kelly Cristina de; Ramirez, Milton David H; Ferrari-Marinho, Taissa; Guaranha, Mirian Sb; Yacubian, Elza Márcia T

    2015-06-01

    Epileptic spasms were defined by the International League Against Epilepsy Task Force on Classification and Terminology in 2001 as a specific seizure type. Epileptic spasms without hypsarrhythmia have been described in some series of patients, occurring either in infancy or childhood. More prolonged epileptic spasms without hypsarrhythmia were previously defined as a different seizure type, and referred to as "tonic spasm seizures". Here, we present a 5-year-old boy who started having epileptic spasms without hypsarrhythmia at 8 months of age, effectively treated with oxcarbazepine. With the withdrawal of medication, epileptic spasms returned. Video-EEG monitoring revealed high-voltage slow waves superimposed by low-voltage fast activity, followed by an electrodecremental phase and a burst of asymmetric fast activity, time-locked to clinical tonic spasm seizures. Brain MRI showed left temporal atrophy with temporal pole grey/white matter junction blurring and ictal PET-CT showed left basal frontal hypermetabolism. Seizures were refractory to several AEDs and vigabatrin was introduced with seizure cessation. Despite efforts to classify epileptic spasms, these are still considered as part of the group of unknown seizure types. In some cases, a focal origin has been suggested, leading to the term "periodic spasms" and "focal spasms". In this case, epileptic spasms without hypsarrhythmia, associated with tonic spasms, may be a variant of focal spasms and might be considered as an epileptic syndrome. [Published with video sequence]. PMID:25895540

  13. Defective auditory processing in a child with temporal epileptic focus.

    PubMed

    Shuper, Avinoam; Medvedovsky, Mordechai; Kivity, Sara

    2015-03-01

    A 9-year-old boy presented with intolerance to noise that was a trigger for violent temper tantrums that occasionally resembled complex partial seizures. The condition was also a cause for withdrawal from all activities and settings that could potentially be associated with noise. Both electroencephalography and magnetoencephalography clearly demonstrated a left temporal (T5) epileptic focus, although the child never had convulsive seizures. Genetic studies failed to reveal a GRIN2A mutation. We suggest that the hyperacusis in the reported child is another variation of the Landau-Kleffner spectrum. PMID:24789517

  14. Stimulus-induced reflex epileptic spasms in 5p- syndrome.

    PubMed

    Shirai, Kentaro; Saito, Yoshiaki; Yokoyama, Atushi; Nishimura, Yoko; Tamasaki, Akiko; Maegaki, Yoshihiro

    2016-02-01

    Here we describe two patients with 5p- syndrome who suffered from epilepsy characterised by stimulus-induced epileptic spasms manifesting as head nodding. In patient 1, a series of spasms were exclusively triggered by eating, and were associated with diffuse high-voltage slow waves on ictal EEG, particularly presenting as a positive slow potential at the left mid-temporal area. Clusters of sharp waves with negative polarity emerged in the same area during the inter-spasm periods during eating. In patient 2, spasms were provoked by either eating or micturition. Ictal EEG of clustered spasms after micturition showed positive slow or triphasic waves, which correlated with each spasm, over the bifrontal and vertex areas. These findings suggest that the focal cortical areas act as trigger regions in reflex epilepsies, and that a spasm-generator responsible for the execution of reflex spasms exists either in other cortical areas or in the subcortical structures. Although epilepsy is an unusual complication of 5p- syndrome, this syndrome may have a propensity to develop reflex epilepsy, particularly epileptic spasms. However, identification of responsible genes and their roles in this phenotype requires further investigations. PMID:26298410

  15. The quantitative measurement of consciousness during epileptic seizures.

    PubMed

    Nani, Andrea; Cavanna, Andrea E

    2014-01-01

    The assessment of consciousness is a fundamental element in the classification of epileptic seizures. It is, therefore, of great importance for clinical practice to develop instruments that enable an accurate and reliable measurement of the alteration of consciousness during seizures. Over the last few years, three psychometric scales have been specifically proposed to measure ictal consciousness: the Ictal Consciousness Inventory (ICI), the Consciousness Seizure Scale (CSS), and the Responsiveness in Epilepsy Scale--versions I and II (RES-I and RES-II). The ICI is a self-report psychometric instrument which retrospectively assesses ictal consciousness along the dimensions of the level/arousal and contents/awareness. The CSS has been used by clinicians to quantify the impairment of consciousness in order to establish correlations with the brain mechanisms underlying alterations of consciousness during temporal lobe seizures. The most recently developed observer-rated instrument is the RES-I, which has been used to assess responsiveness during epileptic seizures in patients undergoing video-EEG. The implementation of standardized psychometric tools for the assessment of ictal consciousness can complement clinical observations and contribute to improve accuracy in seizure classification. PMID:24113569

  16. Are brief or recurrent transient global amnesias of epileptic origin?

    PubMed Central

    Melo, T P; Ferro, J M; Paiva, T

    1994-01-01

    To evaluate if short (less than one hour) or recurrent, or both, episodes of transient global amnesia (TGA) have an epileptic origin or carry a subsequent risk of epilepsy a group of patients with these types of TGA attacks was studied. The group was selected from a prospective series of 103 patients with TGA. Sixteen patients had an episode lasting less than one hour, 13 had more than one episode, and five patients had both short and recurrent attacks. For each patient the number of recurrences was small (four or less) and they were separated by months or years. During short attacks of TGA many subjects showed other typical features of TGA including repeated questioning (12 subjects) and performance of purposeful complex acts (eight subjects). Twelve short attacks were closely related to a characteristic precipitating event. During follow up only one patient had a seizure (partial motor). No other association between either short or repeated attacks of TGA and past history of epilepsy or paroxysmal discharges were seen on the EEG. Short or recurrent, or both, attacks of TGA are not epileptic and do not carry a relevant risk of subsequent seizures. Images PMID:8201337

  17. Epileptic Neuronal Networks: Methods of Identification and Clinical Relevance

    PubMed Central

    Stefan, Hermann; Lopes da Silva, Fernando H.

    2012-01-01

    The main objective of this paper is to examine evidence for the concept that epileptic activity should be envisaged in terms of functional connectivity and dynamics of neuronal networks. Basic concepts regarding structure and dynamics of neuronal networks are briefly described. Particular attention is given to approaches that are derived, or related, to the concept of causality, as formulated by Granger. Linear and non-linear methodologies aiming at characterizing the dynamics of neuronal networks applied to EEG/MEG and combined EEG/fMRI signals in epilepsy are critically reviewed. The relevance of functional dynamical analysis of neuronal networks with respect to clinical queries in focal cortical dysplasias, temporal lobe epilepsies, and “generalized” epilepsies is emphasized. In the light of the concepts of epileptic neuronal networks, and recent experimental findings, the dichotomic classification in focal and generalized epilepsy is re-evaluated. It is proposed that so-called “generalized epilepsies,” such as absence seizures, are actually fast spreading epilepsies, the onset of which can be tracked down to particular neuronal networks using appropriate network analysis. Finally new approaches to delineate epileptogenic networks are discussed. PMID:23532203

  18. Studying Network Mechanisms Using Intracranial Stimulation in Epileptic Patients

    PubMed Central

    David, Olivier; Bastin, Julien; Chabardès, Stéphan; Minotti, Lorella; Kahane, Philippe

    2010-01-01

    Patients suffering from focal drug-resistant epilepsy who are explored using intracranial electrodes allow to obtain data of exceptional value for studying brain dynamics in correlation with pathophysiological and cognitive processes. Direct electrical stimulation (DES) of cortical regions and axonal tracts in those patients elicits a number of very specific perceptual or behavioral responses, but also abnormal responses due to specific configurations of epileptic networks. Here, we review how anatomo-functional brain connectivity and epilepsy network mechanisms can be assessed from DES responses measured in patients. After a brief summary of mechanisms of action of brain electrical stimulation, we recall the conceptual framework for interpreting DES results in the context of brain connectivity and review how DES can be used for the characterization of functional networks, the identification of the seizure onset zone, the study of brain plasticity mechanisms, and the anticipation of epileptic seizures. This pool of exceptional data may be underexploited by fundamental research on brain connectivity and leaves much to be learned. PMID:21060722

  19. Clonazepam oral droplets for the treatment of acute epileptic seizures.

    PubMed

    Sakata, Osamu; Onishi, Hiraku; Machida, Yoshiharu

    2008-12-01

    Oral droplet formulations of clonazepam (CZ) were developed to examine their potentials as an alternative to i.v. administration for the treatment of acute epileptic seizures. Propylene glycol containing 2.5% (wt/wt) CZ with or without 5.0% (wt/wt) oleic acid (OA) was prepared as a solution by heating at 90 degrees C and subsequently lowering the temperature to 30 degrees C. The droplet (20 microL) was administered to the oral cavity between the lower gum and bottom lip before CZ precipitation started. With a droplet of propylene glycol loaded with 2.5% (wt/wt) CZ and 5.0% (wt/wt) OA, the plasma concentration reached 20 ng/mL (minimal effective concentration) within 10 min and was maintained between 20 and 60 ng/mL, less than a toxic level, for a period of 60 min. For a droplet of propylene glycol loaded only with CZ at 2.5% (wt/wt), it took more than 15 min for the plasma concentration to reach 20 ng/mL. It is suggested that a droplet of CZ/OA/propylene glycol (2.5:5.0:92.5, wt/wt) might be useful as an alternative to i.v. injection of CZ for the treatment of acute epileptic seizures. PMID:18720141

  20. How does the hippocampus shape decisions?

    PubMed

    Palombo, Daniela J; Keane, Margaret M; Verfaellie, Mieke

    2015-11-01

    Making optimal decisions depends on an appreciation of the value of choices. An important source of information about value comes from memory for prior experience. Such value-based learning has historically been considered the domain of a striatal memory system. However, recent developments suggest that memorial representations supported by the hippocampus may also contribute to decision making. Unlike striatal representations, hippocampal ones are flexible; they can be modified and updated as new information is acquired. In this paper we argue that the hippocampus plays a pivotal role in value-based decision making via three flexible learning mechanisms: (1) updating, (2) generalization, and (3) construction. PMID:26297967

  1. Absence epileptic activity changing effects of non-adenosine nucleoside inosine, guanosine and uridine in Wistar Albino Glaxo Rijswijk rats.

    PubMed

    Kovács, Z; Kékesi, K A; Dobolyi, Á; Lakatos, R; Juhász, G

    2015-08-01

    Adenosine (Ado) and non-adenosine (non-Ado) nucleosides such as inosine (Ino), guanosine (Guo) and uridine (Urd) may have regionally different roles in the regulation of physiological and pathophysiological processes in the central nervous system (CNS) such as epilepsy. It was demonstrated previously that Ino and Guo decreased quinolinic acid (QA)-induced seizures and Urd reduced penicillin-, bicuculline- and pentylenetetrazole (PTZ)-induced seizures. It has also been demonstrated that Ino and Urd may exert their effects through GABAergic system by altering the function of GABA(A) type of gamma-aminobutyric acid receptors (GABAA receptors) whereas Guo decreases glutamate-induced excitability through glutamatergic system, which systems (GABAergic and glutamatergic) are involved in pathomechanisms of absence epilepsy. Thus, we hypothesized that Ino and Guo, similarly to the previously described effect of Urd, might also decrease absence epileptic activity. We investigated in the present study whether intraperitoneal (i.p.) application of Ino (500 and 1000mg/kg), Guo (20 and 50mg/kg), Urd (500 and 1000mg/kg), GABA(A) receptor agonist muscimol (1 and 3mg/kg), GABA(A) receptor antagonist bicuculline (2 and 4mg/kg), non-selective Ado receptor antagonist theophylline (5 and 10mg/kg) and non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine maleate (MK-801, 0.0625 and 0.1250mg/kg) alone and in combination have modulatory effects on absence epileptic activity in Wistar Albino Glaxo Rijswijk (WAG/Rij) rats. We found that Guo decreased the number of spike-wave discharges (SWDs) whereas Ino increased it dose-dependently. We strengthened that Urd can decrease absence epileptic activity. Our results suggest that Guo, Urd and their analogs could be potentially effective drugs for treatment of human absence epilepsy. PMID:26037802

  2. Stress effects on the hippocampus: a critical review

    PubMed Central

    Kim, Eun Joo; Pellman, Blake

    2015-01-01

    Uncontrollable stress has been recognized to influence the hippocampus at various levels of analysis. Behaviorally, human and animal studies have found that stress generally impairs various hippocampal-dependent memory tasks. Neurally, animal studies have revealed that stress alters ensuing synaptic plasticity and firing properties of hippocampal neurons. Structurally, human and animal studies have shown that stress changes neuronal morphology, suppresses neuronal proliferation, and reduces hippocampal volume. Since the inception of stress research nearly 80 years ago, much focus has been on the varying levels of hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine hormones, namely glucocorticoids, as mediators of the myriad stress effects on the hippocampus and as contributing factors to stress-associated psychopathologies such as post-traumatic stress disorder (PTSD). However, reports of glucocorticoid-produced alterations in hippocampal functioning vary widely across studies. This review provides a brief history of stress research, examines how the glucocorticoid hypothesis emerged and guides contemporary stress research, and considers alternative approaches to understanding the mechanisms underlying stress effects on hippocampal functioning. PMID:26286651

  3. Hidden pattern discovery on epileptic EEG with 1-D local binary patterns and epileptic seizures detection by grey relational analysis.

    PubMed

    Kaya, Yılmaz

    2015-09-01

    This paper proposes a novel approach to detect epilepsy seizures by using Electroencephalography (EEG), which is one of the most common methods for the diagnosis of epilepsy, based on 1-Dimension Local Binary Pattern (1D-LBP) and grey relational analysis (GRA) methods. The main aim of this paper is to evaluate and validate a novel approach, which is a computer-based quantitative EEG analyzing method and based on grey systems, aimed to help decision-maker. In this study, 1D-LBP, which utilizes all data points, was employed for extracting features in raw EEG signals, Fisher score (FS) was employed to select the representative features, which can also be determined as hidden patterns. Additionally, GRA is performed to classify EEG signals through these Fisher scored features. The experimental results of the proposed approach, which was employed in a public dataset for validation, showed that it has a high accuracy in identifying epileptic EEG signals. For various combinations of epileptic EEG, such as A-E, B-E, C-E, D-E, and A-D clusters, 100, 96, 100, 99.00 and 100% were achieved, respectively. Also, this work presents an attempt to develop a new general-purpose hidden pattern determination scheme, which can be utilized for different categories of time-varying signals. PMID:26206400

  4. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

    PubMed Central

    Varela-Nallar, Lorena; Arredondo, Sebastian B.; Tapia-Rojas, Cheril; Hancke, Juan; Inestrosa, Nibaldo C.

    2015-01-01

    Andrographolide (ANDRO) is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO is a competitive inhibitor of glycogen synthase kinase-3β (GSK-3β), a key enzyme of the Wnt/β-catenin signaling cascade. Since this signaling pathway regulates neurogenesis in the adult hippocampus, we evaluated whether ANDRO stimulates this process. Treatment with ANDRO increased neural progenitor cell proliferation and the number of immature neurons in the hippocampus of 2- and 10-month-old mice compared to age-matched control mice. Moreover, ANDRO stimulated neurogenesis increasing the number of newborn dentate granule neurons. Also, the effect of ANDRO was evaluated in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease. In these mice, ANDRO increased cell proliferation and the density of immature neurons in the dentate gyrus. Concomitantly with the increase in neurogenesis, ANDRO induced the activation of the Wnt signaling pathway in the hippocampus of wild-type and APPswe/PS1ΔE9 mice determined by increased levels of β-catenin, the inactive form of GSK-3β, and NeuroD1, a Wnt target gene involved in neurogenesis. Our findings indicate that ANDRO stimulates neurogenesis in the adult hippocampus suggesting that this drug could be used as a therapy in diseases in which neurogenesis is affected. PMID:26798521

  5. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus.

    PubMed

    Varela-Nallar, Lorena; Arredondo, Sebastian B; Tapia-Rojas, Cheril; Hancke, Juan; Inestrosa, Nibaldo C

    2015-01-01

    Andrographolide (ANDRO) is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO is a competitive inhibitor of glycogen synthase kinase-3β (GSK-3β), a key enzyme of the Wnt/β-catenin signaling cascade. Since this signaling pathway regulates neurogenesis in the adult hippocampus, we evaluated whether ANDRO stimulates this process. Treatment with ANDRO increased neural progenitor cell proliferation and the number of immature neurons in the hippocampus of 2- and 10-month-old mice compared to age-matched control mice. Moreover, ANDRO stimulated neurogenesis increasing the number of newborn dentate granule neurons. Also, the effect of ANDRO was evaluated in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease. In these mice, ANDRO increased cell proliferation and the density of immature neurons in the dentate gyrus. Concomitantly with the increase in neurogenesis, ANDRO induced the activation of the Wnt signaling pathway in the hippocampus of wild-type and APPswe/PS1ΔE9 mice determined by increased levels of β-catenin, the inactive form of GSK-3β, and NeuroD1, a Wnt target gene involved in neurogenesis. Our findings indicate that ANDRO stimulates neurogenesis in the adult hippocampus suggesting that this drug could be used as a therapy in diseases in which neurogenesis is affected. PMID:26798521

  6. Neural Stem Cell or Human Induced Pluripotent Stem Cell-Derived GABA-ergic Progenitor Cell Grafting in an Animal Model of Chronic Temporal Lobe Epilepsy.

    PubMed

    Upadhya, Dinesh; Hattiangady, Bharathi; Shetty, Geetha A; Zanirati, Gabriele; Kodali, Maheedhar; Shetty, Ashok K

    2016-01-01

    Grafting of neural stem cells (NSCs) or GABA-ergic progenitor cells (GPCs) into the hippocampus could offer an alternative therapy to hippocampal resection in patients with drug-resistant chronic epilepsy, which afflicts >30% of temporal lobe epilepsy (TLE) cases. Multipotent, self-renewing NSCs could be expanded from multiple regions of the developing and adult brain, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). On the other hand, GPCs could be generated from the medial and lateral ganglionic eminences of the embryonic brain and from hESCs and hiPSCs. To provide comprehensive methodologies involved in testing the efficacy of transplantation of NSCs and GPCs in a rat model of chronic TLE, NSCs derived from the rat medial ganglionic eminence (MGE) and MGE-like GPCs derived from hiPSCs are taken as examples in this unit. The topics comprise description of the required materials, reagents and equipment, methods for obtaining rat MGE-NSCs and hiPSC-derived MGE-like GPCs in culture, generation of chronically epileptic rats, intrahippocampal grafting procedure, post-grafting evaluation of the effects of grafts on spontaneous recurrent seizures and cognitive and mood impairments, analyses of the yield and the fate of graft-derived cells, and the effects of grafts on the host hippocampus. © 2016 by John Wiley & Sons, Inc. PMID:27532817

  7. Genetic investigations of the epileptic encephalopathies: Recent advances.

    PubMed

    Myers, C T; Mefford, H C

    2016-01-01

    The epileptic encephalopathies (EEs) are a group of epilepsy syndromes characterized by multiple seizure types, abundant epileptiform activity, and developmental delay or regression. Advances in genomic technologies over the past decade have accelerated our understanding of the genetic etiology of EE, which is largely due to de novo mutations. Chromosome microarrays to detect copy number variants identify a genomic cause in at least 5-10% of cases. Next-generation sequencing in the form of gene panels or whole exome sequencing have highlighted the role of de novo sequence changes and revealed extensive genetic heterogeneity. The novel gene discoveries in EE implicate diverse cellular pathways including chromatin remodeling, transcriptional regulation, and mTOR regulation in the etiology of epilepsy, highlighting new targets for potential therapeutic intervention. In this chapter, we discuss the rapid pace of gene discovery in EE facilitated by genomic technologies and highlight several novel genes and potential therapies. PMID:27323938

  8. Compulsive versifying after treatment of transient epileptic amnesia

    PubMed Central

    Woollacott, Ione O. C.; Fletcher, Phillip D.; Massey, Luke A.; Pasupathy, Amirtha; Rossor, Martin N.; Caine, Diana; Rohrer, Jonathan D.; Warren, Jason D.

    2015-01-01

    Compulsive production of verse is an unusual form of hypergraphia that has been reported mainly in patients with right temporal lobe seizures. We present a patient with transient epileptic amnesia and a left temporal seizure focus, who developed isolated compulsive versifying, producing multiple rhyming poems, following seizure cessation induced by lamotrigine. Functional neuroimaging studies in the healthy brain implicate left frontotemporal areas in generating novel verbal output and rhyme, while dysregulation of neocortical and limbic regions occurs in temporal lobe epilepsy. This case complements previous observations of emergence of altered behavior with reduced seizure frequency in patients with temporal lobe epilepsy. Such cases suggest that reduced seizure frequency has the potential not only to stabilize or improve memory function, but also to trigger complex, specific behavioral alterations. PMID:25157425

  9. On the pathogenesis of epileptic and hysterical seizures

    PubMed Central

    Krapf, E. E.

    1957-01-01

    In discussing the problem of differentiating between epileptic and hysterical seizures, the author maintains that electroencephalographic and psychosomatic research indicates that all “epileptiform” seizures are the outcome of a constant interplay of stress and predisposition in which both these factors are of a polygenetic origin. He points out that behind these reactions manifested in consciousness and motility, there lies a fundamental function of defence and that the nature of the seizures occurring is decided by the level of physiogenic or psychogenic regression which prevails in different cases, and which is to a great extent codetermined by a complementary “inviting” level of physical and psychical subevolution (lack of maturation). He holds that the pathogenesis of “epileptiform” seizures is of a truly psychosomatic nature and that this circumstance should be reflected in the therapeutic approach to these disorders. PMID:13472429

  10. Fast Fourier transformation analysis of kindling-induced afterdischarge in the rabbit hippocampus.

    PubMed

    Tsuchiya, Komei; Kogure, Shinichi

    2011-06-01

    Kindling is a widely used animal model of intractable temporal lobe epilepsy. In the present study, we performed fast Fourier transformation (FFT) analysis of kindling-induced afterdischarge (AD) in the rabbit hippocampus. Ten adult rabbits were used. Kindling stimulation to the right hippocampus was delivered as a train of biphasic pulses (1 ms duration each) of 50 Hz for 1s, with suprathreshold intensity for AD. Motor responses were classified into five stages according to the conventional criteria. Of 10 animals, five developed stage 5 convulsions with a mean of 21 stimulations (kindled (K) group), while the remaining five animals did not (incomplete kindling (IK) group). We standardized each ratio of power spectral density of lower frequency band component (LFB: 0-9 Hz) and the higher frequency band (HFB: 12-30 Hz) in the initial stage as 1.0. The IK group exhibited small decrements (0.99 and 0.94 times) in LFB and HFB components at the final stage. In contrast, the K group exhibited a significantly (p<0.05) large decrement (0.49 times) in the LFB component and a very large increment (4.45 times) of HFB component at the final stage. Correlation analyses were performed between alteration of power spectral density ratio of the HFB component and AD duration, interictal discharge frequency, and behavioral stage during kindling progression. Fairly strong positive correlations were found in all cases in the K group. FFT analysis of kindling-induced AD demonstrated an important role of the HFB component: enhancement of the HFB component is associated with kindled stage, while decrement of it is associated with incomplete kindling stage. These findings suggest that FFT analysis of stimulus-induced and spontaneous seizure discharges is useful for examination of the progression of epileptic disorders. PMID:21498048

  11. Clinical and electrographic findings in epileptic vertigo and dizziness

    PubMed Central

    Lee, Seung-Han; Robinson, Karen A.; Kaplan, Peter W.; Newman-Toker, David E.

    2015-01-01

    Objective: Seizures can cause vestibular symptoms, even without obvious epileptic features. We sought to characterize epileptic vertigo or dizziness (EVD) to improve differentiation from nonepileptic causes, particularly when vestibular symptoms are the sole manifestation. Methods: We conducted a systematic review with electronic (Medline) and manual search for English-language studies (1955–2014). Two independent reviewers selected studies. Study/patient characteristics were abstracted. We defined 3 study population types: (1) seizures, some experiencing vertigo/dizziness (disease cohort); (2) vertigo/dizziness, some due to seizures (symptom cohort); (3) vertigo/dizziness due to seizures in all patients (EVD-only cohort). Results: We identified 84 studies describing 11,354 patients (disease cohort = 8,129; symptom cohort = 2,965; EVD-only cohort = 260). Among 1,055 EVD patients in whom a distinction could be made, non-isolated EVD was present in 8.5%, isolated EVD in 0.8%. Thorough diagnostic workups (ictal EEG, vestibular testing, and brain MRI to exclude other causes) were rare (<0.1%). Ictal EEG was reported in 487 (4.3%), formal neuro-otologic assessment in 1,107 (9.7%). Localized EEG abnormalities (n = 350) were most frequently temporal (79.8%) and uncommonly parietal (11.8%). Duration of episodic vestibular symptoms varied, but was very brief (<30 seconds) in 69.6% of isolated EVD and 6.9% of non-isolated EVD. Conclusions: Non-isolated EVD is much more prevalent than isolated EVD, which appears to be rare. Diagnostic evaluations for EVD are often incomplete. EVD is primarily associated with temporal lobe seizures; whether this reflects greater epidemiologic prevalence of temporal lobe seizures or a tighter association with dizziness/vertigo presentations than with other brain regions remains unknown. Consistent with clinical wisdom, isolated EVD spells often last just seconds, although many patients experience longer spells. PMID:25795644

  12. Are The Dorsal and Ventral Hippocampus functionally distinct structures?

    PubMed Central

    Fanselow, Michael S.; Dong, Hong-Wei

    2009-01-01

    One literature treats the hippocampus as a purely cognitive structure involved in memory; another treats it as a regulator of emotion whose dysfunction leads to psychopathology. We review behavioral, anatomical, and gene expression studies that together support a functional segmentation into 3 hippocampal compartments dorsal, intermediate and ventral. The dorsal hippocampus, which corresponds to the posterior hippocampus in primates, performs primarily cognitive functions. The ventral (anterior in primates) relates to stress, emotion and affect. Strikingly, gene expression in the dorsal hippocampus correlates with cortical regions involved in information processing, while genes expressed in the ventral hippocampus correlate with regions involved in emotion and stress (amygdala and hypothalamus). PMID:20152109

  13. The hippocampus and the flexible use and processing of language

    PubMed Central

    Duff, Melissa C.; Brown-Schmidt, Sarah

    2012-01-01

    Fundamental to all human languages is an unlimited expressive capacity and creative flexibility that allow speakers to rapidly generate novel and complex utterances. In turn, listeners interpret language “on-line,” incrementally integrating multiple sources of information as words unfold over time. A challenge for theories of language processing has been to understand how speakers and listeners generate, gather, integrate, and maintain representations in service of language processing. We propose that many of the processes by which we use language place high demands on and receive contributions from the hippocampal declarative memory system. The hippocampal declarative memory system is long known to support relational binding and representational flexibility. Recent findings demonstrate that these same functions are engaged during the real-time processes that support behavior in-the-moment. Such findings point to the hippocampus as a potentially key contributor to cognitive functions that require on-line integration of multiple sources of information, such as on-line language processing. Evidence supporting this view comes from findings that individuals with hippocampal amnesia show deficits in the use of language flexibly and on-line. We conclude that the relational binding and representational flexibility afforded by the hippocampal declarative memory system positions the hippocampus as a key contributor to language use and processing. PMID:22493573

  14. Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2).

    PubMed

    Saitsu, Hirotomo; Osaka, Hitoshi; Sugiyama, Shirou; Kurosawa, Kenji; Mizuguchi, Takeshi; Nishiyama, Kiyomi; Nishimura, Akira; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Harada, Naoki; Kato, Mitsuhiro; Matsumoto, Naomichi

    2012-01-01

    We report on a female patient with early infantile epileptic encephalopathy and severe psychomotor disability possessing a de novo balanced translocation t(1;9)(q32;q13). The patient showed clonic convulsions of extremities 2 days after birth. Electroencephalogram (EEG) transiently showed atypical suppression-burst pattern. The seizures evolved to brief tonic spasms, and hypsarrhythmia on EEG was noticed at age of 5 months, indicating the transition to West syndrome. By using fluorescent in situ hybridization (FISH), southern hybridization, and inverse PCR, the translocation breakpoints were successfully determined at the nucleotide level. The 1q32.1 breakpoint was located within a segmental duplication and disrupted the gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2). The 9q13 breakpoint was suggested to reside in the heterochromatin region. Srgap2 has been shown to be specifically expressed in developing brain of rodents, negatively regulate neuronal migration and induce neurite outgrowth and branching. Thus, SRGAP2 is very likely to play a role in the developing human brain. This is a first report of the SRGAP2 abnormality associated with early infantile epileptic encephalopathy. PMID:22106086

  15. First records of Hippocampus algiricus in the Canary Islands (north-east Atlantic Ocean) with an observation of hybridization with Hippocampus hippocampus.

    PubMed

    Otero-Ferrer, F; Herrera, R; López, A; Socorro, J; Molina, L; Bouza, C

    2015-10-01

    Morphometric and genetic analyses confirmed the first records of the West African seahorse Hippocampus algiricus at Gran Canaria Island (north-east Atlantic Ocean), and also the first evidence of interspecific hybridization in seahorses. These results provide additional data on the distribution of H. algiricus that may help to establish future conservation strategies, and uncover a new potential sympatric scenario between H. algiricus and Hippocampus hippocampus. PMID:26365616

  16. Linear aspects of transformation from interictal epileptic discharges to BOLD fMRI signals in an animal model of occipital epilepsy.

    PubMed

    Mirsattari, Seyed M; Wang, Zheng; Ives, John R; Bihari, Frank; Leung, L Stan; Bartha, Robert; Menon, Ravi S

    2006-05-01

    Epileptic disorders manifest with seizures and interictal epileptic discharges (IEDs). The hemodynamic changes that accompany IEDs are poorly understood and may be critical for understanding epileptogenesis. Despite a known linear coupling of the neurovascular elements in normal brain tissues, previous simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) studies have shown variable correlations between epileptic discharges and blood oxygenation level-dependent (BOLD) response, partly because most previous studies assumed particular hemodynamic properties in normal brain tissue. The occurrence of IEDs in human subjects is unpredictable. Therefore, an animal model with reproducible stereotyped IEDs was developed by the focal injection of penicillin into the right occipital cortex of rats anesthetized with isoflurane. Simultaneous EEG-fMRI was used to study the hemodynamic changes during IEDs. A hybrid of temporal independent component analysis (ICA) of EEG and spatial ICA of fMRI data was used to correlate BOLD fMRI signals with IEDs. A linear autoregression with exogenous input (ARX) model was used to estimate the hemodynamic impulse response function (HIRF) based on the data from simultaneous EEG-fMRI measurement. Changes in the measured BOLD signal from the right primary visual cortex and bilateral visual association cortices were consistently coupled to IEDs. The linear ARX model was applied here to confirm that a linear transform can be used to study the correlation between BOLD signal and its corresponding neural activity in this animal model of occipital epilepsy. PMID:16414283

  17. Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure.

    PubMed

    Hosseinzadeh, Mahshid; Nikseresht, Sara; Khodagholi, Fariba; Naderi, Nima; Maghsoudi, Nader

    2016-04-01

    Abnormal and sometimes severe behavioral and molecular symptoms are usually observed in epileptic humans and animals. To address this issue, we examined the behavioral and molecular aspects of seizure evoked by pilocarpine. Autophagy can promote both cell survival and death, but there are controversial reports about the neuroprotective or neurodegenerative effects of autophagy in seizure. Cannabidiol has anticonvulsant properties in some animal models when used as a pretreatment. In this study, we investigated alteration of seizure scores, autophagy pathway proteins, and antioxidant status in hippocampal cells during the chronic phase of pilocarpine-induced epilepsy after treatment with cannabidiol. Cannabidiol (100 ng, intracerebroventricular injection) delayed the chronic phase of epilepsy. Single administration of cannabidiol during the chronic phase of seizure significantly diminished seizure scores such as mouth clonus, head nodding, monolateral and bilateral forelimb clonus and increased the activity of catalase enzyme and reduced glutathione content. Such a protective effect in the behavioral scores of epileptic rats was also observed after repeated administrations of cannabidiol at the onset of the silent phase. Moreover, the amount of Atg7, conjugation of Atg5/12, Atg12, and LC3II/LC3I ratio increased significantly in epileptic rats treated with repeated injections of cannabidiol. In short, our results suggest that post-treatment of Cannabidiol could enhance the induction of autophagy pathway and antioxidant defense in the chronic phase of epilepsy, which could be considered as the protective mechanisms of cannabidiol in a temporal lobe epilepsy model. PMID:26738731

  18. Concordance of Epileptic Networks Associated with Epileptic Spikes Measured by High-Density EEG and Fast fMRI

    PubMed Central

    Jäger, Vera; Dümpelmann, Matthias; LeVan, Pierre; Ramantani, Georgia; Mader, Irina; Schulze-Bonhage, Andreas; Jacobs, Julia

    2015-01-01

    Objective The present study aims to investigate whether a newly developed fast fMRI called MREG (magnetic resonance encephalography) measures metabolic changes related to interictal epileptic discharges (IED). For this purpose BOLD changes are correlated with the IED distribution and variability. Methods Patients with focal epilepsy underwent EEG-MREG using a 64 channel cap. IED voltage maps were generated using 32 and 64 channels and compared regarding their correspondence to the BOLD response. The extents of IEDs (defined as number of channels with >50% of maximum IED negativity) were correlated with the extents of positive and negative BOLD responses. Differences in inter-spike variability were investigated between interictal epileptic discharges (IED) sets with and without concordant positive or negative BOLD responses. Results 17 patients showed 32 separate IED types. In 50% of IED types the BOLD changes could be confirmed by another independent imaging method. The IED extent significantly correlated with the positive BOLD extent (p = 0.04). In 6 patients the 64-channel EEG voltage maps better reflected the positive or negative BOLD response than the 32-channel EEG; in all others no difference was seen. Inter-spike variability was significantly lower in IED sets with than without concordant positive or negative BOLD responses (with p = 0.04). Significance Higher density EEG and fast fMRI seem to improve the value of EEG-fMRI in epilepsy. The correlation of positive BOLD and IED extent could suggest that widespread BOLD responses reflect the IED network. Inter-spike variability influences the likelihood to find IED concordant positive or negative BOLD responses, which is why single IED analysis may be promising. PMID:26496480

  19. Non-epileptic clinical diagnoses in children referred for an outpatient EEG using video monitoring.

    PubMed

    Apakama, Okwuchi; Appleton, Richard

    2006-06-01

    Simultaneous video (closed circuit television [CCTV]) and EEG recordings are important in the differentiation of epileptic and non-epileptic paroxysmal episodes and in the classification of epilepsy syndromes. An additional benefit from the observation of the child on CCTV is the possible identification of specific clinical, including genetic, conditions. This three-year prospective study of 2780 consecutive children undergoing routine EEG investigations identified 17 conditions that had not previously been diagnosed by the clinicians who had requested the EEG. PMID:16793578

  20. Immunological findings in epileptic and febrile convulsion patients before and under treatment.

    PubMed

    Tartara, A; Verri, A P; Nespoli, L; Moglia, A; Botta, M G

    1981-01-01

    Serum immunoglobulin levels of 86 epileptic patients have been evaluated in order to investigate the relationship between epilepsy, antiepileptic drugs and humoral immunity. The results confirm a high incidence of immunological disorders in the epileptic and febrile convulsion patients. These abnormalities were not related to clinical type of epilepsy nor to the therapy; the common feature seems the early onset of seizures and antiepileptic treatment. PMID:6791931

  1. Functional neurogenesis in the adult hippocampus

    NASA Astrophysics Data System (ADS)

    van Praag, Henriette; Schinder, Alejandro F.; Christie, Brian R.; Toni, Nicolas; Palmer, Theo D.; Gage, Fred H.

    2002-02-01

    There is extensive evidence indicating that new neurons are generated in the dentate gyrus of the adult mammalian hippocampus, a region of the brain that is important for learning and memory. However, it is not known whether these new neurons become functional, as the methods used to study adult neurogenesis are limited to fixed tissue. We use here a retroviral vector expressing green fluorescent protein that only labels dividing cells, and that can be visualized in live hippocampal slices. We report that newly generated cells in the adult mouse hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells. Our findings demonstrate that newly generated cells mature into functional neurons in the adult mammalian brain.

  2. mRNA Levels of ACh-Related Enzymes in the Hippocampus of THY-Tau22 Mouse: A Model of Human Tauopathy with No Signs of Motor Disturbance.

    PubMed

    García-Gómez, Beatriz E; Fernández-Gómez, Francisco J; Muñoz-Delgado, Encarnación; Buée, Luc; Blum, David; Vidal, Cecilio J

    2016-04-01

    The microtubule-associated protein Tau tends to form aggregates in neurodegenerative disorders referred to as tauopathies. The tauopathy model transgenic (Tg) THY-Tau22 (Tau22) mouse shows disturbed septo-hippocampal transmission, memory deficits and no signs of motor dysfunction. The reports showing a hippocampal downregulation of choline acetyltransferase (ChAT) in SAMP8 mice, a model of aging, and an upregulation of acetylcholinesterase (AChE) in Tg-VLW mice, a model of FTDP17 tauopathy, may lead to think that the supply of ACh to the hippocampus can be threatened as aging or Tau pathology progress. The above was tested by comparing the mRNA levels for ACh-related enzymes in hippocampi of wild-type (wt) and Tau22 mice at ages when the neuropathological signs are debuting (3-4 months), moderate (6-7 months) and extensive (>9 months). Age-matched Tau22 and wt mice hippocampi displayed similar ChAT, AChE-T, butyrylcholinesterase (BChE) and a proline-rich membrane anchor (PRiMA) mRNA levels, any change most likely arising from ACh homeostasis. The unchanged hippocampal levels of AChE-T mRNA and enzyme activity observed in Tau22 mice, expressing G272V-P301S hTau, differed from the increase in AChE-T mRNA and activity observed in Tg-VLW mice, expressing G272V-P301L-R406W hTau. The difference supports the idea that AChE upregulation may proceed or not depending on the particular Tau mutation, which would dictate Tau folding, the accessibility/affinity to kinases and phosphatases, and P-Tau aggregation with itself and protein partners, transcription factors included. PMID:26697857

  3. Diagnostic Approach to Genetic Causes of Early-Onset Epileptic Encephalopathy.

    PubMed

    Gürsoy, Semra; Erçal, Derya

    2016-03-01

    Epileptic encephalopathies are characterized by recurrent clinical seizures and prominent interictal epileptiform discharges seen during the early infantile period. Although epileptic encephalopathies are mostly associated with structural brain defects and inherited metabolic disorders, pathogenic gene mutations may also be involved in the development of epileptic encephalopathies even when no clear genetic inheritance patterns or consanguinity exist. The most common epileptic encephalopathies are Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome and Dravet syndrome, which are usually unresponsive to traditional antiepileptic medication. Many of the diagnoses describe the phenotype of these electroclinical syndromes, but not the underlying causes. To date, approximately 265 genes have been defined in epilepsy and several genes including STXBP1, ARX, SLC25A22, KCNQ2, CDKL5, SCN1A, and PCDH19 have been found to be associated with early-onset epileptic encephalopathies. In this review, we aimed to present a diagnostic approach to primary genetic causes of early-onset epileptic encephalopathies. PMID:26271793

  4. Copper sensitivity in dorsal hippocampus slices.

    PubMed

    Leiva, J; Palestini, M; Tetas, M; López, J

    2000-04-01

    The action of copper on the pyramidal neurons in CA1 of the hippocampus is little understood. Our main aim was to study the possible interaction of copper on the synaptic network in CA1 pyramidal neurons. We used Wistar rats hippocampus slices in a recording chamber. The population response ("population of spikes") collected by an extracellular micropipette under baseline conditions served as control. Copper, GABA, bicuculline and picrotoxin were delivered in different experimental conditions to the slice. One, 10 and 100 microM of copper concentration decreased significantly the amplitude and duration of the population spikes in relation to the control response. This effect did not show concentration dependency. Copper in bicuculline medium decreased significantly the duration response in relation to the control response and in relation to copper effect in a free bicuculline medium. This phenomenon emphasizes the copper action on the GABA (B) and (C) receptors. Copper in a picrotoxin medium increased significantly the excitability of the response. This new effect suggests that copper acts on non-GABA receptors, an effect that could be detected when the GABA receptors were inactivated. As a result of these findings it appears that, under our experimental conditions, copper generated transient sensitivity changes in pyramidal neurons of CA1 dorsal hippocampus. PMID:10782257

  5. Hippocampus responds to auditory change in rabbits.

    PubMed

    Ruusuvirta, T; Astikainen, P; Wikgren, J; Nokia, M

    2010-09-29

    Any change or novelty in the auditory environment is potentially important for survival. The cortex has been implicated in the detection of auditory change whereas the hippocampus has been associated with the detection of auditory novelty. Local field potentials (LFPs) were recorded from the CA1 area of the hippocampus in waking rabbits. In the oddball condition, a rare tone of one frequency (deviant) randomly replaced a repeated tone of another frequency (standard). In the equal-probability condition, the standard was replaced by a set of tones of nine different frequencies in order to remove the repetitive auditory background of the deviant (now labelled as control-deviant) while preserving its temporal probability. In the oddball condition, evoked potentials at 36-80 ms post-stimulus were found to have greater amplitude towards negative polarity for the deviant relative to the standard. No significant differences in response amplitudes were observed between the control-deviant and the standard. These findings suggest that the hippocampus plays a role in auditory change detection. PMID:20600633

  6. Interlamellar CA1 network in the hippocampus

    PubMed Central

    Yang, Sunggu; Yang, Sungchil; Moreira, Thais; Hoffman, Gloria; Carlson, Greg C.; Bender, Kevin J.; Alger, Bradley E.; Tang, Cha-Min

    2014-01-01

    To understand the cellular basis of learning and memory, the neurophysiology of the hippocampus has been largely examined in thin transverse slice preparations. However, the synaptic architecture along the longitudinal septo-temporal axis perpendicular to the transverse projections in CA1 is largely unknown, despite its potential significance for understanding the information processing carried out by the hippocampus. Here, using a battery of powerful techniques, including 3D digital holography and focal glutamate uncaging, voltage-sensitive dye, two-photon imaging, electrophysiology, and immunohistochemistry, we show that CA1 pyramidal neurons are connected to one another in an associational and well-organized fashion along the longitudinal axis of the hippocampus. Such CA1 longitudinal connections mediate reliable signal transfer among the pyramidal cells and express significant synaptic plasticity. These results illustrate a need to reconceptualize hippocampal CA1 network function to include not only processing in the transverse plane, but also operations made possible by the longitudinal network. Our data will thus provide an essential basis for future computational modeling studies on information processing operations carried out in the full 3D hippocampal network that underlies its complex cognitive functions. PMID:25139992

  7. Interlamellar CA1 network in the hippocampus.

    PubMed

    Yang, Sunggu; Yang, Sungchil; Moreira, Thais; Hoffman, Gloria; Carlson, Greg C; Bender, Kevin J; Alger, Bradley E; Tang, Cha-Min

    2014-09-01

    To understand the cellular basis of learning and memory, the neurophysiology of the hippocampus has been largely examined in thin transverse slice preparations. However, the synaptic architecture along the longitudinal septo-temporal axis perpendicular to the transverse projections in CA1 is largely unknown, despite its potential significance for understanding the information processing carried out by the hippocampus. Here, using a battery of powerful techniques, including 3D digital holography and focal glutamate uncaging, voltage-sensitive dye, two-photon imaging, electrophysiology, and immunohistochemistry, we show that CA1 pyramidal neurons are connected to one another in an associational and well-organized fashion along the longitudinal axis of the hippocampus. Such CA1 longitudinal connections mediate reliable signal transfer among the pyramidal cells and express significant synaptic plasticity. These results illustrate a need to reconceptualize hippocampal CA1 network function to include not only processing in the transverse plane, but also operations made possible by the longitudinal network. Our data will thus provide an essential basis for future computational modeling studies on information processing operations carried out in the full 3D hippocampal network that underlies its complex cognitive functions. PMID:25139992

  8. Entorhinal cortex lesions result in adenosine-sensitive high frequency oscillations in the hippocampus.

    PubMed

    Ortiz, Franco; Gutiérrez, Rafael

    2015-09-01

    Entorhinal cortex (EC) projections to the hippocampus run along the perforant path and activate the hippocampal area CA3 and the dentate gyrus (DG), which, in turn, drives CA3. Because cortical trauma damages the source of inputs to the hippocampus, we hypothesize that such an event can be reflected in immediate alterations of the hippocampal oscillatory activity. We here explore whether acute, localized disruption of EC-EC connectivity is involved in the generation or modulation of high frequency oscillations (HFOs) in the hippocampus. We conducted in vitro electrophysiological recordings in CA3 and DG of combined EC-hippocampal transversal slices prepared from intact brains and from brains with a spatially defined, transversal cut of the EC made in situ, 2h before in vitro recordings commenced. We also determined if pharmacological manipulations of the adenosine system modulated the fast oscillatory activity. EC-hippocampal slices prepared from brains, in which a transversal lesion of the EC was uni- or bilaterally conducted in situ, displayed spontaneous epileptiform events with superimposed ripples (150-250 Hz) and fast ripples (>250 Hz), whereas those obtained from non-lesioned brains did not have spontaneous HFOs. However, in the latter, high frequency stimulation applied to the perforant path produced ripple activity in area CA3. Spontaneous fast ripples were prevented by conducting the slicing procedure and incubating the slices both in a Na(+)-free medium and in a low Ca(++)-high Mg(++) medium for an hour before recording commenced, under normal Na(+) concentration. Activation of A1, but not A2, receptors produced a strong inhibition of the incidence and spectral power of fast ripples but did not change their intrinsic frequency. Our data show that the disruption of EC-to-EC connections can immediately disinhibit hippocampal CA3 area to generate HFOs on top of epileptiform events, probably constituting an irritating focus long before overt epileptic

  9. All together now: Analogies between chimera state collapses and epileptic seizures

    PubMed Central

    Andrzejak, Ralph G.; Rummel, Christian; Mormann, Florian; Schindler, Kaspar

    2016-01-01

    Conceptually and structurally simple mathematical models of coupled oscillator networks can show a rich variety of complex dynamics, providing fundamental insights into many real-world phenomena. A recent and not yet fully understood example is the collapse of coexisting synchronous and asynchronous oscillations into a globally synchronous motion found in networks of identical oscillators. Here we show that this sudden collapse is promoted by a further decrease of synchronization, rather than by critically high synchronization. This strikingly counterintuitive mechanism can be found also in nature, as we demonstrate on epileptic seizures in humans. Analyzing spatiotemporal correlation profiles derived from intracranial electroencephalographic recordings (EEG) of seizures in epilepsy patients, we found a pronounced decrease of correlation at the seizure onsets. Applying our findings in a closed-loop control scheme to models of coupled oscillators in chimera states, we succeed in both provoking and preventing outbreaks of global synchronization. Our findings not only advance the understanding of networks of coupled dynamics but can open new ways to control them, thus offering a vast range of potential new applications. PMID:26957324

  10. All together now: Analogies between chimera state collapses and epileptic seizures

    NASA Astrophysics Data System (ADS)

    Andrzejak, Ralph G.; Rummel, Christian; Mormann, Florian; Schindler, Kaspar

    2016-03-01

    Conceptually and structurally simple mathematical models of coupled oscillator networks can show a rich variety of complex dynamics, providing fundamental insights into many real-world phenomena. A recent and not yet fully understood example is the collapse of coexisting synchronous and asynchronous oscillations into a globally synchronous motion found in networks of identical oscillators. Here we show that this sudden collapse is promoted by a further decrease of synchronization, rather than by critically high synchronization. This strikingly counterintuitive mechanism can be found also in nature, as we demonstrate on epileptic seizures in humans. Analyzing spatiotemporal correlation profiles derived from intracranial electroencephalographic recordings (EEG) of seizures in epilepsy patients, we found a pronounced decrease of correlation at the seizure onsets. Applying our findings in a closed-loop control scheme to models of coupled oscillators in chimera states, we succeed in both provoking and preventing outbreaks of global synchronization. Our findings not only advance the understanding of networks of coupled dynamics but can open new ways to control them, thus offering a vast range of potential new applications.

  11. Nav1.1 Modulation by a Novel Triazole Compound Attenuates Epileptic Seizures in Rodents

    PubMed Central

    2015-01-01

    Here, we report the discovery of a novel anticonvulsant drug with a molecular organization based on the unique scaffold of rufinamide, an anti-epileptic compound used in a clinical setting to treat severe epilepsy disorders such as Lennox-Gastaut syndrome. Although accumulating evidence supports a working mechanism through voltage-gated sodium (Nav) channels, we found that a clinically relevant rufinamide concentration inhibits human (h)Nav1.1 activation, a distinct working mechanism among anticonvulsants and a feature worth exploring for treating a growing number of debilitating disorders involving hNav1.1. Subsequent structure–activity relationship experiments with related N-benzyl triazole compounds on four brain hNav channel isoforms revealed a novel drug variant that (1) shifts hNav1.1 opening to more depolarized voltages without further alterations in the gating properties of hNav1.1, hNav1.2, hNav1.3, and hNav1.6; (2) increases the threshold to action potential initiation in hippocampal neurons; and (3) greatly reduces the frequency of seizures in three animal models. Altogether, our results provide novel molecular insights into the rational development of Nav channel-targeting molecules based on the unique rufinamide scaffold, an outcome that may be exploited to design drugs for treating disorders involving particular Nav channel isoforms while limiting adverse effects. PMID:24635129

  12. Alzheimer's disease pathology in the neocortex and hippocampus of the western lowland gorilla (Gorilla gorilla gorilla).

    PubMed

    Perez, Sylvia E; Raghanti, Mary Ann; Hof, Patrick R; Kramer, Lynn; Ikonomovic, Milos D; Lacor, Pascale N; Erwin, Joseph M; Sherwood, Chet C; Mufson, Elliott J

    2013-12-15

    The two major histopathologic hallmarks of Alzheimer's disease (AD) are amyloid beta protein (Aβ) plaques and neurofibrillary tangles (NFT). Aβ pathology is a common feature in the aged nonhuman primate brain, whereas NFT are found almost exclusively in humans. Few studies have examined AD-related pathology in great apes, which are the closest phylogenetic relatives of humans. In the present study, we examined Aβ and tau-like lesions in the neocortex and hippocampus of aged male and female western lowland gorillas using immunohistochemistry and histochemistry. Analysis revealed an age-related increase in Aβ-immunoreactive plaques and vasculature in the gorilla brain. Aβ plaques were more abundant in the neocortex and hippocampus of females, whereas Aβ-positive blood vessels were more widespread in male gorillas. Plaques were also Aβ40-, Aβ42-, and Aβ oligomer-immunoreactive, but only weakly thioflavine S- or 6-CN-PiB-positive in both sexes, indicative of the less fibrillar (diffuse) nature of Aβ plaques in gorillas. Although phosphorylated neurofilament immunostaining revealed a few dystrophic neurites and neurons, choline acetyltransferase-immunoreactive fibers were not dystrophic. Neurons stained for the tau marker Alz50 were found in the neocortex and hippocampus of gorillas at all ages. Occasional Alz50-, MC1-, and AT8-immunoreactive astrocyte and oligodendrocyte coiled bodies and neuritic clusters were seen in the neocortex and hippocampus of the oldest gorillas. This study demonstrates the spontaneous presence of both Aβ plaques and tau-like lesions in the neocortex and hippocampus in old male and female western lowland gorillas, placing this species at relevance in the context of AD research. PMID:23881733

  13. Structure-function associations in hippocampus in bipolar disorder.

    PubMed

    Chepenik, Lara G; Wang, Fei; Spencer, Linda; Spann, Marisa; Kalmar, Jessica H; Womer, Fay; Kale Edmiston, E; Pittman, Brian; Blumberg, Hilary P

    2012-04-01

    Hippocampus volume decreases and verbal memory deficits have been reported in bipolar disorder (BD) as independent observations. We investigated potential associations between these deficits in subjects with BD. Hippocampus volumes were measured on magnetic resonance images of 31 subjects with BD and 32 healthy comparison (HC) subjects. The California Verbal Learning Test-Second Edition (CVLT) assessed verbal memory function in these subjects. Compared to the HC group, the BD group showed both significantly smaller hippocampus volumes and impaired performance on CVLT tests of immediate, short delay and long delay cued and free recall. Further, smaller hippocampus volume correlated with impaired performance in BD. Post hoc analyses revealed a trend towards improved memory in BD subjects taking antidepressant medications. These results support associations between morphological changes in hippocampus structure in BD and verbal memory impairment. They provide preliminary evidence pharmacotherapy may reverse hippocampus-related memory deficits. PMID:22342942

  14. Ensemble Classifier for Epileptic Seizure Detection for Imperfect EEG Data

    PubMed Central

    Mahmuddin, Massudi; Mohamed, Amr

    2015-01-01

    Brain status information is captured by physiological electroencephalogram (EEG) signals, which are extensively used to study different brain activities. This study investigates the use of a new ensemble classifier to detect an epileptic seizure from compressed and noisy EEG signals. This noise-aware signal combination (NSC) ensemble classifier combines four classification models based on their individual performance. The main objective of the proposed classifier is to enhance the classification accuracy in the presence of noisy and incomplete information while preserving a reasonable amount of complexity. The experimental results show the effectiveness of the NSC technique, which yields higher accuracies of 90% for noiseless data compared with 85%, 85.9%, and 89.5% in other experiments. The accuracy for the proposed method is 80% when SNR = 1 dB, 84% when SNR = 5 dB, and 88% when SNR = 10 dB, while the compression ratio (CR) is 85.35% for all of the datasets mentioned. PMID:25759863

  15. Self-control of epileptic seizures by nonpharmacological strategies.

    PubMed

    Kotwas, Iliana; McGonigal, Aileen; Trebuchon, Agnès; Bastien-Toniazzo, Mireille; Nagai, Yoko; Bartolomei, Fabrice; Micoulaud-Franchi, Jean-Arthur

    2016-02-01

    Despite the unpredictability of epileptic seizures, many patients report that they can anticipate seizure occurrence. Using certain alert symptoms (i.e., auras, prodromes, precipitant factors), patients can adopt behaviors to avoid injury during and after the seizure or may implement spontaneous cognitive and emotional strategies to try to control the seizure itself. From the patient's view point, potential means of enhancing seizure prediction and developing seizure control supports are seen as very important issues, especially when the epilepsy is drug-resistant. In this review, we first describe how some patients anticipate their seizures and whether this is effective in terms of seizure prediction. Secondly, we examine how these anticipatory elements might help patients to prevent or control their seizures and how the patient's neuropsychological profile, specifically parameters of perceived self-control (PSC) and locus of control (LOC), might impact these strategies and quality of life (QOL). Thirdly, we review the external supports that can help patients to better predict seizures. Finally, we look at nonpharmacological means of increasing perceived self-control and achieving potential reduction of seizure frequency (i.e., stress-based and arousal-based strategies). In the past few years, various approaches for detection and control of seizures have gained greater interest, but more research is needed to confirm a positive effect on seizure frequency as well as on QOL. PMID:26780213

  16. Coexistence of epileptic nocturnal wanderings and an arachnoid cyst.

    PubMed

    Jiménez-Genchi, Alejandro; Díaz-Galviz, John L; García-Reyna, Juan Carlos; Avila-Ordoñez, Mario U

    2007-06-15

    Episodic nocturnal wanderings (ENWs) have rarely been associated with gross abnormalities of brain structures. We describe the case of a patient with ENWs in coexistence with an arachnoid cyst (AC). The patient was a 15-year-old boy who presented with nocturnal attacks characterized by complex motor behaviors. An MRI revealed a left temporal cyst and a SPECT Tc99 scan showed left temporal hypoperfusion and bilateral frontal hyperperfusion, more evident on the right side. During an all-night polysomnographic recording with audiovisual monitoring, dystonic posture followed by sleepwalking-like behavior was documented. The sleepwalking-like behavior was preceded by a spike discharge over the left frontocentral region with contralateral projection and secondary generalization during stage 2 sleep. Treatment with levetiracetam produced a striking remission of seizures. This supports a conservative management of an AC, considering that it may be an incidental finding. In epileptic patients, an AC may not necessarily be related to the location of the seizure focus. PMID:17694730

  17. Location of Irritative Zone in Epileptic Brains of Schizencephalic Patients.

    PubMed

    Kim, Do-Hyung; Kwon, Oh-Young; Jung, Suck-Won; Jeong, Heejeong; Son, Seongnam; Kim, Soo-Kyoung; Kang, Heeyoung; Park, Ki-Jong; Choi, Nack-Cheon; Lim, ByeongHoon

    2016-07-01

    Although many schizencephaly patients suffer from epilepsy, the relationship between schizencephalic lesions and epileptic foci remains unclear. Previous studies have shown that schizencephalic lesions may be associated with, rather than contain, epileptogenic zones. Thus, the purpose of this study was to investigate the current source distribution (CSD) of epileptiform discharges in schizencephalic patients and to correlate this activity with existing structural lesions. A consecutive series of 30 schizencephalic patients who were diagnosed using brain magnetic resonance imaging (MRI) were selected retrospectively and prospectively. Of the original 30 subjects selected, 13 had epilepsy, and 6 of these patients exhibited schizencephaly, epilepsy, and interictal spikes on electroencephalograms (EEG) and were enrolled in the present study investigating the current source analysis of interictal spikes. The CSDs of the initial rising phases and the peak points of the interictal spikes were obtained using standardized low-resolution brain electromagnetic tomography (LORETA). Five patients exhibited a single focus of interictal spikes, while 1 patient showed 2 foci. Relative to the structural brain lesions, 5 patients displayed extrinsically localized CSDs, while 1 patient showed a partially intrinsically localized CSD. The present findings demonstrate that the CSDs of interictal spikes in schizencephalic patients are in general anatomically distinct from the cerebral schizencephalic lesions and that these lesions may display an extrinsic epileptogenicity. PMID:25253435

  18. Association of mitochondrial letm1 with epileptic seizures.

    PubMed

    Zhang, Xiaogang; Chen, Guojun; Lu, Yaodong; Liu, Jing; Fang, Min; Luo, Jing; Cao, Qingqing; Wang, Xuefeng

    2014-10-01

    Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1) is a mitochondrial protein that is associated with seizure attacks in Wolf-Hirschhorn syndrome. This study aimed to investigate the expression pattern of Letm1 in patients with temporal lobe epilepsy (TLE) and pilocarpine-induced rat model of epilepsy, and to determine if altered Letm1 leads to mitochondrial dysfunction and increased susceptibility to seizures. Using immunohistochemical, immunofluorescent, western blotting, and transmission electron microscopic methods, we have found that Letm1 was significantly decreased in TLE patients, and gradually decreased in experimental rats from 1 to 7 days after onset of seizures. Letm1 knock-down by a lentivirus bearing LV-Letm1-sh resulted in mitochondrial swelling and decreased expression of Letm1 target protein mitochondrially encoded cytochrome B (MT-CYB). Behavioral study revealed that inhibition of Letm1 caused early onset of the first seizure, increased seizure frequency, and duration. However, administration of Letm1 homolog nigericin failed to prevent epilepsy. These results indicate that inhibition of Letm1 and mitochondrial dysfunctions contributes to the development of epileptic seizures. Appropriate Letm1 level may be critical for maintaining normal neuronal functions. PMID:23645710

  19. The epileptic singers of belle époque Paris.

    PubMed

    Baxendale, Sallie; Marshall, Fiona

    2012-12-01

    In late 19th century Paris, people with epilepsy were treated alongside those with hysteria in the now famous Salpêtrière Hospital, where both conditions were deemed to have a neurological basis. When Jean Martin Charcot became chief physician at the Salpêtrière Hospital in 1862, he described himself 'in possession of a kind of museum of living pathology whose holdings were virtually inexhaustible'. He opened the doors of his 'living museum' and exhibited his prize specimens to all of Paris. By putting his patients on display, Charcot introduced a vogue for pathology that permeated well beyond the world of medical enquiry and into the public psyche and vernacular. Not only did Charcot's demonstrations provide the inspiration for high culture in the form of operas, plays and novels, they also provided the inspiration for the 'gommeuses epileptiques' (epileptic singers), who entertained the masses at the café concerts. This paper explores the foundations of our current medical approaches to mental illness and epilepsy, with a particular focus on the boundaries that emerged between hysteria and epilepsy in 19th century Paris. These clinical boundaries were both shaped by and reflected in the popular entertainments in the city. PMID:22613757

  20. The dilemma of treatments for epileptic patients with depression.

    PubMed

    Yang, Yang; Gao, Xia; Xu, Yao

    2015-01-01

    Depression is a state of low mood and aversion to activity. It may occur due to existence of other mental or physical diseases or from the medications for those illnesses. It is one of the leading sources of disability. Among these physical diseases, epilepsy is widely recognized as one of the main causes of depression. Patients with epilepsy are at high risk of developing depressive symptoms, and the suicide rates in patients with epilepsy have been reported to be much higher than in the general population. However, due to fears of lowering seizure threshold and adverse drug interactions between antidepressants and antiepileptic drugs, physician are reluctant to place patients with epilepsy on antidepressant medication. As a result, the question has been raised that what the best managements should be used to treat epileptic patients with depression. In this review, the currently used medications for antidepressants and antiepileptic drugs were summarized by their working targets in order to establish appropriate pharmacological management of depression and epilepsy. Despite the complex relationship between epilepsy and depression, coadministration of antidepressants and AEDs can still be done safely and effectively under the conditions of good clinical management. The ideal antidepressants for people with epilepsy should be efficacious but with few adverse effects, which will not antagonize GABAergic mechanisms or interfere with plasma anticonvulsant concentrations. PMID:25271800

  1. Do energy drinks cause epileptic seizure and ischemic stroke?

    PubMed

    Dikici, Suber; Saritas, Ayhan; Besir, Fahri Halit; Tasci, Ahmet Hakan; Kandis, Hayati

    2013-01-01

    Energy drinks are popular among young individuals and marketed to college students, athletes, and active individuals between the ages of 21 and 35 years. We report a case that had ischemic stroke and epileptic seizure after intake of energy drink with alcohol. To the best of our knowledge, the following case is the first report of ischemic stroke after intake of energy drink. A previously healthy 37-year-old man was brought to the emergency department after a witnessed tonic-clonic seizure. According to his wife's testimony, just before loss of consciousness, the patient had been drinking 3 boxes of energy drinks (Redbull, Istanbul, Turkey, 250 mL) with vodka on an empty stomach. He did not have a history of seizures, head trauma, or family history of seizures or another disease. In cranial diffusion magnetic resonance imaging, there were hyperintense signal changes in bilateral occipital area (more pronounced in the left occipital lobe), right temporal lobe, frontal lobe, and posterior parietal lobe. All tests associated with possible etiologic causes of ischemic stroke in young patients were negative. Herein, we want to attract attention to adverse effect of energy drink usage. PMID:22867827

  2. Magnetoencephalographic signatures of insular epileptic spikes based on functional connectivity.

    PubMed

    Zerouali, Younes; Pouliot, Philippe; Robert, Manon; Mohamed, Ismail; Bouthillier, Alain; Lesage, Frédéric; Nguyen, Dang K

    2016-09-01

    Failure to recognize insular cortex seizures has recently been identified as a cause of epilepsy surgeries targeting the temporal, parietal, or frontal lobe. Such failures are partly due to the fact that current noninvasive localization techniques fare poorly in recognizing insular epileptic foci. Our group recently demonstrated that magnetoencephalography (MEG) is sensitive to epileptiform spikes generated by the insula. In this study, we assessed the potential of distributed source imaging and functional connectivity analyses to distinguish insular networks underlying the generation of spikes. Nineteen patients with operculo-insular epilepsy were investigated. Each patient underwent MEG as well as T1-weighted magnetic resonance imaging (MRI) as part of their standard presurgical evaluation. Cortical sources of MEG spikes were reconstructed with the maximum entropy on the mean algorithm, and their time courses served to analyze source functional connectivity. The results indicate that the anterior and posterior subregions of the insula have specific patterns of functional connectivity mainly involving frontal and parietal regions, respectively. In addition, while their connectivity patterns are qualitatively similar during rest and during spikes, couplings within these networks are much stronger during spikes. These results show that MEG can establish functional connectivity-based signatures that could help in the diagnosis of different subtypes of insular cortex epilepsy. Hum Brain Mapp 37:3250-3261, 2016. © 2016 Wiley Periodicals, Inc. PMID:27220112

  3. Transitive inference: distinct contributions of rostrolateral prefrontal cortex and the hippocampus.

    PubMed

    Wendelken, Carter; Bunge, Silvia A

    2010-05-01

    The capacity to reason about complex information is a central characteristic of human cognition. An important component of many reasoning tasks is the need to integrate multiple mental relations. Several researchers have argued that rostrolateral prefrontal cortex (RLPFC) plays a key role in relational integration. If this hypothesis is correct, then RLPFC should play a key role in transitive inference, which requires the integration of multiple relations to reach a conclusion. Thus far, however, neuroscientific research on transitive inference has focused primarily on the hippocampus. In this fMRI study, we sought to compare the roles of RLPFC and the hippocampus on a novel transitive inference paradigm. Four relations between colored balls were presented on the screen together with a target relation. Participants were asked to decide whether the target relation was correct, given the other indicated relations between balls. RLPFC, but not the hippocampus, exhibited stronger activation on trials that required relational integration as compared with trials that involved relational encoding without integration. In contrast, the hippocampus exhibited a pattern consistent with a role in relational encoding, with stronger activation on trials requiring encoding of relational predicate-argument structure as compared with trials requiring encoding of item-item associations. Functional connectivity analyses give rise to the hypothesis that RLPFC draws on hippocampal representations of mental relations during the process of relational integration. PMID:19320546

  4. Genomic approach to selective vulnerability of the hippocampus in brain ischemia-hypoxia.

    PubMed

    Schmidt-Kastner, Rainald

    2015-11-19

    Transient global ischemia selectively damages neurons in specific brain areas. A reproducible pattern of selective vulnerability is observed in the dorsal hippocampus of rodents where ischemic damage typically affects neurons in the CA1 area while sparing neurons in CA3 and granule cells. The "neuronal factors" underlying the differential vulnerability of CA1 versus CA3 have been of great interest. This review first provides on overview of the histological pattern of ischemic-hypoxic damage, the phenomenon of delayed neuronal death, the necrosis-apoptosis discussion, and multiple molecular mechanisms studied in the hippocampus. Subsequently, genomic studies of basal gene expression in CA1 and CA3 are summarized and changes in gene expression in response to global brain ischemia are surveyed. A formal analysis is presented for the overlap between genes expressed under basal conditions in the hippocampus and genes responding to ischemia-hypoxia in general. A possible role of the elusive vascular factors in selective vulnerability is reviewed, and a gene set for angiogenesis is then shown to be enriched in the CA3 gene set. A survey of selective vulnerability in the human hippocampus in relation to genomic studies in ischemia-hypoxia is presented, and neurodegeneration genes with high expression in CA1 are highlighted (e.g. WFS1). It is concluded that neuronal factors dominate the selective vulnerability of CA1 but that vascular factors also deserve more systematic studies. PMID:26383255

  5. The effects of 30 mT electromagnetic fields on hippocampus cells of rats

    PubMed Central

    Teimori, Farzaneh; Khaki, Amir A.; Rajabzadeh, Asghar; Roshangar, Leila

    2016-01-01

    Background: Despite the use of electromagnetic waves in the treatment of some acute and chronic diseases, application of these waves in everyday life has created several problems for humans, especially the nerve system. In this study, the effects of 30mT electromagnetic fields (EMFs) on the hippocampus is investigated. Methods: Twenty-four 5-month Wistar rats weighing 150–200 g were divided into two groups. The experimental group rats were under the influence of an EMF at an intensity of 3 mT for approximately 4 hours a day (from 8 AM to 12 PM) during 10 weeks. After the hippocampus was removed, thin slides were prepared for transmission electron microscope (TEM) to study the ultrastructural tissue. Cell death detection POD kits were used to determine the apoptosis rate. Results: The results of the TEM showed that, in the hippocampus of the experimental group, in comparison to the control group, there was a substantial shift; even intracellular organelles such as the mitochondria were morphologically abnormal and uncertain. The number of apoptotic cells in the exposed group compared to the control group showed significant changes. Conclusions: Similar to numerous studies that have reported the effects of EMFs on nerves system, it was also confirmed in this lecture. Hence, the hippocampus which is important in regulating emotions, behavior, motivation, and memory functions, may be impaired by the negative impacts of EMFs. PMID:27453795

  6. Region specific neuron loss in the aged canine hippocampus is reduced by enrichment.

    PubMed

    Siwak-Tapp, Christina T; Head, Elizabeth; Muggenburg, Bruce A; Milgram, Norton W; Cotman, Carl W

    2008-01-01

    Neuron loss within the hippocampus and entorhinal cortex occurs as a function of age in humans. We first tested the hypothesis that neuron loss occurs in the aged dog. The total unilateral number of neurons in the canine entorhinal cortex and subdivisions of the hippocampus from the left hemisphere were estimated using the optical fractionator. The brains from 5 old (13.0-15.0 years old) and 5 young (3.4-4.5 years old) beagle dogs were analyzed. The hilus of the hippocampus showed a significant loss of neurons (approximately 30%) in the aged dog brain compared to young. Differences were not detected in the remaining hippocampal subfields and entorhinal cortex. We further tested the hypothesis that an antioxidant fortified food or behavioral enrichment would reduce the age-related loss of hilar neurons. Behaviorally enriched aged dogs had more neurons in the hilus (approximately 18%) compared to aged controls. These results suggest that the aged canine hippocampus in the left hemisphere shows selective neuron loss and that behavioral enrichment may reduce this loss. PMID:17092609

  7. The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects

    PubMed Central

    Sadeghi, Akram; Hami, Javad; Razavi, Shahnaz; Esfandiary, Ebrahim; Hejazi, Zahra

    2016-01-01

    Background: Diabetes mellitus is associated with cognitive deficits in humans and animals. These deficits are paralleled by neurophysiological and structural changes in brain. In diabetic animals, impairments of spatial learning, memory, and cognition occur in association with distinct changes in hippocampus, a key brain area for many forms of learning and memory and are particularly sensitive to changes in glucose homeostasis. However, the multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood. Apoptosis plays a crucial role in diabetes-induce neuronal loss in hippocampus. Methods: The effects of diabetes on hippocampus and cognitive/behavioral dysfunctions in experimental models of diabetes are reviewed, with a focus on the negative impact on increased neuronal apoptosis and related cellular and molecular mechanisms. Results: Of all articles that were assessed, most of the experimental studies clearly showed that diabetes causes neuronal apoptosis in hippocampus through multiple mechanisms, including oxidative stress, inhibition of caspases, disturbance in expression of apoptosis regulator genes, as well as deficits in mitochondrial function. The balance between pro-apoptotic and anti-apoptotic signaling may determine the neuronal apoptotic outcome in vitro and in vivo models of experimental diabetes. Conclusions: Dissecting out the mechanisms responsible for diabetes-related changes in the hippocampal cell apoptosis helps improve treatment of impaired cognitive and memory functions in diabetic individuals. PMID:27076895

  8. Optogenetic fMRI in the mouse hippocampus: Hemodynamic response to brief glutamatergic stimuli.

    PubMed

    Lebhardt, Philipp; Hohenberg, Christian Clemm von; Weber-Fahr, Wolfgang; Kelsch, Wolfgang; Sartorius, Alexander

    2016-03-01

    The combination of optogenetics with functional magnetic resonance imaging is a promising tool to study the causal relationship between specific neuronal populations and global brain activity. We employed this technique to study the brain response to recruitment of glutamatergic neurons in the mouse hippocampus. The light-sensitive protein channelrhodopsin-2 was expressed in α-CamKII-positive glutamatergic neurons in the left hippocampus (N = 10). Functional magnetic resonance imaging was performed during local laser stimulation, with stimulus duration of 1 second. The hemodynamic response to these stimuli was analyzed on a whole-brain level. In a secondary analysis, we examined the impact of the stimulation locus on the dorso-ventral axis within the hippocampal formation. The hemodynamic response in the mouse hippocampus had an earlier peak and a shorter duration compared to those observed in humans. Photostimulation was associated with significantly increased blood oxygen level-dependent signal in group statistics: bilaterally in the hippocampus, frontal lobe and septum, ipsilaterally in the nucleus accumbens and contralaterally in the striatum. More dorsal position of the laser fiber was associated with a stronger activation in projection regions (insular cortex and striatum). The characterization of brain-region-specific hemodynamic response functions may enable more precise interpretation of future functional magnetic resonance imaging experiments. PMID:26661158

  9. Segmentation of Infant Hippocampus Using Common Feature Representations Learned for Multimodal Longitudinal Data

    PubMed Central

    Guo, Yanrong; Wu, Guorong; Yap, Pew-Thian; Jewells, Valerie; Lin, Weili

    2016-01-01

    Aberrant development of the human brain during the first year after birth is known to cause critical implications in later stages of life. In particular, neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD), have been linked with abnormal early development of the hippocampus. Despite its known importance, studying the hippocampus in infant subjects is very challenging due to the significantly smaller brain size, dynamically varying image contrast, and large across-subject variation. In this paper, we present a novel method for effective hippocampus segmentation by using a multi-atlas approach that integrates the complementary multimodal information from longitudinal T1 and T2 MR images. In particular, considering the highly heterogeneous nature of the longitudinal data, we propose to learn their common feature representations by using hierarchical multi-set kernel canonical correlation analysis (CCA). Specifically, we will learn (1) within-time-point common features by projecting different modality features of each time point to its own modality-free common space, and (2) across-time-point common features by mapping all time-point-specific common features to a global common space for all time points. These final features are then employed in patch matching across different modalities and time points for hippocampus segmentation, via label propagation and fusion. Experimental results demonstrate the improved performance of our method over the state-of-the-art methods. PMID:27019875

  10. rhEPO affects apoptosis in hippocampus of aging rats by upregulating SIRT1

    PubMed Central

    Wu, Haiqin; Wang, Huqing; Zhang, Wenting; Wei, Xuanhui; Zhao, Jiaxin; Yan, Pu; Liu, Chao

    2015-01-01

    The aim of this study was to elucidate the signaling pathway involved in the anti-aging effect of erythropoietin (EPO) and to clarify whether recombinant human EPO (rhEPO) affects apoptosis in the aging rat hippocampus by upregulating Sirtuin 1 (SIRT1). In this study, a rat model of aging was established using D-galactose. Behavioral changes were monitored by the Morris water maze test. Using immunohistochemistry, we studied the expression of SIRT1, B-cell lymphoma/leukemia-2 gene (Bcl-2), and Bcl-2 associated X protein (Bax) expression, and apoptotic cells in the hippocampus of a rat model of aging in which rhEPO was intraperitoneally injected. The escape latency in rats from the EPO group shortened significantly; however, the number of platform passes increased significantly from that in the D-gal group (P < 0.05). Compared to the D-gal group, in the EPO group, the number of SIRT1 and Bcl-2-positive cells increased (P < 0.05), but the number of Bax-positive cells and apoptotic cells decreased in the hippocampus of aging rats (P < 0.05). These results suggest that rhEPO regulates apoptosis-related genes and affects apoptosis in the hippocampus of aging rats by upregulating SIRT. This may be one of the important pathways underlying the anti-aging property of EPO. PMID:26261574

  11. Coordinating different representations in the hippocampus.

    PubMed

    Kelemen, Eduard; Fenton, André A

    2016-03-01

    The processes that organize different thoughts and memories, allowing the separation of currently relevant and irrelevant information, are collectively known as cognitive control. The neuronal mechanisms of these processes can be investigated by place cell ensemble recordings during behaviors and environmental manipulations that present cognitive control challenges to selectively represent one of multiple possible alternative estimates of location. We review place cell studies that investigate responses to manipulations that dissociate the environment into two or more spatial frames of locations, often times to test notions of pattern separation. Manipulations, such as continuously rotating the recording chamber reveal that the ensemble discharge in hippocampus self-organizes into multiple, transiently-organized representations of space, each defined by the subset of coactive cells. Ensemble discharge in the hippocampus alternates between separate representations of frame-specific positions on timescales from 25ms to several seconds. The dynamic, functional grouping of discharge into transiently co-active subsets of cells is predicted by the animal's changing behavioral needs. In addition to identifying neural correlates of cognitive control in hippocampus, these observations demonstrate that the separation of neuronal activity into distinctive representations depends on ongoing cognitive demands and that what can appear as noise, deviations from receptive field tuning, can substantially be the result of these internal knowledge-guided fluctuations. These findings inspire a new perspective that should be taken into account when investigating pattern separation - a perspective that emphasizes changes in hippocampal neural discharge that are happening on a short timescale and does not assume that patterns of neural discharge are steady and stationary across the several minutes of the recordings. PMID:26748023

  12. LTP enhances synaptogenesis in the developing hippocampus.

    PubMed

    Watson, Deborah J; Ostroff, Linnaea; Cao, Guan; Parker, Patrick H; Smith, Heather; Harris, Kristen M

    2016-05-01

    In adult hippocampus, long-term potentiation (LTP) produces synapse enlargement while preventing the formation of new small dendritic spines. Here, we tested how LTP affects structural synaptic plasticity in hippocampal area CA1 of Long-Evans rats at postnatal day 15 (P15). P15 is an age of robust synaptogenesis when less than 35% of dendritic spines have formed. We hypothesized that LTP might therefore have a different effect on synapse structure than in adults. Theta-burst stimulation (TBS) was used to induce LTP at one site and control stimulation was delivered at an independent site, both within s. radiatum of the same hippocampal slice. Slices were rapidly fixed at 5, 30, and 120 min after TBS, and processed for analysis by three-dimensional reconstruction from serial section electron microscopy (3DEM). All findings were compared to hippocampus that was perfusion-fixed (PF) in vivo at P15. Excitatory and inhibitory synapses on dendritic spines and shafts were distinguished from synaptic precursors, including filopodia and surface specializations. The potentiated response plateaued between 5 and 30 min and remained potentiated prior to fixation. TBS resulted in more small spines relative to PF by 30 min. This TBS-related spine increase lasted 120 min, hence, there were substantially more small spines with LTP than in the control or PF conditions. In contrast, control test pulses resulted in spine loss relative to PF by 120 min, but not earlier. The findings provide accurate new measurements of spine and synapse densities and sizes. The added or lost spines had small synapses, took time to form or disappear, and did not result in elevated potentiation or depression at 120 min. Thus, at P15 the spines formed following TBS, or lost with control stimulation, appear to be functionally silent. With TBS, existing synapses were awakened and then new spines formed as potential substrates for subsequent plasticity. © 2015 The Authors Hippocampus Published by Wiley

  13. [Site and propagation of focal epileptic activity: multichannel MEG/EEG analysis].

    PubMed

    Stefan, H; Abraham-Fuchs, K; Schüler, P; Schneider, S; Neubauer, P U; Huk, H J; Neundörfer, B

    1991-12-01

    Electrophysiological examinations provide the basis for a deeper pathophysiological understanding of focal epileptic activity. In addition to electroencephalography, magnetoencephalography from field measurements is now available for biomagnetic diagnosis. As magnetoencephalography (MEG) is basically better suited for the localization of focal epileptic activity than EEG, an increase in MEG measurements has taken place over the last years. In this study we discuss magnetic source localization which was combined with anatomical 3-D-MR-images and compared with the results of EEG-registration carried out simultaneously and with other investigative procedures of presurgical diagnosis. The results of investigation show that simultaneous magnetic field measurements over one hemisphere of the skull allow localization of sources both in the temporal lobe and in deeper areas of the brain. Furthermore, propagation of epileptic activity can be registered not only in neighbouring areas of the epileptogenic source but also in regions localized deeper in the temporal lobe. This opens new possibilities for presurgical evaluation as well as an understanding of partial and generalized epilepsies. The results of investigation show primary focal epileptic activity neocortex laterally or surrounding a mesio-temporal lesion in all investigated patients with partial (temporal, frontal) and secondary generalized epilepsies. Furthermore, a pattern of propagation of focal epileptic activity which is directed from neocortical-lateral to mediobasal-limbic brain structures is found in most of these patients. PMID:1795752

  14. Perceived parental rearing behaviour and psychopathology in epileptic patients: a controlled study.

    PubMed

    Maj, M; Del Vecchio, M; Tata, M R; Guizzaro, A; Bravaccio, F; Kemali, D

    1987-01-01

    Memories of parental rearing behaviour were assessed by the EMBU in 61 epileptics and 151 healthy controls. The occurrence of the first crisis during the childhood was an inclusion criterion for patients. Epileptics, as compared with controls, rated their fathers and mothers as less stimulating, their fathers as less performance oriented and affectionate, and their mothers as more tolerant. Moreover, the score on the subscale 'favouring subject' for both fathers and mothers was higher in epileptics. As patients with and without interictal psychopathological features were compared, the scores on the subscales 'overprotective' and 'favouring subject' for mothers and 'abusive' and 'depriving' for fathers were higher in the former subgroup, whereas that on the subscale 'performance oriented' for fathers was higher in the latter. No significant difference was observed among patients suffering from the various subtypes of epilepsy. These results are consistent with the idea that parents of epileptics tend to encourage passivity in their children, have low expectations as regards their ability to operate effectively, and treat them in a more indulgent way because of their disability. Furthermore, they are in line with the reported association between maternal overprotectiveness and problem behaviour in epileptics. PMID:3130645

  15. Epileptic seizures induce structural and functional alterations on brain tissue membranes.

    PubMed

    Turker, Sevgi; Severcan, Mete; Ilbay, Gul; Severcan, Feride

    2014-12-01

    Epilepsy is characterized by disruption of balance between cerebral excitation and inhibition, leading to recurrent and unprovoked convulsions. Studies are still underway to understand mechanisms lying epileptic seizures with the aim of improving treatment strategies. In this context, the research on brain tissue membranes gains importance for generation of epileptic activities. In order to provide additional information for this field, we have investigated the effects of pentylenetetrazol-induced and audiogenetically susceptible epileptic seizures on structure, content and function of rat brain membrane components using Fourier transform infrared (FT-IR) spectroscopy. The findings have shown that both two types of epileptic seizures stimulate the variations in the molecular organization of membrane lipids, which have potential to influence the structures in connection with functions of membrane proteins. Moreover, less fluid lipid structure and a decline in content of lipids obtained from the ratio of CH3 asym/lipid, CH2 asym/lipid, CO/lipid, and olefinicCH/lipid and the areas of the PO2 symmetric and asymmetric modes were observed. Moreover, based on IR data the changes in the conformation of proteins were predicted by neural network (NN) analysis, and displayed as an increase in random coil despite a decrease in beta sheet. Depending on spectral parameters, we have successfully differentiated treated samples from the control by principal component analysis (PCA) and cluster analysis. In summary, FT-IR spectroscopy may offer promising attempt to identify compositional, structural and functional alterations in brain tissue membranes resulting from epileptic activities. PMID:25194682

  16. Guanosine may increase absence epileptic activity by means of A2A adenosine receptors in Wistar Albino Glaxo Rijswijk rats.

    PubMed

    Lakatos, Renáta Krisztina; Dobolyi, Árpád; Todorov, Mihail Ivilinov; Kékesi, Katalin A; Juhász, Gábor; Aleksza, Magdolna; Kovács, Zsolt

    2016-06-01

    The non-adenosine nucleoside guanosine (Guo) was demonstrated to decrease quinolinic acid(QA)-induced seizures, spontaneously emerged absence epileptic seizures and lipopolysaccharide(LPS)-evoked induction of absence epileptic seizures suggesting its antiepileptic potential. It was also described previously that intraperitoneal (i.p.) injection of 20 and 50mg/kg Guo decreased the number of spike-wave discharges (SWDs) in a well investigated model of human absence epilepsy, the Wistar Albino Glaxo Rijswijk (WAG/Rij) rats during 4th (20mg/kg Guo) and 3rd as well as 4th (50mg/kg Guo) measuring hours. Guanosine can potentially decrease SWD number by means of its putative receptors but absence epileptic activity changing effects of Guo by means of increased extracellular adenosine (Ado) cannot be excluded. An increase in the dose of i.p. injected Guo is limited by its low solubility in saline, therefore, we addressed in the present study whether higher doses of Guo, diluted in sodium hydroxide (NaOH) solution, have more potent antiepileptic effect in WAG/Rij rats. We confirmed that i.p. 50mg/kg Guo decreased but, surprisingly, i.p. 100mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5mg/kg) or a selective Ado A2A receptor (A2AR) antagonist SCH 58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) (1mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10mg/kg) with 100mg/kg Guo decreased the SWD number compared to i.p. 100mg/kg Guo alone. The results suggest that i.p. 100mg/kg Guo can increase SWD number by means of the adenosinergic system. PMID:27154620

  17. Ulinastatin inhibits cerebral ischemia-induced apoptosis in the hippocampus of gerbils.

    PubMed

    Cho, Young-Sam; Shin, Mal-Soon; Ko, Il-Gyu; Kim, Sung-Eun; Kim, Chang-Ju; Sung, Yun-Hee; Yoon, Hye-Sun; Lee, Bong-Jae

    2015-08-01

    Ulinastatin is a urinary trypsin inhibitor, originally extracted and purified from human urine. Ulinastatin has cytoprotective effects against ischemic injury in several organs. In the present study, the neuroprotective effects of ulinastatin following ischemic cerebral injury in the hippocampus of gerbils was investigated. To induce transient global ischemia in gerbils, the common carotid arteries were occluded using aneurysm clips for 5 min, and the clips were then removed. Ulinastatin was subcutaneously injected into the gerbils once a day for 7 days at doses of 50,000 or 100,000 U/kg. The gerbils were confronted with a step-down avoidance task, following which tissue samples from the gerbils were examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, western blot analysis for B-cell lymphoma (Bcl-2) and Bcl-2-associated X protein (Bax), immunohistochemistry for caspase-3 and immunofluorescence for 5-bromo-2'-deoxyuridine. The numbers of TUNEL-positive and caspase-3-positive cells in the hippocampal CA1 region increased following cerebral ischemia. The expression of Bax in the hippocampus increased, while the expression of Bcl-2 in the hippocampus decreased following cerebral ischemia. These results confirmed that apoptosis in the hippocampus was enhanced following cerebral ischemia in gerbils. The levels of cell proliferation in the hippocampal dentate gyrus were also enhanced by ischemia, which is possibly an adaptive mechanism to compensate for excessive levels of apoptosis. Ulinastatin treatment inhibited ischemia-induced apoptosis by suppressing apoptosis-associated molecules, and thus ameliorated ischemia-induced short-term memory impairment. The cell proliferation in the hippocampus was also suppressed following ulinastatin treatment. These results suggested the use of ulinastatin as a therapeutic agent for patients with cerebral stroke. PMID:25891426

  18. Medical management of epileptic seizures: challenges and solutions

    PubMed Central

    Sarma, Anand K; Khandker, Nabil; Kurczewski, Lisa; Brophy, Gretchen M

    2016-01-01

    Epilepsy is one of the most common neurologic illnesses. This condition afflicts 2.9 million adults and children in the US, leading to an economic impact amounting to $15.5 billion. Despite the significant burden epilepsy places on the population, it is not very well understood. As this understanding continues to evolve, it is important for clinicians to stay up to date with the latest advances to provide the best care for patients. In the last 20 years, the US Food and Drug Administration has approved 15 new antiepileptic drugs (AEDs), with many more currently in development. Other advances have been achieved in terms of diagnostic modalities like electroencephalography technology, treatment devices like vagal nerve and deep-brain stimulators, novel alternate routes of drug administration, and improvement in surgical techniques. Specific patient populations, such as the pregnant, elderly, those with HIV/AIDS, and those with psychiatric illness, present their own unique challenges, with AED side effects, drug interactions, and medical–psychiatric comorbidities adding to the conundrum. The purpose of this article is to review the latest literature guiding the management of acute epileptic seizures, focusing on the current challenges across different practice settings, and it discusses studies in various patient populations, including the pregnant, geriatric, those with HIV/AIDS, comatose, psychiatric, and “pseudoseizure” patients, and offers possible evidence-based solutions or the expert opinion of the authors. Also included is information on newer AEDs, routes of administration, and significant AED-related drug-interaction tables. This review has tried to address only some of these issues that any practitioner who deals with the acute management of seizures may encounter. The document also highlights the numerous avenues for new research that would help practitioners optimize epilepsy management. PMID:26966367

  19. Mozart's music in children with drug-refractory epileptic encephalopathies.

    PubMed

    Coppola, Giangennaro; Toro, Annacarmela; Operto, Francesca Felicia; Ferrarioli, Giuseppe; Pisano, Simone; Viggiano, Andrea; Verrotti, Alberto

    2015-09-01

    Mozart's sonata for two pianos in D major, K448, has been shown to decrease interictal EEG discharges and recurrence of clinical seizures in both adults and young patients. In this prospective, open-label study, we evaluated the effect of listening to a set of Mozart's compositions, according to the Tomatis method, on sleep quality and behavioral disorders, including auto-/hetero-aggression, irritability, and hyperactivity, in a group of children and adolescents with drug-resistant epilepsy. The study group was composed of 11 outpatients (7 males and 4 females), between 1.5years and 21years of age (mean age: 11.9years), all suffering from drug-resistant epileptic encephalopathy (n=11). All of them had a severe/profound intellectual disability associated with cerebral palsy. During the study period, each patient had to listen to a set of Mozart's compositions 2h per day for fifteen days for a total of 30h, which could be distributed over the day depending on the habits and compliance of each patient. The music was filtered by a device preferably delivering higher sound frequencies (>3000Hz) according to the Tomatis principles. The antiepileptic drug therapy remained unchanged throughout the study period. During the 15-day music therapy, 2 out of 11 patients had a reduction of 50-75% in seizure recurrence, and 3 out of 12 patients had a reduction of 75-89%. Overall, 5 (45.4%) out of 11 patients had a ≥50% reduction in the total number of seizures, while the percentage decrease of the total seizure number (11/11) compared with baseline was -51.5% during the 15-day music therapy and -20.7% in the two weeks after the end of treatment. All responders also had an improvement in nighttime sleep and daytime behavior. PMID:26093514

  20. Factors influencing serum concentration of zonisamide in epileptic patients.

    PubMed

    Kimura, M; Tanaka, N; Kimura, Y; Miyake, K; Kitaura, T; Fukuchi, H; Harada, Y

    1992-01-01

    The relationship between daily dose and serum concentration of zonisamide (ZNS) and the effects of patient age on the serum level/dose (L/D) ratio for ZNS were studied in epileptic patients (mean age +/- S.D. = 10.6 +/- 6.2 years) who chronically received ZNS. The influence of phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ) and valproic acid (VPA) on the serum protein binding of ZNS in vitro and the correlation between total and unbound serum levels of ZNS in patients were also examined. Significant correlations were obtained between daily dose per body weight or per body surface area and serum level of ZNS. The correlation coefficient of the latter was higher than that of the former. There was no effect of age on the L/D ratio on the basis of body surface area, whereas that on the basis of body weight increased significantly with age. No significant increase in the free fraction of ZNS was observed in the presence of PHT, PB and CBZ except VPA in vitro. There were significant correlations between total and unbound serum levels of ZNS in the two patient groups coadministered with and without VPA. Although the free fraction of ZNS in the former was significantly higher than that of the latter, the increase was small. These results suggest that dosage regimens on the basis of body surface area would be more accurate than those on a body weight basis and that there is little effect of other antiepileptics on the serum protein binding of ZNS. PMID:1576673

  1. Medical management of epileptic seizures: challenges and solutions.

    PubMed

    Sarma, Anand K; Khandker, Nabil; Kurczewski, Lisa; Brophy, Gretchen M

    2016-01-01

    Epilepsy is one of the most common neurologic illnesses. This condition afflicts 2.9 million adults and children in the US, leading to an economic impact amounting to $15.5 billion. Despite the significant burden epilepsy places on the population, it is not very well understood. As this understanding continues to evolve, it is important for clinicians to stay up to date with the latest advances to provide the best care for patients. In the last 20 years, the US Food and Drug Administration has approved 15 new antiepileptic drugs (AEDs), with many more currently in development. Other advances have been achieved in terms of diagnostic modalities like electroencephalography technology, treatment devices like vagal nerve and deep-brain stimulators, novel alternate routes of drug administration, and improvement in surgical techniques. Specific patient populations, such as the pregnant, elderly, those with HIV/AIDS, and those with psychiatric illness, present their own unique challenges, with AED side effects, drug interactions, and medical-psychiatric comorbidities adding to the conundrum. The purpose of this article is to review the latest literature guiding the management of acute epileptic seizures, focusing on the current challenges across different practice settings, and it discusses studies in various patient populations, including the pregnant, geriatric, those with HIV/AIDS, comatose, psychiatric, and "pseudoseizure" patients, and offers possible evidence-based solutions or the expert opinion of the authors. Also included is information on newer AEDs, routes of administration, and significant AED-related drug-interaction tables. This review has tried to address only some of these issues that any practitioner who deals with the acute management of seizures may encounter. The document also highlights the numerous avenues for new research that would help practitioners optimize epilepsy management. PMID:26966367

  2. Modern technology calls for a modern approach to classification of epileptic seizures and the epilepsies.

    PubMed

    Lüders, Hans O; Amina, Shahram; Baumgartner, Christopher; Benbadis, Selim; Bermeo-Ovalle, Adriana; Devereaux, Michael; Diehl, Beate; Edwards, Jonathan; Baca-Vaca, Guadalupe Fernandez; Hamer, Hajo; Ikeda, Akio; Kaiboriboon, Kitti; Kellinghaus, Christoph; Koubeissi, Mohamad; Lardizabal, David; Lhatoo, Samden; Lüders, Jürgen; Mani, Jayanti; Mayor, Luis Carlos; Miller, Jonathan; Noachtar, Soheyl; Pestana, Elia; Rosenow, Felix; Sakamoto, Americo; Shahid, Asim; Steinhoff, Bernhard J; Syed, Tanvir; Tanner, Adriana; Tsuji, Sadatoshi

    2012-03-01

    In the last 10-15 years the ILAE Commission on Classification and Terminology has been presenting proposals to modernize the current ILAE Classification of Epileptic Seizures and Epilepsies. These proposals were discussed extensively in a series of articles published recently in Epilepsia and Epilepsy Currents. There is almost universal consensus that the availability of new diagnostic techniques as also of a modern understanding of epilepsy calls for a complete revision of the Classification of Epileptic Seizures and Epilepsies. Unfortunately, however, the Commission is still not prepared to take a bold step ahead and completely revisit our approach to classification of epileptic seizures and epilepsies. In this manuscript we critically analyze the current proposals of the Commission and make suggestions for a classification system that reflects modern diagnostic techniques and our current understanding of epilepsy. PMID:22332669

  3. Management of a high risk epileptic patient under conscious sedation: A multidisciplinary approach

    PubMed Central

    Chellathurai, Burnice Nalina Kumari; Thiagarajan, Ramakrishnan; Jayakumaran, SelvaKumar; Devadoss, Pradeep; Elavazhagan

    2016-01-01

    Epilepsy, characterized by the risk of recurrent seizures, is a chronic disease that afflicts about 5% of the world's population. The main dental problems associated with epileptic patients include gingival hyperplasia, minor oral injuries, tooth trauma, and prosthodontic problems, which require the dental treatment. Stress and fear are the most common triggering factors for the epilepsy in dental chair. Therefore, a more appropriate method of treating such epileptic patients may be warranted. Conscious sedation is a technique of providing good anesthesia and analgesia to patients, the main advantage of which is the patient's rapid return to presentation levels. Midazolam used as a sedative agent has anticonvulsant properties. This case report highlights a case requiring multiple dental procedures carried out in a high risk epileptic patient under conscious sedation. PMID:27041847

  4. The Lombrosian prejudice in medicine. The case of epilepsy. Epileptic psychosis. Epilepsy and aggressiveness.

    PubMed

    Granieri, Enrico; Fazio, Patrik

    2012-02-01

    In the nineteenth century, epilepsy became subject of experimental research. Lombroso established a relationship between epilepsy and criminality believing in the existence of epileptoid traits and atavism. He tried to demonstrate the common origin of epilepsy, criminality, and genius; factors deteriorating the CNS would act upon centers, which control behavior and ethics. This impairment would cause a lack of control on the lower nervous centers, reducing restraints of instincts and criminal behavior. He described developmental frontal cortex lesions in epileptic patients (today Taylor's dysplasia) and these observations supported the erroneous conviction of a relationship between criminality and epilepsy. Neurological, behavioral, and criminological sciences analyzed Lombroso's doctrine, whereas it was controversial that epileptic patients should be prone to violent actions and aggressive behavior. Today, there is an international panel of experts on epilepsy, which suggests five relevant criteria to determine if a crime committed with aggressiveness could result from epileptic seizures. PMID:21538126

  5. Epileptic activity is a surrogate for an underlying etiology and stopping the activity has a limited impact on developmental outcome.

    PubMed

    Korff, Christian M; Brunklaus, Andreas; Zuberi, Sameer M

    2015-10-01

    The concept of epileptic encephalopathy is important in clinical practice, but its relevance to an individual must be assessed in the appropriate context. Except in rare situations, epileptic activity is a surrogate for an underlying etiology, and stopping the activity has a limited impact on developmental outcome. Labeling a group of epilepsies as "the epileptic encephalopathies," risks minimizing the impact of epileptic activity on cognition and behavior more widely in epilepsy. Similarly, describing the encephalopathy associated with many infantile onset epilepsies as "epileptic" may be misleading. Finally, concentrating on the epileptic activity alone and not considering the wider consequences of the underlying etiology on cognitive and behavioral development, may focus research efforts and the search for improved therapies on too narrow a target. Therefore, epileptic encephalopathies should not be considered as a specific group of epilepsies but, rather, the concept of epileptic encephalopathy should be applicable to all types of epilepsies and epilepsy syndromes, whenever it is relevant in the clinical course of a particular individual, at any age. PMID:26293471

  6. Effect of hydroalcoholic extract of ginger on the liver of epileptic female rats treated with lamotrigine

    PubMed Central

    Poorrostami, Ameneh; Farokhi, Farah; Heidari, Reza

    2014-01-01

    Objective: Lamotrigine is an antiepileptic drug, widely used in the treatment of epilepsy; long-term use of this drug can cause hepatotoxicity. Zingiber officinale Roscoe (ginger) possesses antioxidant properties. In present research, the effect ofhydroalcoholic extract of ginger (HEG) on the liver of lamotrigine-treated epileptic rats was investigated Material and Methods: Forty-eight female Wistar rats were selected and allocated to 8 groups of 6 each. Group 1: Negative controls were treated with normal saline. Group 2: Positive controls were treated with lamotrigine (LTG) (10 mg/kg) daily by gavages for 4 consecutive weeks. Epilepsy was induced in treatment groups by i.p. injection of pentylenetetrazol (PTZ) (40 mg/kg). Group 3: Epileptic group received normal saline (10 ml/kg). Group 4: Epileptic group was treated with LTG (10 mg/kg). Groups 5 and 6: Epileptic groups received HEG (50 and 100 mg/kg). Groups 7 and 8: Epileptic groups received LTG and HEG (50 and 100 mg/kg). At the end of 28 days, blood samples were drawn and their livers were processed for light microscopy. Results: The mean values of TG, CHOL, AST, and ALT activity significantly rose (p<0.01) in groups 2, 3, and 4, while in rats treated with HEG (groups 5, 6, 7, and 8), the levels of liver enzymes significantly decreased (p<0.05) compared with epileptic group treated with lamotrigine (group 4). Histopathological changes of liver samples were comparable with respective control. Conclusion: These results suggest that hydroalcoholic extract of ginger improves liver function in lamotrigine-induced hepatotoxicity. PMID:25068142

  7. De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies

    PubMed Central

    Appenzeller, Silke; Balling, Rudi; Barisic, Nina; Baulac, Stéphanie; Caglayan, Hande; Craiu, Dana; De Jonghe, Peter; Depienne, Christel; Dimova, Petia; Djémié, Tania; Gormley, Padhraig; Guerrini, Renzo; Helbig, Ingo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jähn, Johanna; Klein, Karl Martin; Koeleman, Bobby; Komarek, Vladimir; Krause, Roland; Kuhlenbäumer, Gregor; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes R.; Lerche, Holger; Linnankivi, Tarja; Marini, Carla; May, Patrick; Møller, Rikke S.; Muhle, Hiltrud; Pal, Deb; Palotie, Aarno; Pendziwiat, Manuela; Robbiano, Angela; Roelens, Filip; Rosenow, Felix; Selmer, Kaja; Serratosa, Jose M.; Sisodiya, Sanjay; Stephani, Ulrich; Sterbova, Katalin; Striano, Pasquale; Suls, Arvid; Talvik, Tiina; von Spiczak, Sarah; Weber, Yvonne; Weckhuysen, Sarah; Zara, Federico; Abou-Khalil, Bassel; Alldredge, Brian K.; Andermann, Eva; Andermann, Frederick; Amron, Dina; Bautista, Jocelyn F.; Berkovic, Samuel F.; Bluvstein, Judith; Boro, Alex; Cascino, Gregory; Consalvo, Damian; Crumrine, Patricia; Devinsky, Orrin; Dlugos, Dennis; Epstein, Michael P.; Fiol, Miguel; Fountain, Nathan B.; French, Jacqueline; Friedman, Daniel; Geller, Eric B.; Glauser, Tracy; Glynn, Simon; Haas, Kevin; Haut, Sheryl R.; Hayward, Jean; Helmers, Sandra L.; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi E.; Knowlton, Robert C.; Kossoff, Eric H.; Kuperman, Rachel; Kuzniecky, Ruben; Lowenstein, Daniel H.; McGuire, Shannon M.; Motika, Paul V.; Novotny, Edward J.; Ottman, Ruth; Paolicchi, Juliann M.; Parent, Jack; Park, Kristen; Poduri, Annapurna; Sadleir, Lynette; Scheffer, Ingrid E.; Shellhaas, Renée A.; Sherr, Elliott; Shih, Jerry J.; Singh, Rani; Sirven, Joseph; Smith, Michael C.; Sullivan, Joe; Thio, Liu Lin; Venkat, Anu; Vining, Eileen P.G.; Von Allmen, Gretchen K.; Weisenberg, Judith L.; Widdess-Walsh, Peter; Winawer, Melodie R.; Allen, Andrew S.; Berkovic, Samuel F.; Cossette, Patrick; Delanty, Norman; Dlugos, Dennis; Eichler, Evan E.; Epstein, Michael P.; Glauser, Tracy; Goldstein, David B.; Han, Yujun; Heinzen, Erin L.; Johnson, Michael R.; Kuzniecky, Ruben; Lowenstein, Daniel H.; Marson, Anthony G.; Mefford, Heather C.; Nieh, Sahar Esmaeeli; O’Brien, Terence J.; Ottman, Ruth; Petrou, Stephen; Petrovski, Slavé; Poduri, Annapurna; Ruzzo, Elizabeth K.; Scheffer, Ingrid E.; Sherr, Elliott

    2014-01-01

    Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the “classical” epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1 in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p = 8.2 × 10−4), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have an identifiable causal de novo mutation. Strikingly, 75% of mutations in these probands are predicted to disrupt a protein involved in regulating synaptic transmission, and there is a significant enrichment of de novo mutations in genes in this pathway in the entire cohort as well. These findings emphasize an important role for synaptic dysregulation in epileptic encephalopathies, above and beyond that caused by ion channel dysfunction. PMID:25262651

  8. Epileptic encephalopathy: Use and misuse of a clinically and conceptually important concept.

    PubMed

    Howell, Katherine B; Harvey, A Simon; Archer, John S

    2016-03-01

    The term epileptic encephalopathy (EE) denotes a process by which epileptic activity adversely affects brain function over and above the underlying etiology. Underlying mechanisms are poorly understood, but recent studies demonstrate that seizures and interictal epileptiform discharges can disrupt distributed neural networks that underpin cognitive functions, both temporarily and permanently. EE is just one of a number of factors that can affect development in epilepsy. The presence and relative contribution of EE to cognitive impairment is often difficult to separate from that of the underlying etiology or even effects of antiepileptic medication (AEM). This difficulty has led to the increasing use of the term EE to encapsulate "severe" epileptic syndromes, or etiologies associated with severe epilepsy and intellectual disability (ID), regardless of evidence that the epileptic process has impacted cognition. The use of the term EE in the literature to describe both the process of cognitive impairment by epileptic activity and as a category for severe epilepsy syndromes is creating confusion. We propose that use of the term EE be restricted to the central concept of a pervasive epileptic process disrupting development, and that the use of EE as a classifier be avoided. A different term is needed to encapsulate the broad and heterogenous group of patients with severe epilepsy and ID, for which the mechanisms may be unknown but are often closely related to the underlying genetic, metabolic, or structural etiology. An improved understanding of the mechanisms by which EE develops is of critical importance, potentially leading to identification of biomarkers for early detection and treatment. PMID:26778176

  9. Hippocampus and Retrograde Amnesia in the Rat Model: A Modest Proposal for the Situation of Systems Consolidation

    ERIC Educational Resources Information Center

    Sutherland, Robert J.; Sparks, Fraser T.; Lehmann, Hugo

    2010-01-01

    The properties of retrograde amnesia after damage to the hippocampus have been explicated with some success using a rat model of human medial temporal lobe amnesia. We review the results of this experimental work with rats focusing on several areas of consensus in this growing literature. We evaluate the theoretically significant hypothesis that…

  10. Hippocampus and amygdala volumes in patients with vaginismus

    PubMed Central

    Atmaca, Murad; Baykara, Sema; Ozer, Omer; Korkmaz, Sevda; Akaslan, Unsal; Yildirim, Hanefi

    2016-01-01

    AIM: To compare hippocampus and amygdala volumes of patients with vaginismus with those of healthy control subjects. METHODS: Magnetic resonance imaging was performed on ten patients with vaginismus and ten control subjects matched for age and gender. Volumes of the hippocampus and amygdala were blindly measured. RESULTS: We found that the mean right amygdala volume of patients with vaginismus were smaller than that of the healthy controls. With regard to hippocampus volumes, the mean left and right hippocampus volumes were smaller than those of the healthy controls. CONCLUSION: Our present findings suggest that there have been hippocampus and amygdala structural abnormalities in patients with vaginismus. These changes provide the notion that vaginismus may be a fear-related condition. PMID:27354964

  11. The T-type calcium channel antagonist Z944 disrupts prepulse inhibition in both epileptic and non-epileptic rats.

    PubMed

    Marks, Wendie N; Greba, Quentin; Cain, Stuart M; Snutch, Terrance P; Howland, John G

    2016-09-22

    The role of T-type calcium channels in brain diseases such as absence epilepsy and neuropathic pain has been studied extensively. However, less is known regarding the involvement of T-type channels in cognition and behavior. Prepulse inhibition (PPI) is a measure of sensorimotor gating which is a basic process whereby the brain filters incoming stimuli to enable appropriate responding in sensory rich environments. The regulation of PPI involves a network of limbic, cortical, striatal, pallidal and pontine brain areas, many of which show high levels of T-type calcium channel expression. Therefore, we tested the effects of blocking T-type calcium channels on PPI with the potent and selective T-type antagonist Z944 (0.3, 1, 3, 10mg/kg; i.p.) in adult Wistar rats and two related strains, the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and Non-Epileptic Control (NEC). PPI was tested using a protocol that varied prepulse intensity (3, 6, and 12dB above background) and prepulse-pulse interval (30, 50, 80, 140ms). Z944 decreased startle in the Wistar strain at the highest dose relative to lower doses. Z944 dose-dependently disrupted PPI in the Wistar and GAERS strains with the most potent effect observed with the higher doses. These findings suggest that T-type calcium channels contribute to normal patterns of brain activity that regulate PPI. Given that PPI is disrupted in psychiatric disorders, future experiments that test the specific brain regions involved in the regulation of PPI by T-type calcium channels may help inform therapeutic development for those suffering from sensorimotor gating impairments. PMID:27365170

  12. Generalised stunting of roots in an epileptic child: is long-term phenytoin therapy the cause?

    PubMed Central

    Jindal, Garima; Pandey, Ramesh K; Kumar, Dipanshu

    2012-01-01

    Long-term phenytoin therapy is known to cause disturbance in calcium and bone homeostasis. Dental tissues being calcified tissues can also be affected by this derangement of mineral metabolism, especially during developmental phases. This report describes a case of an epileptic child who presented with short roots, enlarged pulp chambers, blunt apices and delayed eruption of permanent dentition, which might be attributed to long-term phenytoin therapy. The purpose of this case report is to increase awareness among the clinicians about its possible dental implications and emphasise upon the need of regular dental check-ups in epileptic children. PMID:22761220

  13. [Psychogenic non-epileptic seizures: issues of comorbidity in the diagnosis and treatment].

    PubMed

    Nikolaev, E L; Serli, T; Rezvyi, G

    2016-01-01

    The paper presents a case report of seizures in a man of 40 years who was assessed by neurologists and psychiatrists for 15 years. Due to the low efficacy of treatment and permanent health deterioration, the patient was recognized as disabled. Later initial diagnosis of psychogenic non-epileptic seizures was completed by comorbid diagnosis of bipolar affective disorder, type II. Treatment with lamotrigine improved the patient's condition. It has been regarded as a positive effect on organic changes in the brain that are associated with affective and epileptic disorders. PMID:27240050

  14. Early epileptic encephalopathies including West syndrome: a 3-year retrospective study from Klang Hospital, Malaysia.

    PubMed

    Thambyayah, M

    2001-11-01

    It is difficult to give a country report from Malaysia. A study done in 1999 reported the incidence of West Syndrome to be 3% among newly diagnosed cases of epilepsy. In this 3 year retrospective hospital-based study (1997-1999), the prevalence of early epileptic encephalopathy (EEE) and West Syndrome were 4.1 and 2.5% respectively. There is difficulty classifying EEE cases into distinct sub-groups of EIEE (early infantile epileptic encephalopathy), WS (West Syndrome) and SMEI (severe myoclonic epilepsy of infancy), using a combination of clinical features, EEG and CT/MRI findings. PMID:11701263

  15. Canine and feline epileptic seizures and the lunar cycle: 2,507 seizures (2000-2008).

    PubMed

    Browand-Stainback, Laura; Levesque, Donald; McBee, Matthew

    2011-01-01

    Epileptic seizures in 211 canine and feline patients diagnosed with idiopathic epilepsy were evaluated for temporal significance in relation to the lunar cycle. Seizure counts were compared among each of the eight individual lunar phases, among each of eight exact lunar phase dates, and by percent of lunar illumination using generalized estimating equations. No statistical significance was found in any of these comparisons excluding a relationship between the onset of epileptic seizures and the phases of the moon. Alteration in anticonvulsant treatment or monitoring of canine and feline patients with idiopathic epilepsy at large was not warranted based on the lunar cycle. PMID:21852516

  16. Influence of chronic amphetamine treatment and acute withdrawal on serotonin synthesis and clearance mechanisms in the rat ventral hippocampus.

    PubMed

    Barr, Jeffrey L; Scholl, Jamie L; Solanki, Rajeshwari R; Watt, Michael J; Lowry, Christopher A; Renner, Kenneth J; Forster, Gina L

    2013-02-01

    Amphetamine withdrawal in both humans and rats is associated with increased anxiety states, which are thought to contribute to drug relapse. Serotonin in the ventral hippocampus mediates affective behaviors, and reduced serotonin levels in this region are observed in rat models of high anxiety, including during withdrawal from chronic amphetamine. This goal of this study was to understand the mechanisms by which reduced ventral hippocampus serotonergic neurotransmission occurs during amphetamine withdrawal. Serotonin synthesis (assessed by accumulation of serotonin precursor as a measure of the capacity of in vivo tryptophan hydroxylase activity), expression of serotonergic transporters, and in vivo serotonergic clearance using in vivo microdialysis were assessed in the ventral hippocampus in adult male Sprague Dawley rats at 24 h withdrawal from chronic amphetamine. Overall, results showed that diminished extracellular serotonin at 24 h withdrawal from chronic amphetamine was not accompanied by a change in capacity for serotonin synthesis (in vivo tryptophan hydroxylase activity), or serotonin transporter expression or function in the ventral hippocampus, but instead was associated with increased expression and function of organic cation transporters (low-affinity, high-capacity serotonin transporters). These findings suggest that 24 h withdrawal from chronic amphetamine reduces the availability of extracellular serotonin in the ventral hippocampus by increasing organic cation transporter-mediated serotonin clearance, which may represent a future pharmacological target for reversing anxiety states during drug withdrawal. PMID:23157166

  17. Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy

    PubMed Central

    Miller-Delaney, Suzanne F.C.; Bryan, Kenneth; Das, Sudipto; McKiernan, Ross C.; Bray, Isabella M.; Reynolds, James P.; Gwinn, Ryder; Stallings, Raymond L.

    2015-01-01

    Temporal lobe epilepsy is associated with large-scale, wide-ranging changes in gene expression in the hippocampus. Epigenetic changes to DNA are attractive mechanisms to explain the sustained hyperexcitability of chronic epilepsy. Here, through methylation analysis of all annotated C-phosphate-G islands and promoter regions in the human genome, we report a pilot study of the methylation profiles of temporal lobe epilepsy with or without hippocampal sclerosis. Furthermore, by comparative analysis of expression and promoter methylation, we identify methylation sensitive non-coding RNA in human temporal lobe epilepsy. A total of 146 protein-coding genes exhibited altered DNA methylation in temporal lobe epilepsy hippocampus (n = 9) when compared to control (n = 5), with 81.5% of the promoters of these genes displaying hypermethylation. Unique methylation profiles were evident in temporal lobe epilepsy with or without hippocampal sclerosis, in addition to a common methylation profile regardless of pathology grade. Gene ontology terms associated with development, neuron remodelling and neuron maturation were over-represented in the methylation profile of Watson Grade 1 samples (mild hippocampal sclerosis). In addition to genes associated with neuronal, neurotransmitter/synaptic transmission and cell death functions, differential hypermethylation of genes associated with transcriptional regulation was evident in temporal lobe epilepsy, but overall few genes previously associated with epilepsy were among the differentially methylated. Finally, a panel of 13, methylation-sensitive microRNA were identified in temporal lobe epilepsy including MIR27A, miR-193a-5p (MIR193A) and miR-876-3p (MIR876), and the differential methylation of long non-coding RNA documented for the first time. The present study therefore reports select, genome-wide DNA methylation changes in human temporal lobe epilepsy that may contribute to the molecular architecture of the epileptic brain. PMID

  18. Association between Income and the Hippocampus

    PubMed Central

    Hanson, Jamie L.; Chandra, Amitabh; Wolfe, Barbara L.; Pollak, Seth D.

    2011-01-01

    Facets of the post-natal environment including the type and complexity of environmental stimuli, the quality of parenting behaviors, and the amount and type of stress experienced by a child affects brain and behavioral functioning. Poverty is a type of pervasive experience that is likely to influence biobehavioral processes because children developing in such environments often encounter high levels of stress and reduced environmental stimulation. This study explores the association between socioeconomic status and the hippocampus, a brain region involved in learning and memory that is known to be affected by stress. We employ a voxel-based morphometry analytic framework with region of interest drawing for structural brain images acquired from participants across the socioeconomic spectrum (n = 317). Children from lower income backgrounds had lower hippocampal gray matter density, a measure of volume. This finding is discussed in terms of disparities in education and health that are observed across the socioeconomic spectrum. PMID:21573231

  19. A role for dorsal and ventral hippocampus in response learning.

    PubMed

    Fidalgo, C; Conejo, N M; González-Pardo, H; Lazo, P S; Arias, J L

    2012-07-01

    The hippocampus and the striatum have been traditionally considered as part of different and independent memory systems despite growing evidence supporting that both brain regions may even compete for behavioral control in particular learning tasks. In this regard, it has been reported that the hippocampus could be necessary for the use of idiothetic cues in several types of spatial learning tasks. Accordingly, the ventral striatum receives strong anatomical projections from the hippocampus, suggesting a participation of both regions in goal-directed behavior. Our work examined the role of the dorsal and ventral hippocampus on a response learning task. Cytochrome c oxidase (C.O.) quantitative histochemistry was used as an index of brain oxidative metabolism. In addition, determination of C.O. subunit I levels in the hippocampus by western blot analysis was performed to assess the contribution of this subunit to overall C.O. activity. Increased brain oxidative metabolism was found in most of the studied hippocampal subregions when experimental group was compared with a swim control group. However, no differences were found in the amount of C.O. subunit I expressed in the hippocampus by western blot analysis. Our results support that both the dorsal and ventral hippocampus are associated with the use of response strategies during response learning. PMID:22507525

  20. Amino acid changes in a genetic strain of epileptic beagle dogs.

    PubMed

    van Gelder, N M; Edmonds, H L; Hegreberg, G A; Chatburn, C C; Clemmons, R M; Sylvester, D M

    1980-11-01

    A neurochemical evaluation of beagle dogs with naturally occurring spontaneous generalized convulsive seizures was performed. Amino acid profiles of serum, cerebrospinal fluid (CSF), and biopsied cerebral cortex from epileptic dogs were compared with those from seizure-free siblings. No differences in absolute levels were noted. However, when levels were normalized as a percent of total free amino acids, seizures was performed. Amino acid profiles of serum, cerebrospinal fluid (CEF), and biopsied cerebral cortex from epileptic dogs were compared with those seizure-free siblings. No differences also the two groups differed in certain respects. Ten significant correlations between amino acid pairs appeared in epileptic dogs, but only one was seen in seizure-free animals. Seven of these ten correlations involved glutamate or taurine. It was noted that the highly correlated amino acids (taurine, glutamate, glycine, glutamine, alanine) all utilize sodium-dependent membrane transport processes. The sum of glutamate, aspartate, and glycine levels (competing sodium-dependent high-affinity systems) was significantly lower in epileptic beagles. Since this difference was noted in serum but not CSF or brain, it may indicate a diminished capacity of sodium-dependent high-affinity renal transport for acidic and certain small neutral amino acids. PMID:6778970

  1. [Correlation between the regional blood volume and epileptic seizures in Papio papio].

    PubMed

    Ancri, D; Naquet, R; Basset, J Y; Ménini, C; Lonchampt, M F; Meldrum, B S; Stutzmann, J M

    1979-07-16

    The method of labelling red cells with technetium-99m was used to measured regional blood volume auring different types of epileptic seizures induced in the Baboon Papio papio. During seizures the cerebral blood volume increases and there is simultaneously a decrease of blood volume in nasal and hepatic regions, and a transitory increase of blood volume in the forepaws. PMID:117933

  2. A Project to Vocationally Rehabilitate Persons with Poorly Controlled Epileptic Seizures.

    ERIC Educational Resources Information Center

    Phelps, William R.

    This three-year pilot program provided an opportunity to work intensively with a small group of severe epileptic clients in a comprehensive rehabilitation center setting. The goals of the program were not only to evaluate intensively and attempt to maximize the individual client's potential for working and living in society through the provision…

  3. The Persistence of Erroneous Familiarity in an Epileptic Male: Challenging Perceptual Theories of Deja Vu Activation

    ERIC Educational Resources Information Center

    O'Connor, Akira R.; Moulin, Christopher J. A.

    2008-01-01

    We report the case of a 39-year-old, temporal lobe epileptic male, MH. Prior to complex partial seizure, experienced up to three times a day, MH often experiences an aura experienced as a persistent sensation of deja vu. Data-driven theories of deja vu formation suggest that partial familiarity for the perceived stimulus is responsible for the…

  4. Epileptic Encephalopathies and Their Relationship to Developmental Disorders: Do Spikes Cause Autism?

    ERIC Educational Resources Information Center

    Tharp, Barry R.

    2004-01-01

    Epileptic encephalopathies are progressive clinical and electroencephalographic syndromes where deterioration is thought to be caused by frequent seizures and abundant EEG epileptiform activity. Seizures occur in approximately 10-15% of children with pervasive developmental disorders (PDD) and 8-10% have epileptiform EEG abnormalities without…

  5. Epileptic nystagmus: description of a pediatric case with EEG correlation and SPECT findings.

    PubMed

    Nicita, F; Papetti, L; Spalice, A; Ursitti, F; Massa, R; Properzi, E; Iannetti, P

    2010-11-15

    Epileptic nystagmus (EN) describes repetitive eye movements that result from seizure activity. We describe a patient with EN and vertigo first noted at the age of 4 yr and 10 mo. Brain MRI did not show anomalies. Ictal EEG recordings revealed epileptic activity during three episodes of horizontal, left-beating nystagmus not crossing the midline. Ictal 99mTc-ECD SPECT demonstrated the presence of active foci in multiple cerebral regions including bilateral prefrontal, bilateral parieto-temporo-occipital and the left parieto-insular-vestibular areas. A wide area of hypoperfusion was also evident in the right hemisphere, prevailing in the parieto-occipital regions and the medial prefrontal gyrus. Topiramate was started at a dose of 2 mg/kg/d with complete seizure control after 14 d. EEG and SPECT were repeated after a seizure-free period of 1 mo; disappearance of epileptic activity and modification of cerebral perfusion were evident. This case reaffirms the cortical origin and involvement of temporo-occipital and frontal cortex in the genesis of saccadic epileptic nystagmus. Rapid complete control of clinical events coincided with the normalization of EEG and improvement of the SPECT pattern. PMID:20832824

  6. Cognitive-Behavioral Treatment of Depressed Affect among Epileptics: Preliminary Findings.

    ERIC Educational Resources Information Center

    Davis, Gay R.; And Others

    1984-01-01

    Evaluated a program where cognitive-behavioral methods were utilized in a structured learning format with clinically depressed epileptics (N=13). Results indicated that cognitive behavioral interventions result in significant decreases in depression and increases in related areas of psychosocial functioning that are maintained over time. (LLL)

  7. Sex hormones, sexual activity and plasma anticonvulsant levels in male epileptics.

    PubMed Central

    Toone, B K; Wheeler, M; Nanjee, M; Fenwick, P; Grant, R

    1983-01-01

    Testosterone, LH, FSH, PRL, and sex hormone binding globulin (SHBG) were measured in 72 male epileptic patients on chronic anticonvulsant drug regimes. Sexual activity was estimated and plasma anticonvulsants measured. Total testosterone (TT), LH, FSH, PRL, and SHBG were increased; free testosterone (FT) was decreased. Sexual activity appeared diminished particularly in relation to reduced FT. PMID:6413659

  8. Effect of Anti-Epileptic Drugs on Serum Level of IgG Subclasses

    PubMed Central

    Ashrafi, Mahmoud-Reza; Hosseini, Seyed-Ahmad; Biglari, Mohammad; Abolmaali, Sarah; Azizi Malamiri, Reza; Mombeini, Hoda; Pourpak, Zahra; Saladjegheh, Narges; Rezaei, Nima; Samadian, Azam; Aghamohammadi, Asghar

    2010-01-01

    Objective There are some controversial studies on effects of anti-epileptic drugs (AEDs) on serum IgG subclasses; however, the role of these medications is still unclear. The aim of this study was evaluation the effects of anti-epileptic drugs on serum concentration of IgG and its subclasses Methods Serum IgG and IgG subclasses of 61 newly diagnosed epileptic patients were measured at the beginning of monotherapy with carbamazepine, sodium valproate, and phenobarbital, and 6 months later. Measurement of IgG and its subclasses was performed using nephlometry and ELISA techniques, respectively. Findings Reduction of at least one IgG subclass was found in 6 patients 6 months after treatment with AEDs. Among 27 patients receiving carbamazepine, decrease in at least one serum IgG subclass level was found in 5 patients. Among 20 patients using sodium valproate, only one patient showed decrease in IgG2 subclass. None of the 14 patients using phenobarbital revealed significant decrease in IgG subclasses. No infection was seen in the patients with reduction of subclasses. Conclusion Although in our study, children with selective IgG subclass deficiency were asymptomatic, assessment of serum immunoglobulin levels could be recommended at starting the administration of AEDs and in serial intervals afterward in epileptic patients. PMID:23056716

  9. Psychosocial Functioning of Adult Epileptic and MS Patients and Adult Normal Controls on the WPSI.

    ERIC Educational Resources Information Center

    Tan, Siang-Yang

    1986-01-01

    Psychosocial functioning of adult epileptic outpatients as assessed by the Washington Psychosocial Seizure Inventory (WPSI) was compared to that of adult multiple sclerosis (MS) outpatients and normal subjects. When only valid WPSI profiles were considered, the only significant finding was that the epilepsy group and the MS group had more…

  10. Mozart k.545 mimics mozart k.448 in reducing epileptiform discharges in epileptic children.

    PubMed

    Lin, Lung-Chang; Lee, Mei-Wen; Wei, Ruey-Chang; Mok, Hin-Kiu; Wu, Hui-Chuan; Tsai, Chin-Lin; Yang, Rei-Cheng

    2012-01-01

    Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect. Our previous work reveals positive effects of Mozart K.448 in reducing epileptiform discharges in epileptic children. In this study, we evaluated the effect of Mozart K.545 and compared the effects with those of Mozart K.448 on epileptiform discharges in children with epilepsy. Thirty-nine epileptic children with epileptiform discharges were included in the study. They received electroencephalogram examinations before, during, and after listening to Mozart K.448 and K.545, one week apart, respectively. The frequencies of epileptiform discharges were compared. There was a significant decrease in the frequency of epileptiform discharges during and right after listening to Mozart K.448 and K.545 (reduced by 35.7 ± 32.7% during Mozart K.448 and 30.3 ± 44.4% after Mozart K.448; and 34.0 ± 39.5% during Mozart K.545 and 31.8 ± 39.2% after Mozart K.545). Spectrogrammatic analysis of the two pieces of music demonstrated that both share similar spectrogrammatic characteristics. Listening to Mozart K.448 and K.545 decreased the epileptiform discharges in epileptic children. This suggests that Mozart K.448 is not the only piece of music to have beneficial effects on children with epilepsy. Other music with lower harmonics may also decrease epileptiform discharges in epileptic children. PMID:23304207

  11. Aura and post-ictal headache in epileptic patients treated with flunarizine.

    PubMed

    Binnie, C D; Overweg, J

    1986-01-01

    Flunarizine is effective for the prophylaxis of both migraine attacks and epileptic seizures. Of 77 patients treated with flunarizine for intractable epilepsy, 28 had an aura preceding their seizures. In 22 this disappeared on flunarizine administration. Of 14 subject to post-ictal headache, 13 reported relief of this symptom on flunarizine. PMID:3609881

  12. Verbal Memory Compensation: Application to Left and Right Temporal Lobe Epileptic Patients

    ERIC Educational Resources Information Center

    Bresson, Christel; Lespinet-Najib, Veronique; Rougier, Alain; Claverie, Bernard; N'Kaoua, Bernard

    2007-01-01

    This study investigates the compensatory impact of cognitive aids on left and right temporal lobe epileptic patients suffering from verbal memory disorders, who were candidates for surgery. Cognitive aids are defined in the levels-of-processing framework and deal with the depth of encoding, the elaboration of information, and the use of retrieval…

  13. Epileptic Seizure Detection in Eeg Signals Using Multifractal Analysis and Wavelet Transform

    NASA Astrophysics Data System (ADS)

    Uthayakumar, R.; Easwaramoorthy, D.

    2013-06-01

    This paper explores the three different methods to explicitly recognize the healthy and epileptic EEG signals: Modified, Improved, and Advanced forms of Generalized Fractal Dimensions (GFD). The newly proposed scheme is based on GFD and the discrete wavelet transform (DWT) for analyzing the EEG signals. First EEG signals are decomposed into approximation and detail coefficients using DWT and then GFD values of the original EEGs, approximation and detail coefficients are computed. Significant differences are observed among the GFD values of the healthy and epileptic EEGs allowing us to classify seizures with high accuracy. It is shown that the classification rate is very less accurate without DWT as a preprocessing step. The proposed idea is illustrated through the graphical and statistical tools. The EEG data is further tested for linearity by using normal probability plot and we proved that epileptic EEG had significant nonlinearity whereas healthy EEG distributed normally and similar to Gaussian linear process. Therefore, we conclude that the GFD and the wavelet decomposition through DWT are the strong indicators of the state of illness of epileptic patients.

  14. [The role of the nurse in the patient education of young epileptic patients].

    PubMed

    Danse, Marion; Goujon, Estelle

    2015-01-01

    An epileptic seizure in a child is a major source of anxiety and turns the family's everyday life upside down. Through therapeutic education, the nurse guides the families towards the autonomous management of the seizures, antiepileptic treatments, adaptations to daily life and potential comorbidities. PMID:26100481

  15. Age Related Personality Characteristics of Epileptic Children: Parent and Child Reports.

    ERIC Educational Resources Information Center

    Kralj, M. M.; And Others

    Personality characteristics of 101 epileptic children in two age groups (5-11 and 11-16) were studied by means of the child-reported Missouri Children's Picture Series and the mother-reported Missouri Problem Behavior Checklist. Scores for each age group across both parent and child reports were compared to published norms. A one-way multivariate…

  16. Oxidative Stress Measurement and Prediction of Epileptic Seizure in Children and Adults With Severe Motor and Intellectual Disabilities

    PubMed Central

    Morimoto, Masahito; Satomura, Shigeko; Hashimoto, Toshiaki; Ito, Etsuro; Kyotani, Shojiro

    2016-01-01

    Background The medical care of severe motor and intellectual disabilities (SMID) depends on the empirical medical care. Epileptic seizure specific to SMID is difficult to suppress using anti-epileptic drugs, and its tendency to persist for long periods poses an issue. The present study was undertaken to evaluate the relationship between epileptic seizure in cases with SMID and oxidative stress in the living body by examining endogenous antioxidants, the degree of oxidation (reactive oxygen metabolites (d-ROMs)), and the biological antioxidant potential (BAP) as indicators. Methods Target patients were 43 SMID epilepsy patients. Blood was sampled before breakfast and medication. As for the specimen, d-ROMs and BAP were measured using the free radical analyzer. Results The present study did not reveal any correlation between endogenous antioxidants (albumin) and the frequency of epileptic seizures. On the other hand, d-ROMs were correlated with the frequency of epileptic seizure. In particular, strong correlations between the frequency of epileptic seizures and the d-ROMs/BAP ratio as well as the BAP/d-ROMs ratio were noted. Conclusions These results indicate that the use of d-ROMs and BAP as biomarkers can provide a tool for predicting the prognosis of epileptic seizures in patients with SMID. PMID:27222671

  17. The differences in epileptic characteristics in patients with porencephaly and schizencephaly.

    PubMed

    Shimizu, Miki; Maeda, Tomoki; Izumi, Tatsuro

    2012-08-01

    The epileptic characteristics and their differences in patients with porencephaly and schizencephaly were, respectively, evaluated. Eleven patients with porencephaly and eight patients with schizencephaly were retrospectively enrolled in this study. Five of the six patients with extensive porencephaly and all five patients with open-lip schizencephaly had been suffering from various types of epileptic seizures. Three patients with extensive porencephaly and all five patients with open-lip schizencephaly had presented with early onset seizures before 9 months of age. Two patients with extensive porencephaly and three patients with open-lip schizencephaly had presented with West syndrome. These two groups of patients with epileptic seizures showed generalized epilepsy or generalized epilepsy with unilateral dominancy at the onset, and then developed localization-related epilepsy or unilateral seizures with increasing age. The epileptic paroxysms showed multifocal independent spikes, which were not always localized in the defect or cleft sites at the last examination. Polytherapy or synergistic combinations were eventually introduced for these intractable seizures in both groups for patients without any evidence of efficacy. In the porencephaly patients, four of five patients achieved good seizure control with appropriate monotherapy or two-drug therapy including valproate. All five patients with schizencephaly had been treated by polytherapy, and three of them had persistent intractable seizures in spite of trying rational monotherapy or two-drug therapy. The epileptic intractability associated with open-lip schizencephaly might be related to the epileptogenesis of these extensive and widespread defective lesions, which were commonly associated with cortical dysplasia. A trial of rational monotherapy or two-drug therapy may be effective, rather than larger-number polytherapy in many cases, more in porencephaly than schizencephaly. PMID:22024697

  18. Neurophysiological activity underlying altered brain metabolism in epileptic encephalopathies with CSWS.

    PubMed

    De Tiège, Xavier; Trotta, Nicola; Op de Beeck, Marc; Bourguignon, Mathieu; Marty, Brice; Wens, Vincent; Nonclercq, Antoine; Goldman, Serge; Van Bogaert, Patrick

    2013-08-01

    We investigated the neurophysiological correlate of altered regional cerebral glucose metabolism observed in children with epileptic encephalopathy with continuous spike-waves during sleep (CSWS) by using a multimodal approach combining time-sensitive magnetic source imaging (MSI) and positron emission tomography with [(18)F]-fluorodeoxyglucose (FDG-PET). Six patients (4 boys and 2 girls, age range: 4-8 years, 3 patients with Landau-Kleffner syndrome (LKS), 3 patients with atypical rolandic epilepsy (ARE)) were investigated by FDG-PET and MSI at the acute phase of CSWS. In all patients, the onset(s) of spike-waves discharges were associated with significant focal hypermetabolism. The propagation of epileptic discharges to other brain areas was associated with focal hypermetabolism (five patients), hypometabolism (one patient) or the absence of any significant metabolic change (one patient). Interestingly, most of the hypometabolic areas were not involved in the epileptic network per se. This study shows that focal hypermetabolism observed at the acute phase of CSWS are related to the onset or propagation sites of spike-wave discharges. Spike-wave discharges propagation can be associated to other types of metabolic changes, suggesting the occurrence of various neurophysiological mechanisms at the cellular level. Most of the hypometabolic areas are not involved in the epileptic network as such and are probably related to a mechanism of remote inhibition. These findings highlight the critical value of combining FDG-PET with time-sensitive functional neuroimaging approaches such as MSI to assess CSWS epileptic network when surgery is considered as a therapeutic approach. PMID:23561286

  19. Patterns of the UP-Down state in normal and epileptic mice.

    PubMed

    Bragin, A; Benassi, S K; Engel, J

    2012-12-01

    Goal of this manuscript is to investigate whether changes that exist in epileptic brain generating spontaneous seizures are reflected in the pattern of the UP-Down state (UDS) recorded from the neocortex and dentate gyrus. Experiments were carried out on naive and epileptic mice under urethane anesthesia. Local field potentials were recorded with chronically implanted microelectrodes and single unit activity was recorded with glass microelectrodes. Recorded neurons were labeled by neurobiotin and identified later as granular cells or interneurons in histological sections. The following major features differentiate the pattern of UDS in epilepsy from normal. (1) The duration of UP and Down phases is significantly longer. (2) Recovery of network excitability after termination of the UP phase is longer. (3) UP-spikes occur during the UP phase, which transiently interrupt the development of the normal electrographic pattern of UP phase. Our data provide evidence that UP-spikes result from gigantic EPSPs generated in response to afferent activity. UP-spikes in the neocortex and dentate gyrus occur in close temporal relationship indicating the existence of direct or indirect pathological functional connections between these areas. Changes in the duration of UP and Down phases as well increased time of recovery of excitability of epileptic brain after termination of UP phase suggest alterations in the homeostatic properties of neuronal network in epileptic brain. We suggest that the existence of UP-spikes in epileptic brain may be an additional electrographic pattern indicating epileptogenicity. Unraveling the neuronal substrates of UP-spikes may further improve our understanding of the mechanisms of epilepsy. PMID:22960310

  20. Frequency of Toxoplasma and Toxocara Sp. Antibodies in Epileptic Patients, in South Western Iran

    PubMed Central

    ALLAHDIN, Sudabeh; KHADEMVATAN, Shahram; RAFIEI, Abdollah; MOMEN, Aliakbar; RAFIEI, Reza

    2015-01-01

    Objective Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate seizures. Infectious agents are mentioned in its etiology. With identifying and appropriate treatment of these infectious agents, preventing their secondary outcomes, including seizure is possible. This study was conducted to determine frequency of anti-Toxoplasma antibodies (IgG, IgM) and anti-Toxocara antibody (IgG) in epileptic patients. Materials & Methods Study sample consisted of 141 epileptic patients and 144 healthy people. After obtaining informed consents and completing demographic questionnaire, serum samples were taken from participants. The diagnostic test of Toxoplasma IgG & IgM and Toxocara antibodies was performed under the same conditions using ELISA method in a qualified private laboratory. Samples from patients and control groups with positive ELISA test in terms of anti-Toxocara antibody were also used for confirmatory Western blot test. Result According to ELISA results, 28 (19.85%) epileptic patients and 2(1.38%) of healthy people had anti-Toxocara antibodies (P<001), while 39 (30.46%) of the control group people and 14.18% of patients had anti-Toxoplsma antibodies (P=0.001). Conclusion Frequency of anti-Toxoplasma gondii is lower in epileptic than healthy individuals and this result is contrary to investigations that have reported higher levels of this antibody in such patient groups. ELISA results for Toxocara showed that the frequency of anti-Toxocara antibody in epileptic patients might empower the probability that this parasite may cause central nervous system damage. Western blotting has high specificity and is a proper confirmative method for diagnosis of toxocariasis. PMID:26664439

  1. Postnatal development of the hippocampus in the Rhesus macaque (Macaca mulatta): a longitudinal magnetic resonance imaging study.

    PubMed

    Hunsaker, Michael R; Scott, Julia A; Bauman, Melissa D; Schumann, Cynthia M; Amaral, David G

    2014-07-01

    Nonhuman primates are widely used models to investigate the neural substrates of human behavior, including the development of higher cognitive and affective function. Due to their neuroanatomical and behavioral homologies with humans, the rhesus macaque monkey (Macaca mulatta) provides an excellent animal model in which to characterize the maturation of brain structures from birth through adulthood and into senescence. To evaluate hippocampal development in rhesus macaques, structural magnetic resonance imaging scans were obtained longitudinally at 9 time points between 1 week and 260 weeks (5 years) of age on 24 rhesus macaque monkeys (12 males, 12 females). In our sample, the hippocampus reaches 50% of its adult volume by 13 weeks of age and reaches an adult volume by 52 weeks in both males and females. The hippocampus appears to be slightly larger at 3 years than at 5 years of age. Male rhesus macaques have larger hippocampi than females from 8 weeks onward by approximately 5%. Interestingly, there was increased variability in hemispheric asymmetry for hippocampus volumes at younger ages than at later ages. These data provide a comprehensive evaluation of the longitudinal development of male and female rhesus macaque hippocampus across development from 1 week to 5 years of age. PMID:24648155

  2. Postnatal Development of the Hippocampus in the Rhesus Macaque (Macaca mulatta): A Longitudinal Magnetic Resonance Imaging Study

    PubMed Central

    Hunsaker, Michael R.; Scott, Julia A.; Bauman, Melissa D.; Schumann, Cynthia M.; Amaral, David G.

    2014-01-01

    Nonhuman primates are widely used models to investigate the neural substrates of human behavior, including the development of higher cognitive and affective function. Due to their neuroanatomical and behavioral homologies with humans, the rhesus macaque monkey (Macaca mulatta) provides an excellent animal model in which to characterize the maturation of brain structures from birth through adulthood and into senescence. To evaluate hippocampal development in rhesus macaques, structural magnetic resonance imaging scans were obtained longitudinally at 9 time points between 1 week and 260 weeks (5 years) of age on 24 rhesus macaque monkeys (12 male, 12 female). In our sample, the hippocampus reaches 50% of its adult volume by 13 weeks of age and reaches an adult volume by 52 weeks in both males and females. The hippocampus appears to be slightly larger at 3 years than at 5 years of age. Male rhesus macaques have larger hippocampi than females from 8 weeks onward by approximately 5%. Interestingly, there was increased variability in hemispheric asymmetry for hippocampus volumes at younger ages than at later ages. These data provide a comprehensive evaluation of the longitudinal development of male and female rhesus macaque hippocampus across development from 1 week to 5 years of age. PMID:24648155

  3. COMPENSATORY CHANGES IN THE HIPPOCAMPUS FOLLOWING INTRADENTATE INFUSION OF COLCHICINE

    EPA Science Inventory

    Direct infusion of colchicine into the dentate gyrus of the hippocampus kills granule cells and elicits compensatory behavioral, neurochemical and neuroanatomical changes. olchicine-treated rats are less sensitive to the behavioral effects of cholinergic muscarinic receptor antag...

  4. Statistical learning of temporal community structure in the hippocampus

    PubMed Central

    Schapiro, Anna C.; Turk-Browne, Nicholas B.; Norman, Kenneth A.; Botvinick, Matthew M.

    2015-01-01

    The hippocampus is involved in the learning and representation of temporal statistics, but little is understood about the kinds of statistics it can uncover. Prior studies have tested various forms of structure that can be learned by tracking the strength of transition probabilities between adjacent items in a sequence. We test whether the hippocampus can learn higher-order structure using sequences that have no variance in transition probability and instead exhibit temporal community structure. We find that the hippocampus is indeed sensitive to this form of structure, as revealed by its representations, activity dynamics, and connectivity with other regions. These findings suggest that the hippocampus is a sophisticated learner of environmental regularities, able to uncover higher-order structure that requires sensitivity to overlapping associations. PMID:26332666

  5. Additive genetic effect of APOE and BDNF on hippocampus activity.

    PubMed

    Kauppi, Karolina; Nilsson, Lars-Göran; Persson, Jonas; Nyberg, Lars

    2014-04-01

    Human memory is a highly heritable polygenic trait with complex inheritance patterns. To study the genetics of memory and memory-related diseases, hippocampal functioning has served as an intermediate phenotype. The importance of investigating gene-gene effects on complex phenotypes has been emphasized, but most imaging studies still focus on single polymorphisms. APOE ε4 and BDNF Met, two of the most studied gene variants for variability in memory performance and neuropsychiatric disorders, have both separately been related to poorer episodic memory and altered hippocampal functioning. Here, we investigated the combined effect of APOE and BDNF on hippocampal activation (N=151). No non-additive interaction effects were seen. Instead, the results revealed decreased activation in bilateral hippocampus and parahippocampus as a function of the number of APOE ε4 and BDNF Met alleles present (neither, one, or both). The combined effect was stronger than either of the individual effects, and both gene variables explained significant proportions of variance in BOLD signal change. Thus, there was an additive gene-gene effect of APOE and BDNF on medial temporal lobe (MTL) activation, showing that a larger proportion of variance in brain activation attributed to genetics can be explained by considering more than one gene variant. This effect might be relevant for the understanding of normal variability in memory function as well as memory-related disorders associated with APOE and BDNF. PMID:24321557

  6. Hippocampus ghrelin signaling mediates appetite through lateral hypothalamic orexin pathways

    PubMed Central

    Hsu, Ted M; Hahn, Joel D; Konanur, Vaibhav R; Noble, Emily E; Suarez, Andrea N; Thai, Jessica; Nakamoto, Emily M; Kanoski, Scott E

    2015-01-01

    Feeding behavior rarely occurs in direct response to metabolic deficit, yet the overwhelming majority of research on the biology of food intake control has focused on basic metabolic and homeostatic neurobiological substrates. Most animals, including humans, have habitual feeding patterns in which meals are consumed based on learned and/or environmental factors. Here we illuminate a novel neural system regulating higher-order aspects of feeding through which the gut-derived hormone ghrelin communicates with ventral hippocampus (vHP) neurons to stimulate meal-entrained conditioned appetite. Additional results show that the lateral hypothalamus (LHA) is a critical downstream substrate for vHP ghrelin-mediated hyperphagia and that vHP ghrelin activated neurons communicate directly with neurons in the LHA that express the neuropeptide, orexin. Furthermore, activation of downstream orexin-1 receptors is required for vHP ghrelin-mediated hyperphagia. These findings reveal novel neurobiological circuitry regulating appetite through which ghrelin signaling in hippocampal neurons engages LHA orexin signaling. DOI: http://dx.doi.org/10.7554/eLife.11190.001 PMID:26745307

  7. Building models for postmortem abnormalities in hippocampus of schizophrenics.

    PubMed

    Benes, Francine M

    2015-09-01

    Postmortem studies have suggested that there is abnormal GABAergic activity in the hippocampus in schizophrenia (SZ). In micro-dissected human hippocampal slices, a loss of interneurons and a compensatory upregulation of GABAA receptor binding activity on interneurons, but not PNs, has suggested that disinhibitory GABA-to-GABA connections are abnormal in stratum oriens (SO) of CA3/2, but not CA1, in schizophrenia. Abnormal expression changes in the expression of kainate receptor (KAR) subunits 5, 6 and 7, as well as an inwardly-rectifying hyperpolarization-activated cationic channel (Ih3; HCN3) may play important roles in regulating GABA cell activity at the SO CA3/2 locus. The exclusive neurons at this site are GABAergic interneurons; these cells also receive direct projections from the basolateral amygdala (BLA). When the BLA is stimulated by stereotaxic infusion of picrotoxin in rats, KARs influence axodendritic and presynaptic inhibitory mechanisms that regulate both inhibitory and disinhibitory interneurons in the SO-CA3/2 locus. The rat model described here was specifically developed to extend our understanding of these and other postmortem findings and has suggested that GABAergic abnormalities and possible disturbances in oscillatory rhythms may be related to a dysfunction of disinhibitory interneurons at the SO-CA3/2 site of schizophrenics. PMID:25749020

  8. Lentiviral-mediated delivery of Bcl-2 or GDNF protects against excitotoxicity in the rat hippocampus.

    PubMed

    Wong, Liang-Fong; Ralph, G Scott; Walmsley, Lucy E; Bienemann, Alison S; Parham, Stephen; Kingsman, Susan M; Uney, James B; Mazarakis, Nicholas D

    2005-01-01

    Nutrient deprivation during ischemia leads to severe insult to neurons causing widespread excitotoxic damage in specific brain regions such as the hippocampus. One possible strategy for preventing neurodegeneration is to express therapeutic proteins in the brain to protect against excitotoxicity. We investigated the utility of equine infectious anemia virus (EIAV)-based vectors as genetic tools for delivery of therapeutic proteins in an in vivo excitotoxicity model. The efficacy of these vectors at preventing cellular loss in target brain areas following excitotoxic insult was also assessed. EIAV vectors generated to overexpress the human antiapoptotic Bcl-2 or growth factor glial-derived neurotrophic factor (GDNF) genes protected against glutamate-induced toxicity in cultured hippocampal neurons. In an in vivo excitotoxicity model, adult Wistar rats received a unilateral dose of the glutamate receptor agonist N-methyl-D-aspartate to the hippocampus that induced a large lesion in the CA1 region. Neuronal loss could not be protected by prior transduction of a control vector expressing beta-galactosidase. In contrast, EIAV-mediated expression of Bcl-2 and GDNF significantly reduced lesion size thus protecting the hippocampus from excitotoxic damage. These results demonstrate that EIAV vectors can be effectively used to deliver putative neuroprotective genes to target brain areas and prevent cellular loss in the event of a neurological insult. Therefore these lentiviral vectors provide potential therapeutic tools for use in cases of acute neurotrauma such as cerebral ischemia. PMID:15585409

  9. Hippocampus-specific fMRI group activation analysis using the continuous medial representation.

    PubMed

    Yushkevich, Paul A; Detre, John A; Mechanic-Hamilton, Dawn; Fernández-Seara, María A; Tang, Kathy Z; Hoang, Angela; Korczykowski, Marc; Zhang, Hui; Gee, James C

    2007-05-01

    We present a new shape-based approach for regional group activation analysis in fMRI studies. The method restricts anatomical normalization, spatial smoothing and random effects statistical analysis to the space inside and around a structure of interest. Normalization involves finding intersubject correspondences between manually outlined masks, and it leverages the continuous medial representation, which makes it possible to extend surface-based shape correspondences to the space inside and outside of structures. Our approach is an alternative to whole-brain normalization in cases where the latter may fail due to anatomical variability or pathology. It also provides an opportunity to analyze the shape and thickness of structures concurrently with functional activation. We apply the technique to the hippocampus and evaluate it using data from a visual scene encoding fMRI study, where activation in the hippocampus is expected. We produce detailed statistical maps of hippocampal activation, as well as maps comparing activation inside and outside of the hippocampus. We find that random effects statistics computed by the new approach are more significant than those produced using the Statistical Parametric Mapping framework (Friston, K.J., Holmes, A.P., Worsley, K.J., Poline, J.-P., Firth, C.D., Frackowiak, R.S.J. 1994, Statistical parametric maps in functional imaging: a general linear approach. Human Brain Mapping, 2(4): 189-210) at low levels of smoothing, suggesting that greater specificity can be achieved by the new method without a severe tradeoff in sensitivity. PMID:17383900

  10. PACAP receptor gene polymorphism impacts fear responses in the amygdala and hippocampus

    PubMed Central

    Stevens, Jennifer Strafford; Almli, Lynn M.; Fani, Negar; Gutman, David A.; Bradley, Bekh; Norrholm, Seth D.; Reiser, Emily; Ely, Timothy D.; Dhanani, Rahim; Glover, Ebony M.; Jovanovic, Tanja; Ressler, Kerry J.

    2014-01-01

    We have recently found higher circulating levels of pituitary adenylate cyclase-activating polypeptide (PACAP) associated with posttraumatic stress disorder (PTSD) symptoms in a highly traumatized cohort of women but not men. Furthermore, a single nucleotide polymorphism in the PACAP receptor gene ADCYAP1R1, adenylate cyclase activating polypeptide 1 receptor type 1, was associated with individual differences in PTSD symptoms and psychophysiological markers of fear and anxiety. The current study outlines an investigation of individual differences in brain function associated with ADCYAP1R1 genotype. Forty-nine women who had experienced moderate to high levels of lifetime trauma participated in a functional MRI task involving passive viewing of threatening and neutral face stimuli. Analyses focused on the amygdala and hippocampus, regions that play central roles in the pathophysiology of PTSD and are known to have high densities of PACAP receptors. The risk genotype was associated with increased reactivity of the amygdala and hippocampus to threat stimuli and decreased functional connectivity between the amygdala and hippocampus. The findings indicate that the PACAP system modulates medial temporal lobe function in humans. Individual differences in ADCYAP1R1 genotype may contribute to dysregulated fear circuitry known to play a central role in PTSD and other anxiety disorders. PMID:24516127

  11. Larger hippocampus size in women with anorexia nervosa who exercise excessively than healthy women.

    PubMed

    Beadle, Janelle N; Paradiso, Sergio; Brumm, Michael; Voss, Michelle; Halmi, Katherine; McCormick, Laurie M

    2015-05-30

    Exercise has been shown to increase hippocampal volume in healthy older adults. Observations from animal models of diabetes and hypertension suggest that the combination of exercise and caloric restriction may exert greater neuroprotection in the hippocampus than either behavior alone. Yet, in humans, the effects of exercise and caloric restriction on the hippocampus are not known. We measured the volume of the hippocampus prior to clinical treatment in women with anorexia nervosa (AN) who were restricting calories and engaging in excessive exercise, women with AN who did not exercise excessively, and healthy women who did not engage in either behavior. Women with AN were also examined longitudinally (once weight was restored and 6 months later). In the present report, we found that women with AN engaged in caloric restriction and excessive exercising prior to clinical treatment had larger hippocampal volumes than healthy comparison women. After weight restoration, women with AN who had engaged in food restriction and excessive exercise prior to treatment had hippocampal volumes similar to that of women with AN who only engaged in caloric restriction. These results advance the field by showing for the first time that hippocampal volume may be increased by exercise alone or exercise interacting with food restriction in AN. PMID:25624068

  12. Reversible Information Flow across the Medial Temporal Lobe: The Hippocampus Links Cortical Modules during Memory Retrieval

    PubMed Central

    Cooper, Elisa; Henson, Richard N.

    2013-01-01

    A simple cue can be sufficient to elicit vivid recollection of a past episode. Theoretical models suggest that upon perceiving such a cue, disparate episodic elements held in neocortex are retrieved through hippocampal pattern completion. We tested this fundamental assumption by applying functional magnetic resonance imaging (fMRI) while objects or scenes were used to cue participants' recall of previously paired scenes or objects, respectively. We first demonstrate functional segregation within the medial temporal lobe (MTL), showing domain specificity in perirhinal and parahippocampal cortices (for object-processing vs scene-processing, respectively), but domain generality in the hippocampus (retrieval of both stimulus types). Critically, using fMRI latency analysis and dynamic causal modeling, we go on to demonstrate functional integration between these MTL regions during successful memory retrieval, with reversible signal flow from the cue region to the target region via the hippocampus. This supports the claim that the human hippocampus provides the vital associative link that integrates information held in different parts of cortex. PMID:23986252

  13. Upregulation of adenosine kinase in astrocytes in experimental and human temporal lobe epilepsy

    PubMed Central

    Aronica, Eleonora; Zurolo, Emanuele; Iyer, Anand; de Groot, Marjolein; Anink, Jasper; Carbonell, Caterina; van Vliet, Erwin A.; Baayen, Johannes C.; Boison, Detlev; Gorter, Jan A.

    2011-01-01

    Purpose Adenosine kinase (ADK) represents the key metabolic enzyme for the regulation of extracellular adenosine levels in the brain. In adult brain, ADK is primarily present in astrocytes. Several lines of experimental evidence support a critical role of ADK in different types of brain injury associated with astrogliosis, which is also a prominent morphological feature of temporal lobe epilepsy (TLE). We hypothesized that dysregulation of ADK is an ubiquitous pathological hallmark of TLE. Methods Using immunocytochemistry and western blot analysis, we investigated ADK protein expression in a rat model of TLE during epileptogenesis and the chronic epileptic phase and compared those findings with tissue resected from TLE patients with mesial temporal sclerosis (MTS). Key findings In rat control hippocampus and cortex, a low baseline expression of ADK was found with mainly nuclear localization. One week after the electrical induction of status epilepticus (SE), prominent up-regulation of ADK became evident in astrocytes with a characteristic cytoplasmic localization. This increase in ADK persisted at least for 3-4 months after SE in rats developing a progressive form of epilepsy. In line with the findings from the rat model, expression of astrocytic ADK was also found to be increased in the hippocampus and temporal cortex of TLE patients. In addition, in vitro experiments in human astrocyte cultures showed that ADK expression was increased by several pro-inflammatory molecules (interleukin-1β and LPS). Significance These results suggest that dysregulation of ADK in astrocytes is a common pathological hallmark of TLE. Moreover, in vitro data suggest the existence of an additional layer of modulatory crosstalk between the astrocyte-based adenosine cycle and inflammation. Whether this interaction also can play role in vivo needs to be further investigated. PMID:21635241

  14. M1 muscarinic receptor signaling in mouse hippocampus and cortex.

    PubMed

    Porter, Amy C; Bymaster, Frank P; DeLapp, Neil W; Yamada, Masahisa; Wess, Jürgen; Hamilton, Susan E; Nathanson, Neil M; Felder, Christian C

    2002-07-19

    The five subtypes (M1-M5) of muscarinic acetylcholine receptors signal through G(alpha)(q) or G(alpha)(i)/G(alpha)(o). M1, M3 and M5 receptors couple through G(alpha)(q) and function predominantly as postsynaptic receptors in the central nervous system. M1 and M3 receptors are localized to brain regions involved in cognition, such as hippocampus and cortex, but their relative contribution to function has been difficult to ascertain due to the lack of subtype specific ligands. A functional and genetic approach was used to identify the predominant muscarinic receptor subtype(s) mediating responses in mouse hippocampus and cortex, as well as the relative degree of spare muscarinic receptors in hippocampus. The nonselective muscarinic agonist oxotremorine-M stimulated G(alpha)(q)/11-specific GTP-gamma-35S binding in a concentration dependent manner with a Hill slope near unity in wild type mouse hippocampus and cortex. Muscarinic receptor stimulated G(alpha)(q)/11-specific GTP-gamma-35S binding was virtually abolished in both the hippocampus and cortex of M1 receptor knockout (KO) mice. In contrast, there was no loss of signaling in M3 receptor KO mice in either brain region. Muscarinic receptor reserve in wildtype mouse hippocampus was measured by Furchgott analysis after partial receptor alkylation with propylbenzylcholine mustard. Occupation of just 15% of the M1 receptors in mouse hippocampus was required for maximal efficacy of oxotremorine-M-stimulated GTP-gamma-35S binding indicating a substantial level of spare receptors. These findings support a role for the M1 receptor subtype as the primary G(alpha)(q)/11-coupled muscarinic receptor in mouse hippocampus and cortex. PMID:12106668

  15. Ketamine alters oscillatory coupling in the hippocampus

    PubMed Central

    Caixeta, Fábio V.; Cornélio, Alianda M.; Scheffer-Teixeira, Robson; Ribeiro, Sidarta; Tort, Adriano B. L.

    2013-01-01

    Recent studies show that higher order oscillatory interactions such as cross-frequency coupling are important for brain functions that are impaired in schizophrenia, including perception, attention and memory. Here we investigated the dynamics of oscillatory coupling in the hippocampus of awake rats upon NMDA receptor blockade by ketamine, a pharmacological model of schizophrenia. Ketamine (25, 50 and 75 mg/kg i.p.) increased gamma and high-frequency oscillations (HFO) in all depths of the CA1-dentate axis, while theta power changes depended on anatomical location and were independent of a transient increase of delta oscillations. Phase coherence of gamma and HFO increased across hippocampal layers. Phase-amplitude coupling between theta and fast oscillations was markedly altered in a dose-dependent manner: ketamine increased hippocampal theta-HFO coupling at all doses, while theta-gamma coupling increased at the lowest dose and was disrupted at the highest dose. Our results demonstrate that ketamine alters network interactions that underlie cognitively relevant theta-gamma coupling. PMID:23907109

  16. Role of the hippocampus and orbitofrontal cortex during the disambiguation of social cues in working memory.

    PubMed

    Ross, Robert S; LoPresti, Matthew L; Schon, Karin; Stern, Chantal E

    2013-12-01

    Human social interactions are complex behaviors requiring the concerted effort of multiple neural systems to track and monitor the individuals around us. Cognitively, adjusting our behavior on the basis of changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, the representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining the brain regions contributing to the encoding, maintenance, and retrieval of overlapping identity information during working memory using a delayed match-to-sample task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the nonoverlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and nonoverlapping conditions at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the delayed match-to-sample task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest that lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory, whereas the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest that the lateral orbitofrontal cortex and hippocampus play a role in encoding, maintaining, and retrieving social cues, especially when multiple interactions with an individual need to be disambiguated in a rapidly changing social context in order to make appropriate social responses. PMID:23640112

  17. Diabetes Alters KIF1A and KIF5B Motor Proteins in the Hippocampus

    PubMed Central

    Baptista, Filipa I.; Pinto, Maria J.; Elvas, Filipe; Almeida, Ramiro D.; Ambrósio, António F.

    2013-01-01

    Diabetes mellitus is the most common metabolic disorder in humans. Diabetic encephalopathy is characterized by cognitive and memory impairments, which have been associated with changes in the hippocampus, but the mechanisms underlying those impairments triggered by diabetes, are far from being elucidated. The disruption of axonal transport is associated with several neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the effect of diabetes (2 and 8 weeks duration) on KIF1A, KIF5B and dynein motor proteins, which are important for axonal transport, in the hippocampus. The mRNA expression of motor proteins was assessed by qRT-PCR, and also their protein levels by immunohistochemistry in hippocampal slices and immunoblotting in total extracts of hippocampus from streptozotocin-induced diabetic and age-matched control animals. Diabetes increased the expression and immunoreactivity of KIF1A and KIF5B in the hippocampus, but no alterations in dynein were detected. Since hyperglycemia is considered a major player in diabetic complications, the effect of a prolonged exposure to high glucose on motor proteins, mitochondria and synaptic proteins in hippocampal neurons was also studied, giving particular attention to changes in axons. Hippocampal cell cultures were exposed to high glucose (50 mM) or mannitol (osmotic control; 25 mM plus 25 mM glucose) for 7 days. In hippocampal cultures incubated with high glucose no changes were detected in the fluorescence intensity or number of accumulations related with mitochondria in the axons of hippocampal neurons. Nevertheless, high glucose increased the number of fluorescent accumulations of KIF1A and synaptotagmin-1 and decreased KIF5B, SNAP-25 and synaptophysin immunoreactivity specifically in axons of hippocampal neurons. These changes suggest that anterograde axonal transport mediated by these kinesins may be impaired in hippocampal neurons, which may

  18. Hippocampus and Retrosplenial Cortex Combine Path Integration Signals for Successful Navigation

    PubMed Central

    Erdem, Uğur M.; Ross, Robert S.; Brown, Thackery I.; Hasselmo, Michael E.; Stern, Chantal E.

    2013-01-01

    The current study used fMRI in humans to examine goal-directed navigation in an open field environment. We designed a task that required participants to encode survey-level spatial information and subsequently navigate to a goal location in either first person, third person, or survey perspectives. Critically, no distinguishing landmarks or goal location markers were present in the environment, thereby requiring participants to rely on path integration mechanisms for successful navigation. We focused our analysis on mechanisms related to navigation and mechanisms tracking linear distance to the goal location. Successful navigation required translation of encoded survey-level map information for orientation and implementation of a planned route to the goal. Our results demonstrate that successful first and third person navigation trials recruited the anterior hippocampus more than trials when the goal location was not successfully reached. When examining only successful trials, the retrosplenial and posterior parietal cortices were recruited for goal-directed navigation in both first person and third person perspectives. Unique to first person perspective navigation, the hippocampus was recruited to path integrate self-motion cues with location computations toward the goal location. Last, our results demonstrate that the hippocampus supports goal-directed navigation by actively tracking proximity to the goal throughout navigation. When using path integration mechanisms in first person and third person perspective navigation, the posterior hippocampus was more strongly recruited as participants approach the goal. These findings provide critical insight into the neural mechanisms by which we are able to use map-level representations of our environment to reach our navigational goals. PMID:24305826

  19. Proteomic identification of carbonylated proteins in F344 rat hippocampus after 1-bromopropane exposure

    SciTech Connect

    Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Subramanian, Kaviarasan; Mohideen, Sahabudeen Sheik; Ichihara, Gaku

    2012-08-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and humans. Previous proteomic analysis of rat hippocampus implicated alteration of protein expression in oxidative stress, suggesting that oxidative stress plays a role in 1-BP-induced neurotoxicity. To understand this role at the protein level, we exposed male F344 rats to 1-BP at 0, 400, or 1000 ppm for 8 h/day for 1 week or 4 weeks by inhalation and quantitated changes in hippocampal protein carbonyl using a protein carbonyl assay, two-dimensional gel electrophoresis (2-DE), immunoblotting, and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF/MS). Hippocampal reactive oxygen species and protein carbonyl were significantly increased, demonstrating 1-BP-associated induction of oxidative stress and protein damage. MALDI-TOF-TOF/MS identified 10 individual proteins with increased carbonyl modification (p < 0.05; fold-change ≥ 1.5). The identified proteins were involved in diverse biological processes including glycolysis, ATP production, tyrosine catabolism, GTP binding, guanine degradation, and neuronal metabolism of dopamine. Hippocampal triosephosphate isomerase (TPI) activity was significantly reduced and negatively correlated with TPI carbonylation (p < 0.001; r = 0.83). Advanced glycation end-product (AGE) levels were significantly elevated both in the hippocampus and plasma, and hippocampal AGEs correlated negatively with TPI activity (p < 0.001; r = 0.71). In conclusion, 1-BP-induced neurotoxicity in the rat hippocampus seems to involve oxidative damage of cellular proteins, decreased TPI activity, and elevated AGEs. -- Highlights: ► 1-BP increases hippocampal ROS levels and hippocampal and plasma protein carbonyls. ► 1-BP increases TPI carbonylation and decreases TPI activity in the hippocampus. ► 1-BP increases hippocampal and plasma AGE levels.

  20. Independent Neuronal Origin of Seizures and Behavioral Comorbidities in an Animal Model of a Severe Childhood Genetic Epileptic Encephalopathy.

    PubMed

    Asinof, Samuel K; Sukoff Rizzo, Stacey J; Buckley, Alexandra R; Beyer, Barbara J; Letts, Verity A; Frankel, Wayne N; Boumil, Rebecca M

    2015-06-01

    The childhood epileptic encephalopathies (EE's) are seizure disorders that broadly impact development including cognitive, sensory and motor progress with severe consequences and comorbidities. Recently, mutations in DNM1 (dynamin 1) have been implicated in two EE syndromes, Lennox-Gastaut Syndrome and Infantile Spasms. Dnm1 encodes dynamin 1, a large multimeric GTPase necessary for activity-dependent membrane recycling in neurons, including synaptic vesicle endocytosis. Dnm1Ftfl or "fitful" mice carry a spontaneous mutation in the mouse ortholog of DNM1 and recapitulate many of the disease features associated with human DNM1 patients, providing a relevant disease model of human EE's. In order to examine the cellular etiology of seizures and behavioral and neurological comorbidities, we engineered a conditional Dnm1Ftfl mouse model of DNM1 EE. Observations of Dnm1Ftfl/flox mice in combination with various neuronal subpopulation specific cre strains demonstrate unique seizure phenotypes and clear separation of major neurobehavioral comorbidities from severe seizures associated with the germline model. This demonstration of pleiotropy suggests that treating seizures per se may not prevent severe comorbidity observed in EE associated with dynamin-1 mutations, and is likely to have implications for other genetic forms of EE. PMID:26125563

  1. Dynamics of epileptic activity in a peculiar case of childhood absence epilepsy and correlation with thalamic levels of GABA

    PubMed Central

    Leal, Alberto; Vieira, José P.; Lopes, Ricardo; Nunes, Rita G.; Gonçalves, Sónia I.; Lopes da Silva, Fernando; Figueiredo, Patrícia

    2016-01-01

    Objectives Childhood absence epilepsy (CAE) is a syndrome with well-defined electroclinical features but unknown pathological basis. An increased thalamic tonic GABA inhibition has recently been discovered on animal models (Cope et al., 2009), but its relevance for human CAE is unproven. Methods We studied an 11-year-old boy, presenting the typical clinical features of CAE, but spike–wave discharges (SWD) restricted to one hemisphere. Results High-resolution EEG failed to demonstrate independent contralateral hemisphere epileptic activity. Consistently, simultaneous EEG–fMRI revealed the typical thalamic BOLD activation, associated with caudate and default mode network deactivation, but restricted to the hemisphere with SWD. Cortical BOLD activations were localized on the ipsilateral pars transverse. Magnetic resonance spectroscopy, using MEGA-PRESS, showed that the GABA/creatine ratio was 2.6 times higher in the hemisphere with SWD than in the unaffected one, reflecting a higher GABA concentration. Similar comparisons for the patient's occipital cortex and thalamus of a healthy volunteer yielded asymmetries below 25%. Significance In a clinical case of CAE with EEG and fMRI-BOLD manifestations restricted to one hemisphere, we found an associated increase in thalamic GABA concentration consistent with a role for this abnormality in human CAE. PMID:27144122

  2. Orthomolecular enhancement of human development

    NASA Technical Reports Server (NTRS)

    Pauling, L.

    1978-01-01

    The importance of molecules introduced into the human body by the way of foods is emphasized. Examples of orthomolecular therapy are given that range from the control of epileptic seizures, the therapy of mental illness, to the prevention of the common cold.

  3. Sudden death in epileptic rats exposed to nocturnal magnetic fields that simulate the shape and the intensity of sudden changes in geomagnetic activity: an experiment in response to Schnabel, Beblo and May

    NASA Astrophysics Data System (ADS)

    Persinger, M. A.; McKay, B. E.; O'Donovan, C. A.; Koren, S. A.

    2005-03-01

    To test the hypothesis that sudden unexplained death (SUD) in some epileptic patients is related to geomagnetic activity we exposed rats in which limbic epilepsy had been induced to experimentally produced magnetic fields designed to simulate sudden storm commencements (SSCs). Prior studies with rats had shown that sudden death in groups of rats in which epilepsy had been induced months earlier was associated with the occurrence of SSCs and increased geomagnetic activity during the previous night. Schnabel et al. [(2000) Neurology 54:903 908) found no relationship between SUD in human patients and geomagnetic activity. A total of 96 rats were exposed to either 500, 50, 10 40 nT or sham (less than 10 nT) magnetic fields for 6 min every hour between midnight and 0800 hours (local time) for three successive nights. The shape of the complex, amplitude-modulated magnetic fields simulated the shape and structure of an average SSC. The rats were then seized with lithium and pilocarpine and the mortality was monitored. Whereas 10% of the rats that had been exposed to the sham field died within 24 h, 60% of the rats that had been exposed to the experimental magnetic fields simulating natural geomagnetic activity died (P<.001) during this period. These results suggest that correlational analyses between SUD in epileptic patients and increased geomagnetic activity can be simulated experimentally in epileptic rats and that potential mechanisms might be testable directly.

  4. Focal seizures and epileptic spasms in a child with Down syndrome from a family with a PRRT2 mutation.

    PubMed

    Igarashi, Ayuko; Okumura, Akihisa; Shimojima, Keiko; Abe, Shinpei; Ikeno, Mitsuru; Shimizu, Toshiaki; Yamamoto, Toshiyuki

    2016-06-01

    We describe a girl with Down syndrome who experienced focal seizures and epileptic spasms during infancy. The patient was diagnosed as having trisomy 21 during the neonatal period. She had focal seizures at five months of age, which were controlled with phenobarbital. However, epileptic spasms appeared at seven months of age in association with hypsarrhythmia. Upon treatment with adrenocorticotropic hormone, her epileptic spasms disappeared. Her younger brother also had focal seizures at five months of age. His development and interictal electroencephalogram were normal. The patient's father had had infantile epilepsy and paroxysmal kinesigenic dyskinesia. We performed a mutation analysis of the PRRT2 gene and found a c.841T>C mutation in the present patient, her father, and in her younger brother. We hypothesized that the focal seizures in our patient were caused by the PRRT2 mutation, whereas the epileptic spasms were attributable to trisomy 21. PMID:26867511

  5. Complexity and multifractality of neuronal noise in mouse and human hippocampal epileptiform dynamics.

    PubMed

    Serletis, Demitre; Bardakjian, Berj L; Valiante, Taufik A; Carlen, Peter L

    2012-10-01

    Fractal methods offer an invaluable means of investigating turbulent nonlinearity in non-stationary biomedical recordings from the brain. Here, we investigate properties of complexity (i.e. the correlation dimension, maximum Lyapunov exponent, 1/f(γ) noise and approximate entropy) and multifractality in background neuronal noise-like activity underlying epileptiform transitions recorded at the intracellular and local network scales from two in vitro models: the whole-intact mouse hippocampus and lesional human hippocampal slices. Our results show evidence for reduced dynamical complexity and multifractal signal features following transition to the ictal epileptiform state. These findings suggest that pathological breakdown in multifractal complexity coincides with loss of signal variability or heterogeneity, consistent with an unhealthy ictal state that is far from the equilibrium of turbulent yet healthy fractal dynamics in the brain. Thus, it appears that background noise-like activity successfully captures complex and multifractal signal features that may, at least in part, be used to classify and identify brain state transitions in the healthy and epileptic brain, offering potential promise for therapeutic neuromodulatory strategies for afflicted patients suffering from epilepsy and other related neurological disorders. PMID:22929878

  6. Complexity and multifractality of neuronal noise in mouse and human hippocampal epileptiform dynamics

    NASA Astrophysics Data System (ADS)

    Serletis, Demitre; Bardakjian, Berj L.; Valiante, Taufik A.; Carlen, Peter L.

    2012-10-01

    Fractal methods offer an invaluable means of investigating turbulent nonlinearity in non-stationary biomedical recordings from the brain. Here, we investigate properties of complexity (i.e. the correlation dimension, maximum Lyapunov exponent, 1/fγ noise and approximate entropy) and multifractality in background neuronal noise-like activity underlying epileptiform transitions recorded at the intracellular and local network scales from two in vitro models: the whole-intact mouse hippocampus and lesional human hippocampal slices. Our results show evidence for reduced dynamical complexity and multifractal signal features following transition to the ictal epileptiform state. These findings suggest that pathological breakdown in multifractal complexity coincides with loss of signal variability or heterogeneity, consistent with an unhealthy ictal state that is far from the equilibrium of turbulent yet healthy fractal dynamics in the brain. Thus, it appears that background noise-like activity successfully captures complex and multifractal signal features that may, at least in part, be used to classify and identify brain state transitions in the healthy and epileptic brain, offering potential promise for therapeutic neuromodulatory strategies for afflicted patients suffering from epilepsy and other related neurological disorders. This paper is based on chapter 5 of Serletis (2010 PhD Dissertation Department of Physiology, Institute of Biomaterials and Biomedical Engineering, University of Toronto).

  7. Decoding Information in the Human Hippocampus: A User's Guide

    ERIC Educational Resources Information Center

    Chadwick, Martin J.; Bonnici, Heidi M.; Maguire, Eleanor A.

    2012-01-01

    Multi-voxel pattern analysis (MVPA), or "decoding", of fMRI activity has gained popularity in the neuroimaging community in recent years. MVPA differs from standard fMRI analyses by focusing on whether information relating to specific stimuli is encoded in patterns of activity across multiple voxels. If a stimulus can be predicted, or decoded,…

  8. The hippocampus and executive functions in depression

    PubMed Central

    Khan, Shahbaz Ali; Ryali, VSSR; Bhat, Pookala Shivaram; Prakash, Jyoti; Srivastava, Kalpana; Khanam, Shagufta

    2015-01-01

    Background: The relationship between depression, hippocampus (HC), and executive dysfunctions seems complex and has been the focus of research. Recent evidence indicates a possible role of HC in executive dysfunction seen in depression. No such studies on Indian population have been done. Aim: To look for changes in HC and executive functions in depression. Settings and Design: A cross-sectional analytical controlled study. Sample size 50 (controls 50). Materials and Methods: Hippocampal volume and executive dysfunction was measured using structural magnetic resonance imaging (MRI) and Wisconsin Card Sorting Test (WCST), respectively. Findings on these two parameters were compared between depressives and healthy matched controls as well as between first episode (FE) and recurrent depressives and across the severity of depression (mild, moderate, and severe). Statistical Analysis: Statistical Package for Social Sciences (SPSS) version 17 was used for analysis. Normally distributed continuous variables were analyzed with independent t-tests. Analysis of variance (ANOVA) was used for multiple comparisons. Categorical data were compared with χ2 or Fisher's exact test. Clinical correlations were conducted using Pearson correlations. Result: Depressed patients had a smaller left (Lt) hippocampal volume as well as poor performance on several measures of executive functions. Smaller hippocampal volume was found even in FE. Those who had a past burden of depressive illness had an even smaller hippocampal volume. No direct correlation was found between the HC volume and cognitive dysfunction. Conclusion: Depressive illness appears to be toxic to the HC. The relationship between HC and executive dysfunction in depression may be indirect through its functional connections. PMID:26257478

  9. Investigating the functions of subregions within anterior hippocampus

    PubMed Central

    Zeidman, Peter; Lutti, Antoine; Maguire, Eleanor A.

    2015-01-01

    Previous functional MRI (fMRI) studies have associated anterior hippocampus with imagining and recalling scenes, imagining the future, recalling autobiographical memories and visual scene perception. We have observed that this typically involves the medial rather than the lateral portion of the anterior hippocampus. Here, we investigated which specific structures of the hippocampus underpin this observation. We had participants imagine novel scenes during fMRI scanning, as well as recall previously learned scenes from two different time periods (one week and 30 min prior to scanning), with analogous single object conditions as baselines. Using an extended segmentation protocol focussing on anterior hippocampus, we first investigated which substructures of the hippocampus respond to scenes, and found both imagination and recall of scenes to be associated with activity in presubiculum/parasubiculum, a region associated with spatial representation in rodents. Next, we compared imagining novel scenes to recall from one week or 30 min before scanning. We expected a strong response to imagining novel scenes and 1-week recall, as both involve constructing scene representations from elements stored across cortex. By contrast, we expected a weaker response to 30-min recall, as representations of these scenes had already been constructed but not yet consolidated. Both imagination and 1-week recall of scenes engaged anterior hippocampal structures (anterior subiculum and uncus respectively), indicating possible roles in scene construction. By contrast, 30-min recall of scenes elicited significantly less activation of anterior hippocampus but did engage posterior CA3. Together, these results elucidate the functions of different parts of the anterior hippocampus, a key brain area about which little is definitely known. PMID:26478961

  10. Evolution of the hippocampus in reptiles and birds.

    PubMed

    Striedter, Georg F

    2016-02-15

    Although the hippocampus is structurally quite different among reptiles, birds, and mammals, its function in spatial memory is said to be highly conserved. This is surprising, given that structural differences generally reflect functional differences. Here I review this enigma in some detail, identifying several evolutionary changes in hippocampal cytoarchitecture and connectivity. I recognize a lepidosaurid pattern of hippocampal organization (in lizards, snakes, and the tuatara Sphenodon) that differs substantially from the pattern of organization observed in the turtle/archosaur lineage, which includes crocodilians and birds. Although individual subdivisions of the hippocampus are difficult to homologize between these two patterns, both lack a clear homolog of the mammalian dentate gyrus. The strictly trilaminar organization of the ancestral amniote hippocampus was gradually lost in the lineage leading to birds, and birds expanded the system of intrahippocampal axon collaterals, relative to turtles and lizards. These expanded collateral axon branches resemble the extensive collaterals in CA3 of the mammalian hippocampus but probably evolved independently of them. Additional examples of convergent evolution between birds and mammals are the loss of direct inputs to the hippocampus from the primary olfactory cortex and the general expansion of telencephalic regions that communicate reciprocally with the hippocampus. Given this structural convergence, it seems likely that some similarities in the function of the hippocampus between birds and mammals, notably its role in the ability to remember many different locations without extensive training, likewise evolved convergently. The currently available data do not allow for a strong test of this hypothesis, but the hypothesis itself suggests some promising new research directions. PMID:25982694

  11. The involvement of neuronal nitric oxide synthase in the anti-epileptic action of curcumin on pentylenetetrazol-kindled rats.

    PubMed

    Zhu, Wenting; Su, Jing; Liu, Jing; Jiang, Changbin

    2015-01-01

    In this study, it was investigated whether a NO signaling pathway is involved in the anti-epileptic effect of curcumin on pentylenetetrazol (PTZ)-kindled rats. PTZ-kindled rats received different doses of curcumin that were administered intraperitoneally for 24 days. Either a non-selective inhibitor of nitric oxide synthase (NOS) (N-nitro-L-arginine methyl ester (L-NAME)), a selective inhibitor of neuronal NOS (7-Nitroindazole (7-NI)), a selective inhibitor of inducible NOS (aminoguanidine (AG)), or a NO precursor (L-arginine (L-ARG)) was administered chronically to evaluate the role of NO in curcumin's anti-seizure effect. A chronic administration of curcumin (200 mg/kg) was most effective for decreasing the mean frequency of epileptiform discharge. Furthermore, a pretreatment with L-NAME or 7-NI augmented the anti-epileptic effect of curcumin. In contrast, AG failed to significantly alter the anti-epileptic effect of curcumin. A pretreatment with L-ARG temporally reversed the anti-epileptic effect of curcumin in the early stage, but in the late stage, it potentiated curcumin's anti-epileptic effect. These findings suggest that the L-arginine-nitric oxide pathway may be involved in the anti-epileptic properties of curcumin, and that the role of nNOS (and not iNOS) is prominent in this neuroprotective feature. PMID:26406082

  12. Does Early Environmental Complexity Influence Tyrosine Hydroxylase in the Chicken Hippocampus and “Prefrontal” Caudolateral Nidopallium?

    PubMed Central

    Tahamtani, Fernanda M.; Nordgreen, Janicke; Brantsæter, Margrethe; Østby, Gunn C.; Nordquist, Rebecca E.; Janczak, Andrew M.

    2016-01-01

    In adult chickens, the housing system influences hippocampal morphology and neurochemistry. However, no work has been done investigating the effects of the early life environment on chicken brain development. In the present study, we reared 67 commercial laying hens (Gallus gallus domesticus) in two environments that differed in the degree of complexity (aviary or cage system). These two groups were further divided into two age groups. At 20 weeks of age, 18 aviary-reared birds and 15 cage-reared birds were humanely euthanized and their brains dissected. At 24 weeks of age, a further 16 brains from aviary-reared birds and 18 brains from cage-reared birds were collected. These brains were prepared for immunohistochemical detection of tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of dopamine, in the hippocampus and the caudolateral nidopallium (NCL). There were no differences between the treatment groups in TH staining intensity in the hippocampus or the NCL. In the medial hippocampus, the right hemisphere had higher TH staining intensity compared to the left hemisphere. The opposite was true for the NCL, with the left hemisphere being more strongly stained compared to the right hemisphere. The present study supports the notion that the hippocampus is functionally lateralized, and our findings add to the body of knowledge on adult neural plasticity of the avian brain. PMID:26904550

  13. Resting state functional connectivity of the hippocampus along the anterior-posterior axis and its association with glutamatergic metabolism.

    PubMed

    Wagner, Gerd; Gussew, Alexander; Köhler, Stefanie; de la Cruz, Feliberto; Smesny, Stefan; Reichenbach, Jürgen R; Bär, Karl-Jürgen

    2016-08-01

    Animal and human studies suggest differing anatomical and functional connectivity patterns of the anterior and posterior hippocampus. The biochemical underpinnings of the hippocampal resting state connectivity along this anterior-posterior axis remain unclear. We investigated twenty-five healthy male subjects in a multimodal study. We aimed to examine the relationship between resting state functional connectivity (RSFC) of the left and right hippocampus separated along the anterior-posterior axis and the corresponding glutamatergic function assessed by proton magnetic resonance spectroscopy ((1)H-MRS) of the glutamate-glutamine (Glx) complex. We observed a clear functional differentiation of the hippocampal RSFC along this axis. Moreover, a highly significant correlation was observed between the concentration of Glx in the right anterior hippocampus and its corresponding functional connectivity, but not with the amplitude of local low frequency fluctuations. Lower Glx levels were associated with a higher functional connectivity to the medial prefrontal cortex, perigenual anterior cingulate cortex (pACC) and the left ventrolateral prefrontal cortex (VLPFC). In addition, the Glx concentration in the posterior hippocampus predicted the verbal memory performance, i.e., the degree of retroactive interference. The present findings demonstrate for the first time a modulation of the anterior hippocampal RSFC by Glx concentration. PMID:27182810

  14. Differential effect of lithium on cell number in hippocampus and prefrontal cortex in adult mice: a stereological study

    PubMed Central

    Rajkowska, G.; Clarke, G.; Mahajan, G.; Licht, C.M.M.; van de Werd, H.J.J. M.; Yuan, P.; Stockmeier, C.A.; Manji, H.K.; Uylings, H.B.M.

    2015-01-01

    Objectives Neuroimaging studies note lithium-related increases in the volume of gray matter in prefrontal cortex (PFC) and hippocampus. Postmortem human studies report alterations in neuronal and glial cell density and size in the PFC of lithium-treated subjects. Rodents treated with lithium exhibit cell proliferation in the dentate gyrus (DG) of the hippocampus. However, it is not known whether hippocampal and PFC volume are also increased in these animals or whether cell number in the PFC is altered. Methods Using stereological methods, this study estimated the total number of neurons, glia and the packing density of astrocytes in the DG and PFC of normal adult mice treated with lithium and evaluated the total volume of these regions and the entire neocortex. Results Lithium treatment increased the total number of neurons and glia in the DG (25% and 21%, respectively) and the density of astrocytes but did not alter the total number in the PFC. However, the volume of the hippocampus and its subfields, the PFC and its subareas, and the entire neocortex were not altered by lithium. Conclusions Both neuronal and glial cells accounted for lithium-induced cell proliferation in the DG. That the number of neurons and glia were unchanged in the PFC is consistent with the view that this region is not a neurogenic zone. Further studies are required to clarify the impact of lithium treatment on the PFC under pathological conditions and to investigate the dissociation between increased cell proliferation and unchanged volume in the hippocampus. PMID:26842627

  15. Ethical Dilemmas in Pediatric and Adolescent Psychogenic Non-Epileptic Seizures

    PubMed Central

    Cole, Cristie M.; Falcone, Tatiana; Caplan, Rochelle; Timmons-Mitchell, Jane; Jares, Kristine; Ford, Paul J.

    2014-01-01

    To date only a very narrow window of ethical dilemmas in psychogenic non-epileptic seizures (PNES) have been explored. Numerous distinct ethical dilemmas arise in diagnosing and treating pediatric and adolescent patients with PNES. Important ethical values at stake include trust, transparency, confidentiality, professionalism, autonomy of all stakeholders and justice. In order to further elucidate the ethical challenges in caring for this population, an ethical analysis of the special challenges faced in four specific domains is undertaken: (1) conducting and communicating a diagnosis of PNES; (2) advising patients about full transparency and disclosure to community including patients’ peers; (3) responding to requests to continue anti-epileptic drugs; and (4) managing challenges arising from school policy and procedure. An analysis of these ethical issues is essential for the advancement of best care practices that promote the overall well-being of patients and their families. PMID:25022823

  16. Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain.

    PubMed

    Bonansco, Christian; Fuenzalida, Marco

    2016-01-01

    Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I) balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks. PMID:27006834

  17. Posterior Reversible Encephalopathy Syndrome with Bilateral Independent Epileptic Foci Precipitated By Guillain-Barrè Syndrome.

    PubMed

    Rossi, Rosario; Saddi, Maria Valeria; Mela, Alessandro; Ticca, Anna

    2016-01-01

    We report the case of a 56-year-old woman who developed status epilepticus (SE) related to independent occipital foci as clinical manifestation of posterior reversible encephalopathy syndrome (PRES) in the background of Guillain-Barrè syndrome (GBS). SE resulted from a series of focal seizures clinically characterized by left- and rightward deviations of the head and consequent oculoclonic movements. Electroencephalography recorded independent seizure activity in both occipital regions with alternate involvement of the two cerebral hemispheres. The epileptic foci corresponded topographically to parenchymal abnormalities of PRES in the occipital lobes. The manifestation of bilateral, independent occipital seizures with alternate deviations of the head and oculoclonic movements, previously not reported in patients with PRES, highlights the acute epileptogenicity of the cerebral lesions in this syndrome. Despite the variable clinical expression of seizures due to occipital damage in PRES, the development of independent seizure activity in both occipital lobes might represent a distinctive epileptic phenomenon of this encephalopathy. PMID:27403359

  18. Behavioural epileptic seizures: a clinical and intracranial EEG study in 8 children with frontal lobe epilepsy.

    PubMed

    Fohlen, M; Bulteau, C; Jalin, C; Jambaque, I; Delalande, O

    2004-12-01

    We report on eight children who underwent prolonged invasive video-EEG recording (IC-EEG) for intractable frontal lobe epilepsy and whose seizures consisted of behaviour changes. Seizures were recorded on a BMSI computer with 128 channels connected to the Gotman software of a stellate system; their identification was made both clinically and by automatic detection of paroxysmal electrical events. Behavioural epileptic seizures (BES) consisted of various clinical signs comprising mood change, sudden agitation, unexpected quietness, and subtle change of awareness or awakening. In 2 patients, seizures consisted in repetitive movements that we referred to as epileptic stereotypes. BES came from the prefrontal areas of the brain. Most of them were overlooked or misdiagnosed as behavioural manifestations, especially in children with mental deficiency and autistic features. Given the improvement of behaviour and mental functions following surgery, we assume that BES may contribute to generate mental and behavioural dysfunction. PMID:15627941

  19. Posterior Reversible Encephalopathy Syndrome with Bilateral Independent Epileptic Foci Precipitated By Guillain-Barrè Syndrome

    PubMed Central

    Rossi, Rosario; Saddi, Maria Valeria; Mela, Alessandro; Ticca, Anna

    2016-01-01

    We report the case of a 56-year-old woman who developed status epilepticus (SE) related to independent occipital foci as clinical manifestation of posterior reversible encephalopathy syndrome (PRES) in the background of Guillain-Barrè syndrome (GBS). SE resulted from a series of focal seizures clinically characterized by left- and rightward deviations of the head and consequent oculoclonic movements. Electroencephalography recorded independent seizure activity in both occipital regions with alternate involvement of the two cerebral hemispheres. The epileptic foci corresponded topographically to parenchymal abnormalities of PRES in the occipital lobes. The manifestation of bilateral, independent occipital seizures with alternate deviations of the head and oculoclonic movements, previously not reported in patients with PRES, highlights the acute epileptogenicity of the cerebral lesions in this syndrome. Despite the variable clinical expression of seizures due to occipital damage in PRES, the development of independent seizure activity in both occipital lobes might represent a distinctive epileptic phenomenon of this encephalopathy. PMID:27403359

  20. Subclinical tonic-clonic epileptic seizure detected by an implantable loop recorder.

    PubMed

    Kohno, Ritsuko; Abe, Haruhiko; Akamatsu, Naoki; Tamura, Masahito; Takeuchi, Masaaki; Otsuji, Yutaka; Benditt, David G

    2013-01-01

    A 73-year old man received an implantable loop recorder (ILR) for the evaluation of transient loss of consciousness (TLOC) spells. His medical history was without any epileptic convulsions or automatism. ILR recording during a spontaneous episode revealed the presence of a regular, narrow QRS complex tachycardia associated with low-amplitude, high-frequency, continuous or discontinuous artifacts, consistent with myopotentials. During the event, the regular, low-amplitude continuous signals gradually became discontinuous, with a prolongation of the inter-signal cycle length, until their disappearance after manual activation of the ILR. The patient was diagnosed as experiencing subclinical tonic-clonic epileptic seizures. Antiepileptic drug treatment was initiated, and the patient has remained free of TLOC symptoms during 13 months follow-up. PMID:24097218

  1. Real-time Detection of Precursors to Epileptic Seizures: Non-Linear Analysis of System Dynamics

    PubMed Central

    Nesaei, Sahar; Sharafat, Ahmad R.

    2014-01-01

    We propose a novel approach for detecting precursors to epileptic seizures in intracranial electroencephalograms (iEEG), which is based on the analysis of system dynamics. In the proposed scheme, the largest Lyapunov exponent of the discrete wavelet packet transform (DWPT) of the segmented EEG signals is considered as the discriminating features. Such features are processed by a support vector machine (SVM) classifier to identify whether the corresponding segment of the EEG signal contains a precursor to an epileptic seizure. When consecutive EEG segments contain such precursors, a decision is made that a precursor is in fact detected. The proposed scheme is applied to the Freiburg dataset, and the results show that seizure precursors are detected in a time frame that unlike other existing schemes is very much convenient to patients, with sensitivity of 100% and negligible false positive detection rates. PMID:24761374

  2. Late-onset epileptic spasms in a female patient with a CASK mutation.

    PubMed

    Nakajiri, Tomoshi; Kobayashi, Katsuhiro; Okamoto, Nobuhiko; Oka, Makio; Miya, Fuyuki; Kosaki, Kenjiro; Yoshinaga, Harumi

    2015-10-01

    We report a female patient with late-onset epileptic spasms (ESs) of a rare form, distinct from those seen in typical West syndrome, in association with a heterozygous frameshift CASK mutation (c.1896dupC (p.C633fs(∗)2)). She has a phenotype of microcephaly with pontine and cerebellar hypoplasia (MICPCH), and has had intractable ESs in clusters since 3 years 8 months of age with multifocal, particularly bifrontal, epileptic discharges in electroencephalogram. The available literature on patients with both ESs and CASK mutations has been reviewed, revealing that four of the five female children, including the present girl, had late-onset ESs, in contrast to the four males, who tended toward early-onset ESs. PMID:25765806

  3. Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain

    PubMed Central

    Bonansco, Christian; Fuenzalida, Marco

    2016-01-01

    Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I) balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks. PMID:27006834

  4. Predictability of epileptic seizures: a comparative study using Lyapunov exponent and entropy based measures.

    PubMed

    Sabesan, Shivkumar; Narayanan, K; Prasad, Awadhesh; Spanias, A; Sackellares, J C; Iasemidis, L D

    2003-01-01

    In this paper, a comparative study involving measures from the theory of chaos, namely the short-term largest Lyapunov exponent, Shannon and Kullback-Leibler entropies from information theory, has been carried out in terms of their predictability of temporal lobe epileptic seizures. These three measures are estimated from electroencephalographic (EEG) recordings with sub-dural and in-depth electrodes from various brain locations in patients with temporal lobe epilepsy. Techniques from optimization theory are applied to select optimal sets of electrodes whose dynamics is then followed over time. Results from analysis of multiple seizures in two epileptic patients with these measures are presented and compared in terms of their ability to identify pre-ictal dynamical entrainment well ahead of seizure onset time. PMID:12724881

  5. [A study of 95 families having at least two epileptic children (author's transl)].

    PubMed

    Sternberg, B; Patry, G

    1979-01-01

    This report concerns a study of 95 families in which at least two of the children had epilepsy (a total of 210 cases). A total of 45 p. 100 of the patients were from 60 p. 100 of the families and had an intellectual level below the average, and 32 p. 100 of them had an IQ below 70. The family history was the same whether the children were mentally deficient or not. There was no family history of mental deficiency in those families where the epileptic children had a normal IQ but there was a positive family history in 25 p. 100 of families having at least one mentally deficient and epileptic child. The persistence of seizures after 5 years of treatment is seen much more frequently in mentally deficient children than in those with normal intelligence. Finally, the position of the child within the family has no influence and epilepsy may be found in any of the children. PMID:115068

  6. Constructing realistic engrams: poststimulus activity of hippocampus and dorsal striatum predicts subsequent episodic memory.

    PubMed

    Ben-Yakov, Aya; Dudai, Yadin

    2011-06-15

    Encoding of real-life episodic memory commonly involves integration of information as the episode unfolds. Offline processing immediately following event offset is expected to play a role in encoding the episode into memory. In this study, we examined whether distinct human brain activity time-locked to the offset of short narrative audiovisual episodes could predict subsequent memory for the gist of the episodes. We found that a set of brain regions, most prominently the bilateral hippocampus and the bilateral caudate nucleus, exhibit memory-predictive activity time-locked to the stimulus offset. We propose that offline activity in these regions reflects registration to memory of integrated episodes. PMID:21677186

  7. A Review of Adversity, The Amygdala and the Hippocampus: A Consideration of Developmental Timing

    PubMed Central

    Tottenham, Nim; Sheridan, Margaret A.

    2009-01-01

    A review of the human developmental neuroimaging literature that investigates outcomes following exposure to psychosocial adversity is presented with a focus on two subcortical structures – the hippocampus and the amygdala. Throughout this review, we discuss how a consideration of developmental timing of adverse experiences and age at measurement might provide insight into the seemingly discrepant findings across studies. We use findings from animal studies to suggest some mechanisms through which timing of experiences may result in differences across time and studies. The literature suggests that early life may be a time of heightened susceptibility to environmental stressors, but that expression of these effects will vary by age at measurement. PMID:20161700

  8. Alterations in miRNA Levels in the Dentate Gyrus in Epileptic Rats

    PubMed Central

    Bot, Anna Maria; Dębski, Konrad Józef; Lukasiuk, Katarzyna

    2013-01-01

    The aim of this study was to characterize changes in miRNA expression in the epileptic dentate gyrus. Status epilepticus evoked by amygdala stimulation was used to induce epilepsy in rats. The dentate gyri were isolated at 7 d, 14 d, 30 d and 90 d after stimulation (n=5). Sham-operated time-matched controls were prepared for each time point (n=5). The miRNA expression was evaluated using Exiqon microarrays. Additionally, mRNA from the same animals was profiled using Affymetrix microarrays. We detected miRNA expression signatures that differentiate between control and epileptic animals. Significant changes in miRNA expression between stimulated and sham operated animals were observed at 7 and 30 d following stimulation. Moreover, we found that there are ensembles of miRNAs that change expression levels over time. Analysis of the mRNA expression from the same animals revealed that the expression of several mRNAs that are potential targets for miRNA with altered expression level is regulated in the expected direction. The functional characterization of miRNAs and their potential mRNA targets indicate that miRNA can participate in several molecular events that occur in epileptic tissue, including immune response and neuronal plasticity. This is the first report on changes in the expression of miRNA and the potential functional impact of these changes in the dentate gyrus of epileptic animals. Complex changes in the expression of miRNAs suggest an important role for miRNA in the molecular mechanisms of epilepsy. PMID:24146813

  9. Apparatus and method for epileptic seizure detection using non-linear techniques

    DOEpatents

    Hively, L.M.; Clapp, N.E.; Daw, C.S.; Lawkins, W.F.

    1998-04-28

    Methods and apparatus are disclosed for automatically detecting epileptic seizures by monitoring and analyzing brain wave (EEG or MEG) signals. Steps include: acquiring the brain wave data from the patient; digitizing the data; obtaining nonlinear measures of the data via chaotic time series analysis; obtaining time serial trends in the nonlinear measures; determining that one or more trends in the nonlinear measures indicate a seizure, and providing notification of seizure occurrence. 76 figs.

  10. Detection of epileptic activity in fMRI without recording the EEG

    PubMed Central

    Lopes, R.; Lina, J.M.; Fahoum, F.; Gotman, J.

    2013-01-01

    EEG–fMRI localizes epileptic foci by detecting cerebral hemodynamic changes that are correlated to epileptic events visible in EEG. However, scalp EEG is insensitive to activity restricted to deep structures and recording the EEG in the scanner is complex and results in major artifacts that are difficult to remove. This study presents a new framework for identifying the BOLD manifestations of epileptic discharges without having to record the EEG. The first stage is based on the detection of epileptic events for each voxel by sparse representation in the wavelet domain. The second stage is to gather voxels according to proximity in time and space of detected activities. This technique was evaluated on data generated by superposing artificial responses at different locations and responses amplitude in the brain for 6 control subject runs. The method was able to detect effectively and consistently for responses amplitude of at least 1% above baseline. 46 runs from 15 patients with focal epilepsy were investigated. The results demonstrate that the method detected at least one concordant event in 37/41 runs. The maps of activation obtained from our method were more similar to those obtained by EEG–fMRI than to those obtained by the other method used in this context, 2D-Temporal Cluster Analysis. For 5 runs without event read on scalp EEG, 3 runs showed an activation concordant with the patient’s diagnostic. It may therefore be possible, at least when spikes are infrequent, to detect their BOLD manifestations without having to record the EEG. PMID:22306797

  11. Frog Appliance- An Innovative Treatment Option for the Replacement of Missing Teeth in An Epileptic Child

    PubMed Central

    Goyal, Anita; Reddy, Hanumanth; Sajjnar, Arun B; Jain, Sonal

    2015-01-01

    Epilepsy is a chronic neurological disease which may result in various oro-facial injuries among which fracture of crown and avulsion of tooth are commonly reported. Challenges come in growing epileptic children where fixed prosthesis could not be delivered and it demands a fixed semi-permanent prosthesis that needs strength along with esthetics. The present paper reports an innovative appliance which has fulfilled fore mentioned criteria; with the appliance named-frog appliance. PMID:26155578

  12. Frog Appliance- An Innovative Treatment Option for the Replacement of Missing Teeth in An Epileptic Child.

    PubMed

    Shetty, Raghavendra M; Goyal, Anita; Reddy, Hanumanth; Sajjnar, Arun B; Jain, Sonal

    2015-05-01

    Epilepsy is a chronic neurological disease which may result in various oro-facial injuries among which fracture of crown and avulsion of tooth are commonly reported. Challenges come in growing epileptic children where fixed prosthesis could not be delivered and it demands a fixed semi-permanent prosthesis that needs strength along with esthetics. The present paper reports an innovative appliance which has fulfilled fore mentioned criteria; with the appliance named-frog appliance. PMID:26155578

  13. Generalized synchronization in the complex network: theory and applications to epileptic brain

    NASA Astrophysics Data System (ADS)

    Moskalenko, Olga I.; Pivovarov, Anatoly A.; Pavlov, Alexey N.; Koronovskii, Alexey A.; Khramova, Marina V.; Hramov, Alexander E.

    2016-04-01

    Generalized synchronization in complex networks with chaotic dynamical systems being in their nodes has been studied. The synchronous regime is shown to be detected by the sign-change of the second positive Lyapunov exponent of the network or by the nearest neighbor method. The same method is shown to be applied for the detection of the synchronous regime between the different fields of epileptic brain.

  14. Burn injury in epileptic patients: an experience in a tertiary institute.

    PubMed

    Akhtar, M S; Ahmad, I; Khan, A H; Fahud Khurram, M; Haq, A

    2014-09-30

    The objective of this study was to evaluate the incidence, types and severity of burn injuries, including sites involved, morbidities, operative procedures, and their outcomes, to prevent or reduce the frequency and morbidity of such injuries in epileptic patients. This retrospective study was conducted at our centre between February 2008 and January 2012. The study included 54 patients who sustained burn injuries due to epileptic seizures, accounting for 1.3% of all burn admissions. All patients, irrespective of the severity of their injuries, were admitted to our centre, assessed, treated and educated regarding specific preventive measures. All study data were evaluated from patient medical records. Causes of burn injury were as follows: scald burns (30), contact with hot surfaces (12), electrical burns in the bathroom (6), and flame burns (6). Second degree burns were the most common (18 out of 54 patients) and third degree burns were the least common. Upper limb and trunk were the most common sites involved (36 out of 54 patients). Thirty patients required surgical intervention whereas the remainder was conservatively managed. Most of the injuries occurred in the age group between 30-37 years. Injuries occurred predominantly in females [42 females, 12 males; F:M=3.5:1]. The study revealed that patients with epilepsy should be categorized as a high risk group considering the sudden and unpredictable attack of epileptic seizures leading to loss of consciousness and accidental burn injuries. Early surgical intervention and targeting of all epileptic patients for education and instituting the specific preventive measures gives good outcomes. PMID:26170789

  15. Apparatus and method for epileptic seizure detection using non-linear techniques

    DOEpatents

    Hively, Lee M.; Clapp, Ned E.; Daw, C. Stuart; Lawkins, William F.

    1998-01-01

    Methods and apparatus for automatically detecting epileptic seizures by monitoring and analyzing brain wave (EEG or MEG) signals. Steps include: acquiring the brain wave data from the patient; digitizing the data; obtaining nonlinear measures of the data via chaotic time series analysis; obtaining time serial trends in the nonlinear measures; determining that one or more trends in the nonlinear measures indicate a seizure, and providing notification of seizure occurrence.

  16. Sleep-related epileptic behaviors and non-REM-related parasomnias: Insights from stereo-EEG.

    PubMed

    Gibbs, Steve A; Proserpio, Paola; Terzaghi, Michele; Pigorini, Andrea; Sarasso, Simone; Lo Russo, Giorgio; Tassi, Laura; Nobili, Lino

    2016-02-01

    During the last decade, many clinical and pathophysiological aspects of sleep-related epileptic and non-epileptic paroxysmal behaviors have been clarified. Advances have been achieved in part through the use of intracerebral recording methods such as stereo-electroencephalography (S-EEG), which has allowed a unique "in vivo" neurophysiological insight into focal epilepsy. Using S-EEG, the local features of physiological and pathological EEG activity in different cortical and subcortical structures have been better defined during the entire sleep-wake spectrum. For example, S-EEG has contributed to clarify the semiology of sleep-related seizures as well as highlight the specific epileptogenic networks involved during ictal activity. Moreover, intracerebral EEG recordings derived from patients with epilepsy have been valuable to study sleep physiology and specific sleep disorders. The occasional co-occurrence of NREM-related parasomnias in epileptic patients undergoing S-EEG investigation has permitted the recordings of such events, highlighting the presence of local electrophysiological dissociated states and clarifying the underlying pathophysiological substrate of such NREM sleep disorders. Based on these recent advances, the authors review and summarize the current and relevant S-EEG literature on sleep-related hypermotor epilepsies and NREM-related parasomnias. Finally, novel data and future research hypothesis will be discussed. PMID:26164370

  17. The Classical Pathways of Occipital Lobe Epileptic Propagation Revised in the Light of White Matter Dissection

    PubMed Central

    Latini, Francesco; Hjortberg, Mats; Aldskogius, Håkan; Ryttlefors, Mats

    2015-01-01

    The clinical evidences of variable epileptic propagation in occipital lobe epilepsy (OLE) have been demonstrated by several studies. However the exact localization of the epileptic focus sometimes represents a problem because of the rapid propagation to frontal, parietal, or temporal regions. Each white matter pathway close to the supposed initial focus can lead the propagation towards a specific direction, explaining the variable semiology of these rare epilepsy syndromes. Some new insights in occipital white matter anatomy are herein described by means of white matter dissection and compared to the classical epileptic patterns, mostly based on the central position of the primary visual cortex. The dissections showed a complex white matter architecture composed by vertical and longitudinal bundles, which are closely interconnected and segregated and are able to support specific high order functions with parallel bidirectional propagation of the electric signal. The same sublobar lesions may hyperactivate different white matter bundles reemphasizing the importance of the ictal semiology as a specific clinical demonstration of the subcortical networks recruited. Merging semiology, white matter anatomy, and electrophysiology may lead us to a better understanding of these complex syndromes and tailored therapeutic options based on individual white matter connectivity. PMID:26063964

  18. Fast monitoring of epileptic seizures using recurrence time statistics of electroencephalography

    PubMed Central

    Gao, Jianbo; Hu, Jing

    2013-01-01

    Epilepsy is a relatively common brain disorder which may be very debilitating. Currently, determination of epileptic seizures often involves tedious, time-consuming visual inspection of electroencephalography (EEG) data by medical experts. To better monitor seizures and make medications more effective, we propose a recurrence time based approach to characterize brain electrical activity. Recurrence times have a number of distinguished properties that make it very effective for forewarning epileptic seizures as well as studying propagation of seizures: (1) recurrence times amount to periods of periodic signals, (2) recurrence times are closely related to information dimension, Lyapunov exponent, and Kolmogorov entropy of chaotic signals, (3) recurrence times embody Shannon and Renyi entropies of random fields, and (4) recurrence times can readily detect bifurcation-like transitions in dynamical systems. In particular, property (4) dictates that unlike many other non-linear methods, recurrence time method does not require the EEG data be chaotic and/or stationary. Moreover, the method only contains a few parameters that are largely signal-independent, and hence, is very easy to use. The method is also very fast—it is fast enough to on-line process multi-channel EEG data with a typical PC. Therefore, it has the potential to be an excellent candidate for real-time monitoring of epileptic seizures in a clinical setting. PMID:24137126

  19. Fast monitoring of epileptic seizures using recurrence time statistics of electroencephalography.

    PubMed

    Gao, Jianbo; Hu, Jing

    2013-01-01

    Epilepsy is a relatively common brain disorder which may be very debilitating. Currently, determination of epileptic seizures often involves tedious, time-consuming visual inspection of electroencephalography (EEG) data by medical experts. To better monitor seizures and make medications more effective, we propose a recurrence time based approach to characterize brain electrical activity. Recurrence times have a number of distinguished properties that make it very effective for forewarning epileptic seizures as well as studying propagation of seizures: (1) recurrence times amount to periods of periodic signals, (2) recurrence times are closely related to information dimension, Lyapunov exponent, and Kolmogorov entropy of chaotic signals, (3) recurrence times embody Shannon and Renyi entropies of random fields, and (4) recurrence times can readily detect bifurcation-like transitions in dynamical systems. In particular, property (4) dictates that unlike many other non-linear methods, recurrence time method does not require the EEG data be chaotic and/or stationary. Moreover, the method only contains a few parameters that are largely signal-independent, and hence, is very easy to use. The method is also very fast-it is fast enough to on-line process multi-channel EEG data with a typical PC. Therefore, it has the potential to be an excellent candidate for real-time monitoring of epileptic seizures in a clinical setting. PMID:24137126

  20. Ictal but Not Interictal Epileptic Discharges Activate Astrocyte Endfeet and Elicit Cerebral Arteriole Responses

    PubMed Central

    Gómez-Gonzalo, Marta; Losi, Gabriele; Brondi, Marco; Uva, Laura; Sato, Sebastian Sulis; de Curtis, Marco; Ratto, Gian Michele; Carmignoto, Giorgio

    2011-01-01

    Activation of astrocytes by neuronal signals plays a central role in the control of neuronal activity-dependent blood flow changes in the normal brain. The cellular pathways that mediate neurovascular coupling in the epileptic brain remain, however, poorly defined. In a cortical slice model of epilepsy, we found that the ictal, seizure-like discharge, and only to a minor extent the interictal discharge, evokes both a Ca2+ increase in astrocyte endfeet and a vasomotor response. We also observed that rapid ictal discharge-induced arteriole responses were regularly preceded by Ca2+ elevations in endfeet and were abolished by pharmacological inhibition of Ca2+ signals in these astrocyte processes. Under these latter conditions, arterioles exhibited after the ictal discharge only slowly developing vasodilations. The poor efficacy of interictal discharges, compared with ictal discharges, to activate endfeet was confirmed also in the intact in vitro isolated guinea pig brain. Although the possibility of a direct contribution of neurons, in particular in the late response of cerebral blood vessels to epileptic discharges, should be taken into account, our study supports the view that astrocytes are central for neurovascular coupling also in the epileptic brain. The massive endfeet Ca2+ elevations evoked by ictal discharges and the poor response to interictal events represent new information potentially relevant to interpret data from diagnostic brain imaging techniques, such as functional magnetic resonance, utilized in the clinic to localize neural activity and to optimize neurosurgery of untreatable epilepsies. PMID:21747758

  1. Brain Graph Topology Changes Associated with Anti-Epileptic Drug Use

    PubMed Central

    Levin, Harvey S.; Chiang, Sharon

    2015-01-01

    Abstract Neuroimaging studies of functional connectivity using graph theory have furthered our understanding of the network structure in temporal lobe epilepsy (TLE). Brain network effects of anti-epileptic drugs could influence such studies, but have not been systematically studied. Resting-state functional MRI was analyzed in 25 patients with TLE using graph theory analysis. Patients were divided into two groups based on anti-epileptic medication use: those taking carbamazepine/oxcarbazepine (CBZ/OXC) (n=9) and those not taking CBZ/OXC (n=16) as a part of their medication regimen. The following graph topology metrics were analyzed: global efficiency, betweenness centrality (BC), clustering coefficient, and small-world index. Multiple linear regression was used to examine the association of CBZ/OXC with graph topology. The two groups did not differ from each other based on epilepsy characteristics. Use of CBZ/OXC was associated with a lower BC. Longer epilepsy duration was also associated with a lower BC. These findings can inform graph theory-based studies in patients with TLE. The changes observed are discussed in relation to the anti-epileptic mechanism of action and adverse effects of CBZ/OXC. PMID:25492633

  2. Reducing the Cost of the Diagnostic Odyssey in Early Onset Epileptic Encephalopathies

    PubMed Central

    Mansilla, M. Adela; Campbell, Colleen A.

    2016-01-01

    Whole exome sequencing (WES) has revolutionized the way we think about and diagnose epileptic encephalopathies. Multiple recent review articles discuss the benefits of WES and suggest various algorithms to follow for determining the etiology of epileptic encephalopathies. Incorporation of WES in these algorithms is leading to the discovery of new genetic diagnoses of early onset epileptic encephalopathies (EOEEs) at a rapid rate; however, WES is not yet a universally utilized diagnostic tool. Clinical WES may be underutilized due to provider discomfort in ordering the test or perceived costliness. At our hospital WES is not routinely performed for patients with EOEE due to limited insurance reimbursement. In fact for any patient with noncommercial insurance (Medicaid) the institution does not allow sending out WES as this is not “established”/“proven to be highly useful and cost effective”/“approved test” in patients with epilepsy. Recently, we performed WES on four patients from three families and identified novel mutations in known epilepsy genes in all four cases. These patients had State Medicaid as their insurance carrier and were followed up for several years for EOEE while being worked up using the traditional/approved testing methods. Following a recently proposed diagnostic pathway, we analyzed the cost savings (US dollars) that could be accrued if WES was performed earlier in the diagnostic odyssey. This is the first publication that addresses the dollar cost of traditional testing in EOEE as performed in these four cases versus WES and the potential cost savings. PMID:27243033

  3. Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants

    PubMed Central

    Talat, Mohamed A.; Ahmed, Anwar; Mohammed, Lamia

    2015-01-01

    Objective: To evaluate the serum levels of zinc and copper in epileptic children during the long-term treatment of anticonvulsant drugs and correlate this with healthy subjects. Methods: A hospital-based group matched case-control study was conducted in the Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt between November 2013 and October 2014. Ninety patients aged 7.1±3.6 years were diagnosed with epilepsy by a neurologist. The control group was selected from healthy individuals and matched to the case group. Serum zinc and copper were measured by the calorimetric method using a colorimetric method kit. Results: The mean zinc level was 60.1±22.6 ug/dl in the cases, and 102.1±18 ug/dl in the controls (p<0.001). The mean copper level was 180.1±32.4 ug/dl in cases compared with 114.5±18.5 ug/dl in controls (p<0.001). Conclusion: Serum zinc levels in epileptic children under drug treatment are lower compared with healthy children. Also, serum copper levels in these patients are significantly higher than in healthy people. No significant difference in the levels of serum copper and zinc was observed in using one drug or multiple drugs in the treatment of epileptic patients. PMID:26492112

  4. Early-onset epileptic encephalopathies and the diagnostic approach to underlying causes

    PubMed Central

    Hwang, Su-Kyeong

    2015-01-01

    Early-onset epileptic encephalopathies are one of the most severe early onset epilepsies that can lead to progressive psychomotor impairment. These syndromes result from identifiable primary causes, such as structural, neurodegenerative, metabolic, or genetic defects, and an increasing number of novel genetic causes continue to be uncovered. A typical diagnostic approach includes documentation of anamnesis, determination of seizure semiology, electroencephalography, and neuroimaging. If primary biochemical investigations exclude precipitating conditions, a trial with the administration of a vitaminic compound (pyridoxine, pyridoxal-5-phosphate, or folinic acid) can then be initiated regardless of presumptive seizure causes. Patients with unclear etiologies should be considered for a further workup, which should include an evaluation for inherited metabolic defects and genetic analyses. Targeted next-generation sequencing panels showed a high diagnostic yield in patients with epileptic encephalopathy. Mutations associated with the emergence of epileptic encephalopathies can be identified in a targeted fashion by sequencing the most likely candidate genes. Next-generation sequencing technologies offer hope to a large number of patients with cryptogenic encephalopathies and will eventually lead to new therapeutic strategies and more favorable long-term outcomes. PMID:26692875

  5. Classification of convulsive psychogenic non-epileptic seizures using muscle transforms obtained from accelerometry signal.

    PubMed

    Kusmakar, Shitanshu; Gubbi, Jayavardhana; Yan, Bernard; O'Brien, Terence J; Palaniswami, Marimuthu

    2015-08-01

    Convulsive psychogenic non-epileptic seizure (PNES) can be characterized as events which mimics epileptic seizures but do not show any characteristic changes on electroencephalogram (EEG). Correct diagnosis requires video-electroencephalography monitoring (VEM) as the diagnosis of PNES is extremely difficult in primary health care. Recent work has demonstrated the usefulness of accelerometry signal taken during a seizure in classification of PNES. In this work, a new direction has been explored to understand the role of different muscles in PNES. This is achieved by modeling the muscle activity of ten different upper limb muscles as a resultant function of accelerometer signal. Using these models, the accelerometer signals recorded from convulsive epileptic patients were transformed into individual muscle components. Based on this, an automated algorithm for classification of convulsive PNES is proposed. The algorithm calculates four wavelet domain features based on signal power, approximate entropy, kurtosis and signal skewness. These features were then used to build a classification model using support vector machines (SVM) classifier. It was found that the transforms corresponding to anterior deltoid and brachioradialis results in good PNES classification accuracy. The algorithm showed a high sensitivity of 93.33% and an overall PNES classification accuracy of 89% with the transform corresponding to anterior deltoid. PMID:26736329

  6. Early-onset epileptic encephalopathies and the diagnostic approach to underlying causes.

    PubMed

    Hwang, Su-Kyeong; Kwon, Soonhak

    2015-11-01

    Early-onset epileptic encephalopathies are one of the most severe early onset epilepsies that can lead to progressive psychomotor impairment. These syndromes result from identifiable primary causes, such as structural, neurodegenerative, metabolic, or genetic defects, and an increasing number of novel genetic causes continue to be uncovered. A typical diagnostic approach includes documentation of anamnesis, determination of seizure semiology, electroencephalography, and neuroimaging. If primary biochemical investigations exclude precipitating conditions, a trial with the administration of a vitaminic compound (pyridoxine, pyridoxal-5-phosphate, or folinic acid) can then be initiated regardless of presumptive seizure causes. Patients with unclear etiologies should be considered for a further workup, which should include an evaluation for inherited metabolic defects and genetic analyses. Targeted next-generation sequencing panels showed a high diagnostic yield in patients with epileptic encephalopathy. Mutations associated with the emergence of epileptic encephalopathies can be identified in a targeted fashion by sequencing the most likely candidate genes. Next-generation sequencing technologies offer hope to a large number of patients with cryptogenic encephalopathies and will eventually lead to new therapeutic strategies and more favorable long-term outcomes. PMID:26692875

  7. Antioxidants as a Preventive Treatment for Epileptic Process: A Review of the Current Status

    PubMed Central

    Martinc, Boštjan; Grabnar, Iztok; Vovk, Tomaž

    2014-01-01

    Epilepsy is known as one of the most frequent neurological diseases, characterized by an enduring predisposition to generate epileptic seizures. Oxidative stress is believed to directly participate in pathways leading to neurodegeneration, which serves as the most important propagating factor, leading to the epileptic condition and cognitive decline. Moreover, there is also a growing body of evidence showing the disturbance of antioxidant system balance and consequently increased production of reactive species in patients with epilepsy. A meta-analysis, conducted in the present review confirms an association between epilepsy and increased lipid peroxidation. Furthermore, it was also shown that some of the antiepileptic drugs could potentially be responsible for additionally increased lipid peroxidation. Therefore, it is reasonable to propose that during the epileptic process neuroprotective treatment with antioxidants could lead to less sever structural damages, reduced epileptoge