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Sample records for epileptic human hippocampus

  1. Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus.

    PubMed

    Arellano, J I; Muñoz, A; Ballesteros-Yáñez, I; Sola, R G; DeFelipe, J

    2004-01-01

    Impairment of GABA-mediated inhibition is one of the main hypotheses invoked to explain seizure activity, both in experimental models and in human epilepsy. We have studied the distribution and the neurochemical characteristics of certain GABAergic circuits in the normal and epileptic human sclerotic hippocampal formation. We have focused our attention mainly on chandelier cells because, together with basket cells, they are considered to have powerful effects on spike generation. Chandelier cells represent a unique type of interneuron whose axon terminals (Ch-terminals) form synapses with the axon initial segments of cortical pyramidal cells and granular cells of the dentate gyrus. Different neurochemical subpopulations of chandelier cells have been identified by immunocytochemistry, mainly in the neocortex. Markers for Ch-terminals include the GABA transporter 1 (GAT-1), the polysialylated form of the cell-surface glycoprotein neural cell adhesion molecule (PSA-NCAM) and the calcium-binding proteins parvalbumin (PV) and calbindin D-28k (CB). In the normal hippocampal formation, GAT-1- and PV-immunoreactive (-ir) Ch-terminals were identified in the granular and polymorphic layers of the dentate gyrus, in the strata pyramidale and oriens of the CA fields, and in the pyramidal layer of the subicular complex. In addition, and in contrast to the hippocampus and dentate gyrus, subsets of Ch-terminals in the upper pyramidal layer of the normal subiculum express CB and PSA-NCAM. The sclerotic hippocampus of epileptic patients presented an impressive morphological and neurochemical reorganization of Ch-terminals and basket formations. This was apparent in the dentate gyrus and hippocampal formation, but not in the subiculum, which appeared to remain unaltered. Principally, numerous and more complex PV- and CB-ir Ch-terminals, as well as dense PV-ir basket formations, appeared in some hippocampal segments, whereas in other regions there was a lack of labelled elements

  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

    Johnson, Michael R; Behmoaras, Jacques; Bottolo, Leonardo; Krishnan, Michelle L; Pernhorst, Katharina; Santoscoy, Paola L Meza; 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.

  4. 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

  5. [Cell signaling in the epileptic hippocampus].

    PubMed

    Ferrer, I

    Cell signaling commanding death or survival in human epileptic hippocampus is difficult to trace because of the long interval between the beginning of symptoms and the sampling of damaged cerebral tissue for neuropathological examination. Intraperitoneal injection of the glutamate analogue kainic acid (KA) is a useful tool to analyze the effects of seizures and the excitotoxic damage in the rodent hippocampus. KA acts on NMDA and KA receptors, whereas it has little impact on AMPA receptors. Neurons of the hilus and CA3 neurons are primary targets of KA, although parvalbumin containing GABAergic neurons are less vulnerable than glutamatergic neurons. Immediate responses to KA are hsp 70 mRNA induction and HSP 70/72 protein expression, as well as c fos and c jun mRNA, and c Fos and c Jun protein expression in the hippocampus. Yet increased c Fos and c Jun expression is not a predictor of cell death or cell survival. In contrast, the tissular plasminogen activator (tPA) and the membrane Fas/Fas L signaling pathway probably have a role in facilitating cell death following KA injection. The involvement of other pathways remains controversial. Increased expression of the pro apoptotic Bax together with decreased Bcl 2 suggests Bax mediated apoptosis. Activation of the mitochondrial pathway includes leakage of citochrome c to the cytosol and activation of the caspase cascade leading to apoptosis. However, other studies have emphasized the limited expression of caspase 3, the main executioner of apoptosis, and the relevance of necrosis as the main form of cell death following KA excitotoxicity. Phosphorylation dependent activation of several kinases, including MAPK, p 38 and JNK/SAPK, and their substrates has been found in KA treated animals. Decreased CREBp expression is associated with cell death whereas increased ATF 2P and Elk 1P are associated with cell survival. Trophic factors probably do not play a significant role during the early stages of hippocanmpal damage but

  6. Differential vulnerability of interneurons in the epileptic hippocampus.

    PubMed

    Marx, Markus; Haas, Carola A; Häussler, Ute

    2013-01-01

    The loss of hippocampal interneurons has been considered as one reason for the onset of temporal lobe epilepsy (TLE) by shifting the excitation-inhibition balance. Yet, there are many different interneuron types which show differential vulnerability in the context of an epileptogenic insult. We used the intrahippocampal kainate (KA) mouse model for TLE in which a focal, unilateral KA injection induces status epilepticus (SE) followed by development of granule cell dispersion (GCD) and hippocampal sclerosis surrounding the injection site but not in the intermediate and temporal hippocampus. In this study, we characterized the loss of interneurons with respect to septotemporal position and to differential vulnerability of interneuron populations. To this end, we performed intrahippocampal recordings of the initial SE, in situ hybridization for glutamic acid decarboxylase 67 (GAD67) mRNA and immunohistochemistry for parvalbumin (PV) and neuropeptide Y (NPY) in the early phase of epileptogenesis at 2 days and at 21 days after KA injection, when recurrent epileptic activity and GCD have fully developed. We show that SE extended along the entire septotemporal axis of both hippocampi, but was stronger at distant sites than at the injection site. There was an almost complete loss of interneurons surrounding the injection site and expanding to the intermediate hippocampus already at 2 days but increasing until 21 days after KA. Furthermore, we observed differential vulnerability of PV- and NPY-expressing cells: while the latter were lost at the injection site but preserved at intermediate sites, PV-expressing cells were gone even at sites more temporal than GCD. In addition, we found upregulation of GAD67 mRNA expression in dispersed granule cells and of NPY staining in ipsilateral granule cells and ipsi- and contralateral mossy fibers. Our data thus indicate differential survival capacity of interneurons in the epileptic hippocampus and compensatory plasticity mechanisms

  7. 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

  8. Upregulation of 5-HT2C receptors in hippocampus of pilocarpine-induced epileptic rats: antagonism by Bacopa monnieri.

    PubMed

    Krishnakumar, Amee; Nandhu, M S; Paulose, C S

    2009-10-01

    Emotional disturbances, depressive mood, anxiety, aggressive behavior, and memory impairment are the common psychiatric features associated with temporal lobe epilepsy (TLE). The present study was carried out to investigate the role of Bacopa monnieri extract in hippocampus of pilocarpine-induced temporal lobe epileptic rats through the 5-HT(2C) receptor in relation to depression. Our results showed upregulation of 5-HT(2C) receptors with a decreased affinity in hippocampus of pilocarpine-induced epileptic rats. Also, there was an increase in 5-HT(2C) gene expression and inositol triphosphate content in epileptic hippocampus. Carbamazepine and B. monnieri treatments reversed the alterations in 5-HT(2C) receptor binding, gene expression, and inositol triphosphate content in treated epileptic rats as compared to untreated epileptic rats. The forced swim test confirmed the depressive behavior pattern during epilepsy that was nearly completely reversed by B. monnieri treatment.

  9. Behavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri.

    PubMed

    Mathew, Jobin; Gangadharan, Gireesh; Kuruvilla, Korah P; Paulose, C S

    2011-01-01

    In the present study, alterations of the General GABA and GABA(A) receptors in the hippocampus of pilocarpine-induced temporal lobe epileptic rats and the therapeutic application of Bacopa monnieri and its active component Bacoside-A were investigated. Bacopa monnieri (Linn.) is a herbaceous plant belonging to the family Scrophulariaceae. Hippocampus is the major region of the brain belonging to the limbic system and plays an important role in epileptogenesis, memory and learning. Scatchard analysis of [³H]GABA and [³H]bicuculline in the hippocampus of the epileptic rat showed significant decrease in B(max) (P < 0.001) compared to control. Real Time PCR amplification of GABA(A) receptor sub-units such as GABA(Aά₁), GABA(Aά₅) GABA(Aδ), and GAD were down regulated (P < 0.001) in the hippocampus of the epileptic rats compared to control. GABA(Aγ) subunit was up regulated. Epileptic rats have deficit in the radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses all these changes near to control. Our results suggest that decreased GABA receptors in the hippocampus have an important role in epilepsy associated behavioral deficit, Bacopa monnieri and Bacoside-A have clinical significance in the management of epilepsy.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. The influence of potassium concentration on epileptic seizures in a coupled neuronal model in the hippocampus.

    PubMed

    Du, Mengmeng; Li, Jiajia; Wang, Rong; Wu, Ying

    2016-10-01

    Experiments on hippocampal slices have recorded that a novel pattern of epileptic seizures with alternating excitatory and inhibitory activities in the CA1 region can be induced by an elevated potassium ion (K(+)) concentration in the extracellular space between neurons and astrocytes (ECS-NA). To explore the intrinsic effects of the factors (such as glial K(+) uptake, Na(+)-K(+)-ATPase, the K(+) concentration of the bath solution, and K(+) lateral diffusion) influencing K(+) concentration in the ECS-NA on the epileptic seizures recorded in previous experiments, we present a coupled model composed of excitatory and inhibitory neurons and glia in the CA1 region. Bifurcation diagrams showing the glial K(+) uptake strength with either the Na(+)-K(+)-ATPase pump strength or the bath solution K(+) concentration are obtained for neural epileptic seizures. The K(+) lateral diffusion leads to epileptic seizure in neurons only when the synaptic conductance values of the excitatory and inhibitory neurons are within an appropriate range. Finally, we propose an energy factor to measure the metabolic demand during neuron firing, and the results show that different energy demands for the normal discharges and the pathological epileptic seizures of the coupled neurons.

  16. The influence of potassium concentration on epileptic seizures in a coupled neuronal model in the hippocampus.

    PubMed

    Du, Mengmeng; Li, Jiajia; Wang, Rong; Wu, Ying

    2016-10-01

    Experiments on hippocampal slices have recorded that a novel pattern of epileptic seizures with alternating excitatory and inhibitory activities in the CA1 region can be induced by an elevated potassium ion (K(+)) concentration in the extracellular space between neurons and astrocytes (ECS-NA). To explore the intrinsic effects of the factors (such as glial K(+) uptake, Na(+)-K(+)-ATPase, the K(+) concentration of the bath solution, and K(+) lateral diffusion) influencing K(+) concentration in the ECS-NA on the epileptic seizures recorded in previous experiments, we present a coupled model composed of excitatory and inhibitory neurons and glia in the CA1 region. Bifurcation diagrams showing the glial K(+) uptake strength with either the Na(+)-K(+)-ATPase pump strength or the bath solution K(+) concentration are obtained for neural epileptic seizures. The K(+) lateral diffusion leads to epileptic seizure in neurons only when the synaptic conductance values of the excitatory and inhibitory neurons are within an appropriate range. Finally, we propose an energy factor to measure the metabolic demand during neuron firing, and the results show that different energy demands for the normal discharges and the pathological epileptic seizures of the coupled neurons. PMID:27668019

  17. Human Hippocampus Arbitrates Approach-Avoidance Conflict

    PubMed Central

    Bach, Dominik R.; Guitart-Masip, Marc; Packard, Pau A.; Miró, Júlia; Falip, Mercè; Fuentemilla, Lluís; Dolan, Raymond J.

    2014-01-01

    Summary Animal models of human anxiety often invoke a conflict between approach and avoidance [1, 2]. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus [2–6]. Efforts to translate these approaches to clinical contexts [7, 8] are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate [9]. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus [10]. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus. PMID:24560572

  18. 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

  19. Effect of topiramate on interleukin 6 expression in the hippocampus of amygdala-kindled epileptic rats

    PubMed Central

    YE, FEI; CHEN, XU-QIN; BAO, GUAN-SHUI; HUA, YIN; WANG, ZHE-DONG; BAO, YI-CHUAN

    2014-01-01

    The objective of this study was to analyze the changes in expression and the possible functions of interleukin-6 (IL-6) in electrical kindling of the basolateral amygdala (BLA) in epileptic rats. Bipolar electrodes were implanted into the BLA of Sprague-Dawley rats, and the rats were then subjected to chronic electrical stimulation through the electrodes to induce kindling. The seizure characteristics and behavioral changes of the rats were observed, and electroencephalograms were recorded during and following kindling. The IL-6 mRNA expression in the hippocampi of the rats was analyzed using semi-quantitative reverse transcription-polymerase chain reaction, and control and topiramate (TPM)-treated groups were compared. The mean time-period required for kindling was 13.50±3.99 days, and the afterdischarge duration (ADD) measured between 21,450 and 119,720 msec. The expression of IL-6 mRNA was significantly upregulated in the kindled rats. TPM was able to depress the seizures and decrease the IL-6 level in the kindled rats. In conclusion, IL-6 mRNA was upregulated in the hippocampi of epileptic rats, and IL-6 may have participated in the process of kindling. PMID:24348794

  20. Lipofuscin Granules in the Epileptic Human Temporal Neocortex with Age.

    PubMed

    Merlo, Suélen; Nakayama, Ana Beatriz S; Brusco, Janaina; Rossi, Marcos A; Carlotti, Carlos G; Moreira, Jorge E

    2015-01-01

    Lipofuscin granules (LGs), the "age pigments", are autofluorescent cell products from lysosomes that diverge in number and size among brain regions. Human temporal cortex from 20- to 55-year-old epileptic subjects were studied with the fat soluble dye Sudan Black, under confocal and electron microscopy. Ultrastructural analysis showed that with age LGs increase in area, but not in number. Proportionally to the LGs area, the electron lucid portion increases and the electron dense reduces over time. The robust increase in lipid components is possibly due to modifications in the neuronal metabolism with age in physiological and pathological conditions.

  1. Decoding Neuronal Ensembles in the Human Hippocampus

    PubMed Central

    Hassabis, Demis; Chu, Carlton; Rees, Geraint; Weiskopf, Nikolaus; Molyneux, Peter D.; Maguire, Eleanor A.

    2009-01-01

    Summary Background The hippocampus underpins our ability to navigate, to form and recollect memories, and to imagine future experiences. How activity across millions of hippocampal neurons supports these functions is a fundamental question in neuroscience, wherein the size, sparseness, and organization of the hippocampal neural code are debated. Results Here, by using multivariate pattern classification and high spatial resolution functional MRI, we decoded activity across the population of neurons in the human medial temporal lobe while participants navigated in a virtual reality environment. Remarkably, we could accurately predict the position of an individual within this environment solely from the pattern of activity in his hippocampus even when visual input and task were held constant. Moreover, we observed a dissociation between responses in the hippocampus and parahippocampal gyrus, suggesting that they play differing roles in navigation. Conclusions These results show that highly abstracted representations of space are expressed in the human hippocampus. Furthermore, our findings have implications for understanding the hippocampal population code and suggest that, contrary to current consensus, neuronal ensembles representing place memories must be large and have an anisotropic structure. PMID:19285400

  2. 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.

  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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. Neurofunctional topography of the human hippocampus.

    PubMed

    Robinson, Jennifer L; Barron, Daniel S; Kirby, Lauren A J; Bottenhorn, Katherine L; Hill, Ashley C; Murphy, Jerry E; Katz, Jeffrey S; Salibi, Nouha; Eickhoff, Simon B; Fox, Peter T

    2015-12-01

    Much of what was assumed about the functional topography of the hippocampus was derived from a single case study over half a century ago. Given advances in the imaging sciences, a new era of discovery is underway, with potential to transform the understanding of healthy processing as well as the ability to treat disorders. Coactivation-based parcellation, a meta-analytic approach, and ultra-high field, high-resolution functional and structural neuroimaging to characterize the neurofunctional topography of the hippocampus was employed. Data revealed strong support for an evolutionarily preserved topography along the long-axis. Specifically, the left hippocampus was segmented into three distinct clusters: an emotional processing cluster supported by structural and functional connectivity to the amygdala and parahippocampal gyrus, a cognitive operations cluster, with functional connectivity to the anterior cingulate and inferior frontal gyrus, and a posterior perceptual cluster with distinct structural connectivity patterns to the occipital lobe coupled with functional connectivity to the precuneus and angular gyrus. The right hippocampal segmentation was more ambiguous, with plausible 2- and 5-cluster solutions. Segmentations shared connectivity with brain regions known to support the correlated processes. This represented the first neurofunctional topographic model of the hippocampus using a robust, bias-free, multimodal approach.

  9. 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

  10. 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

  11. Sleep-dependent directional coupling between human neocortex and hippocampus.

    PubMed

    Wagner, Tobias; Axmacher, Nikolai; Lehnertz, Klaus; Elger, Christian E; Fell, Jürgen

    2010-02-01

    Complex interactions between neocortex and hippocampus are the neural basis of memory formation. Two-step theories of memory formation suggest that initial encoding of novel information depends on the induction of rapid plasticity within the hippocampus, and is followed by a second sleep-dependent step of memory consolidation. These theories predict information flow from the neocortex into the hippocampus during waking state and in the reverse direction during sleep. However, experimental evidence that interactions between hippocampus and neocortex have a predominant direction which reverses during sleep rely on cross-correlation analysis of data from animal experiments and yielded inconsistent results. Here, we investigated directional coupling in intracranial EEG data from human subjects using a phase-modeling approach which is well suited to reveal functional interdependencies in oscillatory data. In general, we observed that the anterior hippocampus predominantly drives nearby and remote brain regions. Surprisingly, however, the influence of neocortical regions on the hippocampus significantly increased during sleep as compared to waking state. These results question the standard model of hippocampal-neocortical interactions and suggest that sleep-dependent consolidation is accomplished by an active retrieval of hippocampal information by the neocortex.

  12. Epilepsy but not mobile phone frequency (900 MHz) induces apoptosis and calcium entry in hippocampus of epileptic rat: involvement of TRPV1 channels.

    PubMed

    Nazıroğlu, Mustafa; Özkan, Fatma Feyza; Hapil, Seher Rabia; Ghazizadeh, Vahid; Çiğ, Bilal

    2015-02-01

    Electromagnetic radiation (EMR) and epilepsy are reported to mediate the regulation of apoptosis and oxidative stress through Ca(2+) influx. Results of recent reports indicated that EMR can increase temperature and oxidative stress of body cells, and TRPV1 channel is activated by noxious heat, oxidative stress, and capsaicin (CAP). We investigated the effects of mobile phone (900 MHz) EMR exposure on Ca(2+) influx, apoptosis, oxidative stress, and TRPV1 channel activations in the hippocampus of pentylenetetrazol (PTZ)-induced epileptic rats. Freshly isolated hippocampal neurons of twenty-one rats were used in study within three groups namely control, PTZ, and PTZ + EMR. The neurons in the three groups were stimulated by CAP. Epilepsy was induced by PTZ administration. The neurons in PTZ + EMR group were exposed to the 900 MHz EMR for 1 h. The apoptosis, mitochondrial membrane depolarization, intracellular reactive oxygen species (ROS), and caspase-3 and caspase-9 values were higher in PTZ and PTZ + EMR groups than in control. However, EMR did not add additional increase effects on the values in the hippocampal neurons. Intracellular-free Ca(2+) concentrations in fura-2 analyses were also higher in PTZ + CAP group than in control although their concentrations were decreased by TRPV1 channel blocker, capsazepine. However, there were no statistical changes on the Ca(2+) concentrations between epilepsy and EMR groups. In conclusion, apoptosis, mitochondrial, ROS, and Ca(2+) influx via TRPV1 channel were increased in the hippocampal neurons by epilepsy induction although the mobile phone did not change the values. The results indicated that TRPV1 channels in hippocampus may possibly be a novel target for effective target of epilepsy.

  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. 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

  15. 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

  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. 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

  18. 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

  19. Epigenetic mechanisms underlying human epileptic disorders and the process of epileptogenesis

    PubMed Central

    Qureshi, Irfan A.; Mehler, Mark F.

    2010-01-01

    The rapidly emerging science of epigenetics and epigenomic medicine promises to reveal novel insights into the susceptibility to and the onset and progression of epileptic disorders. Epigenetic regulatory mechanisms are now implicated in orchestrating aspects of neural development (e.g., cell fate specification and maturation), homeostasis and stress responses (e.g., immediate early gene transcription), and neural network function (e.g., excitation-inhibition coupling and activity-dependent plasticity). These same neurobiological processes are responsible for determining the heterogeneous features of complex epileptic disease states. Thus, we highlight recent evidence that is beginning to elucidate the specific roles played by epigenetic mechanisms, including DNA methylation, histone code modifications and chromatin remodeling, non-coding RNAs and RNA editing, in human epilepsy syndromes and in the process of epileptogenesis. The highly integrated layers of the epigenome are responsible for the cell type specific and exquisitely environmentally responsive deployment of genes and functional gene networks that underlie the molecular pathophysiology of epilepsy and its associated co-morbidities, including but not limited to neurotransmitter receptors (e.g, GluR2, GLRA2, and GLRA3), growth factors (e.g, BDNF), extracellular matrix proteins (e.g., RELN) and diverse transcriptional regulators (e.g., CREB, c-fos, and c-jun). These important observations suggest that future epigenetic studies are necessary to better understand, classify, prevent and treat epileptic disorders. PMID:20188170

  20. 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.

  1. 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

  2. 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,…

  3. 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

  4. 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

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

    PubMed

    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

    2015-02-01

    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.

  6. 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

  7. 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

  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. 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

  10. 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

  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. [Synaptic structure of human cerebral cortex in chronic hypoxia and epileptic changes in the brain].

    PubMed

    Semchenko, V V; Ereniev, S I; Stepanov, S S; Genne, R I

    1990-07-01

    Comparative quantitative analysis of the synaptic pool of the neuropil in the molecular layer at the temporal epilepsy and cerebral chronic hypoxia (brain tumor, that is not accompanied with a convulsive syndrome) has been performed using biopsy material. As a control the brain of practically healthy persons, who died a sudden death, has been used. The contrasting method of the phosphoric tungsten acid alcohol solution and OsO4 has been applied. An essential complication in the cerebral cortex synaptic structure in the zone with a regular epileptic activity, as well as preservation of quantitative density of synapses near to the control level at epilepsy have been revealed. At the chronic hypoxia simplification in organization of interneuronal connections at the level of synapses and reduction in the quantitative density of synapses have been noted. The complication of the cerebral cortex synaptic structure and epileptic changes++ of the brain is considered as an increase in the neuropil informativity, contributing to keeping a long-term memory about the character of epileptic manifestations.

  13. Nestin-expressing cells in the human hippocampus.

    PubMed

    Kruglyakova, E P; Khovryakov, A V; Shikhanov, N P; Maccann, G M; Vael', Ikhsan; Kruglyakov, P P; Sosunov, A A

    2005-11-01

    Nestin, a protein of the intermediate filament family, is typical of undifferentiated neural stem and progenitor cells. The present report describes studies of nestin expression in the hippocampus of patients with epilepsy and identifies five types of nestin-immunopositive cells differing in terms of their morphological phenotype and immunological characteristics. These were cells with the phenotype of radial glial cells, bipolar cells, small dendritic cells, cells of the subependymal zone, and astrocyte-like cells. Two types of cell - radial gliocytes of the dentate fascia and NG2-immunopositive bipolar cells - can be regarded as neural precursors of different levels of commitment.

  14. 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

  15. Pharmacoresistant temporal lobe epilepsy modifies histamine turnover and H3 receptor function in the human hippocampus and temporal neocortex.

    PubMed

    Bañuelos-Cabrera, Ivette; Cuéllar-Herrera, Manola; Velasco, Ana Luisa; Velasco, Francisco; Alonso-Vanegas, Mario; Carmona, Francia; Guevara, Rosalinda; Arias-Montaño, José-Antonio; Rocha, Luisa

    2016-04-01

    Experiments were designed to evaluate the tissue content of tele-methylhistamine (t-MeHA) and histamine as well as H3 receptor (H3 Rs) binding and activation of the heterotrimeric guanine nucleotide binding αi/o proteins (Gαi/o) coupled to these receptors in the hippocampus and temporal neocortex of patients (n = 10) with pharmacoresistant mesial temporal lobe epilepsy (MTLE). Patients with MTLE showed elevated tissue content of t-MeHA in the hippocampus. Analyses revealed that a younger age at seizure onset was correlated with a higher tissue content of t-MeHA, lower H3 R binding, and lower efficacy of Gαi/o protein activation in the hippocampus. We conclude that the hippocampus shows a reduction in the H3 R function associated with enhanced histamine. In contrast, the temporal neocortex displayed a high efficacy of H3 Rs Gαi/o protein activation that was associated with low tissue contents of histamine and t-MeHA. These results indicate an overactivation of H3 Rs leading to decreased histamine in the temporal neocortex. However, this situation was lessened in circumstances such as a longer duration of epilepsy or higher seizure frequency. It is concluded that decrease in H3 Rs function and enhanced levels of histamine may contribute to the epileptic activity in the hippocampus and temporal neocortex of patients with pharmacoresistant MTLE.

  16. 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

  17. Evaluation of epileptic dogs as an animal model of human epilepsy.

    PubMed

    Löscher, W; Schwartz-Porsche, D; Frey, H H; Schmidt, D

    1985-01-01

    In 126 epileptic dogs with spontaneously recurring generalized tonic-clonic (grand mal) seizures, epidemiological aspects and the efficacy of chronic oral treatment with common antiepileptic drugs were studied. Furthermore, the pharmacokinetics of antiepileptic drugs in dogs was compared with the values known for man. As in man, idiopathic epilepsy appeared to be more common than symptomatic epilepsy in dogs. There was a preponderance of male vs. female animals. When the breeds of the epileptic dogs were compared to the distribution of breeds in the hospital population, breed-related differences in the prevalence of epilepsy were found. The highest prevalence was seen in Cocker spaniels, Miniature schnauzers, Collies and Bassets. The total prevalence of dogs with epilepsy was 0.55%. Comparison of pharmacokinetics of antiepileptic drugs showed that some drugs were suited for maintenance therapy in dogs (primidone, phenobarbital, ethosuximide, trimethadione) whereas others appeared not to be ideally suited because of their short half-lives (phenytoin, carbamazepine, valproic acid, diazepam, clonazepam, nitrazepam). This was confirmed by the evaluation of antiepileptic drug efficacy in epileptic dogs. 46 dogs were treated with primidone at daily doses of 14-104 mg/kg for 6-60 months. During medication with primidone, effective plasma levels of its metabolite phenobarbital could be maintained. Complete control of seizures or a reduction of seizure frequency by at least 75% was achieved in 39% of the dogs at phenobarbital concentrations of 5-49 micrograms/ml. Similar figures were obtained during chronic treatment with phenobarbital at daily doses of 2.5-13 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

  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.

  19. 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…

  20. 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.

  1. 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.

  2. Developmental profile of neurogenesis in prenatal human hippocampus: an immunohistochemical study.

    PubMed

    Yang, Pengbo; Zhang, Junfeng; Shi, Hangyu; Zhang, Jianshui; Xu, Xi; Xiao, Xinli; Liu, Yong

    2014-11-01

    Hippocampus has attracted the attention of the neuroscientists for its involvement in a wide spectrum of higher-order brain functions and pathological conditions, especially its persistent neurogenesis in subgranular zone (SGZ). The development of hippocampus was intensively investigated on animals such as rodents. However, in prenatal human hippocampus, little information on the distribution of neural stem/progenitor cells, newly generated neurons and mature neurons is available and the timetable of a series of neurogenesis event is even more obscure. So in the present study, we aim at immunohistochemically providing more information on neurogenesis in prenatal human hippocampus from 9 weeks to 32 weeks of gestation. We found that the ki67-positive cells were always detected in hippocampus from 9 weeks to 32 weeks, with a peak at 9 weeks in cornu ammonis (CA) or 14 weeks in dentate gyrus (DG). At 9 weeks the nestin-expressing cells were distributed throughout the hippocampus, with concentrated immunoreactivity in intermediate zone (IZ), marginal zone (MZ), fimbria, and relatively sparse immunoreactivity in the ventricular zone (VZ) and hippocampal plate (HP). With development, the optical density (OD) and the number of nestin-positive cells decreased gradually. At 32 weeks, there were relatively more nestin-positive cells in DG than that in CA. About DCX-positive cells, they displayed a similar distribution as nestin-positive cells (immunoreactivity concentrated in IZ, MZ, fimbria and HP) and a dramatic decrease of OD or cell number density from 9 weeks on. NeuN-positive cells, with small nuclei, were firstly found in MZ and subplate of hippocampus at 9 weeks. After 14 weeks, many NeuN-positive cells extended from subplate into HP and the density of NeuN-positive cells peaked at 22 weeks. That the immunoreactivity for NeuN was the strongest and the nuclei were the biggest at 32 weeks suggests that the neurons reach maturity gradually. Therefore this study provides

  3. 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

  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. 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.

  6. Neuropeptides: anticonvulsant and convulsant mechanisms in epileptic model systems and in humans.

    PubMed

    Bajorek, J G; Lee, R J; Lomax, P

    1986-01-01

    Neuropeptides represent a new class of compounds with important implications for the understanding of the mechanisms and treatment of epileptic disorders. Several systems of peptide modulators--in particular the opioid-like peptides, vasopressin, somatostatin, thyrotropin-releasing hormone (TRH) and ACTH--have partially demonstrated endogenous roles in some forms of epilepsy. Seizures and stressful situations may release endogenous opioid peptides and mediate postictal depression and postictal seizure refractoriness. Vasopressin is believed to increase susceptibility to convulsions and may be involved in the pathogenesis of febrile convulsions. Derangements in TRH regulation may lower thresholds for seizure expression by regulating arousal systems; however, some TRH analogs have proven to be effective anticonvulsants. Long-term alterations in somatostatin regulation could be components of focal epilepsies. ACTH is particularly useful in the treatment of infantile spasms. Pharmacological effects of these and other peptides have potentials for defining new classes of anticonvulsants. Cholecystokinin (CCK) and its analogs, the opioid peptides beta-endorphin and FK33824, TRH analogs, and several dipeptides exhibit potent anticonvulsant properties in chemical, electroshock, and genetic model screens. Convulsant actions of CRF, somatostatin, TRH, vasopressin, and high doses of endorphin or enkephalins may provide new tools to study regulatory mechanisms of cerebral excitability. The enkephalin epileptogenic effect is being developed as a predictive tool for new anti-petit mal anticonvulsants. Advances in molecular biology have identified the genes of particular peptide families. A concept has developed that the large propeptide precursors, coded by these genes, whose processing leads to functional peptide formation and release, regulate peptidergic humoral responses to external stimuli. This idea may have particular application in the understanding of the genetic basis

  7. 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

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

    PubMed

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

    2015-09-01

    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.

  9. 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

  10. Synaptic vesicle protein2A decreases in amygdaloid-kindling pharmcoresistant epileptic rats.

    PubMed

    Shi, Jing; Zhou, Feng; Wang, Li-kun; Wu, Guo-feng

    2015-10-01

    Synaptic vesicle protein 2A (SV2A) involvement has been reported in the animal models of epilepsy and in human intractable epilepsy. The difference between pharmacosensitive epilepsy and pharmacoresistant epilepsy remains poorly understood. The present study aimed to observe the hippocampus SV2A protein expression in amygdale-kindling pharmacoresistant epileptic rats. The pharmacosensitive epileptic rats served as control. Amygdaloid-kindling model of epilepsy was established in 100 healthy adult male Sprague-Dawley rats. The kindled rat model of epilepsy was used to select pharmacoresistance by testing their seizure response to phenytoin and phenobarbital. The selected pharmacoresistant rats were assigned to a pharmacoresistant epileptic group (PRE group). Another 12 pharmacosensitive epileptic rats (PSE group) served as control. Immunohistochemistry, real-time PCR and Western blotting were used to determine SV2A expression in the hippocampus tissue samples from both the PRE and the PSE rats. Immunohistochemistry staining showed that SV2A was mainly accumulated in the cytoplasm of the neurons, as well as along their dendrites throughout all subfields of the hippocampus. Immunoreactive staining level of SV2A-positive cells was 0.483 ± 0.304 in the PRE group and 0.866 ± 0.090 in the PSE group (P < 0.05). Real-time PCR analysis demonstrated that 2(-ΔΔCt) value of SV2A mRNA was 0.30 ± 0.43 in the PRE group and 0.76 ± 0.18 in the PSE group (P < 0.05). Western blotting analysis obtained the similar findings (0.27 ± 0.21 versus 1.12 ± 0.21, P < 0.05). PRE rats displayed a significant decrease of SV2A in the brain. SV2A may be associated with the pathogenesis of intractable epilepsy of the amygdaloid-kindling rats.

  11. Current issues on epileptic women.

    PubMed

    Pimentel, J

    2000-05-01

    Issues linked to epileptic women are being reviewed. Ovarian steroid hormones have a number of effects on the brain that predispose to epileptic activity. In particular, estradiol produces changes in the hippocampus synapses predisposing hyperexcitability associated with seizures. Also, menses and menopause periods, in which there are changing levels of steroid ovarian hormones, are associated with a particular appearing of seizures (catamenial epilepsy) and with phenotypic changes of previous ones. Epilepsy can affect the reproductive system, inducing endocrinal abnormalities (through disruption of cortical regulation of hypothalamus hormone release, and changes in the central nervous system concentration of steroid hormones induced by antiepileptics), infertility (linked to abnormalities in menstrual cycle or to the occurrence of polycytic ovaries, particularly in association with valproate treatment), and sexual disfunction (namely related to physiologic defects). Oral hormonal contraceptives should be performed using a pill with > 50mg of estrogen in order to prevent its potential loss of efficacy induced by enzyme-inducing antiepileptics. Concerning pregnancy, some topics should be discussed with, and advised to epileptic women, including: the possibility of withdrawal antiepileptics and the need of folic acid supplementation when planning a pregnancy; the risk of increased seizure frequency during pregnancy, and of the occurrence of obstetric complications; the increased risk of teratogenesis associated with antiepileptic therapy (mainly if in polytherapy); the need of vitamin K supplementation during the last month of pregnancy in order to avoid newborn haemorrhages; and the general absence of risk of breastfeeding even under sustained antiepileptic therapy. PMID:10828312

  12. 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

  13. The hippocampus codes the uncertainty of cue-outcome associations: an intracranial electrophysiological study in humans.

    PubMed

    Vanni-Mercier, Giovanna; Mauguière, François; Isnard, Jean; Dreher, Jean-Claude

    2009-04-22

    Learning to predict upcoming outcomes based on environmental cues is essential for adaptative behavior. In monkeys, midbrain dopaminergic neurons code two statistical properties of reward: a prediction error at the outcome and uncertainty during the delay period between cues and outcomes. Although the hippocampus is sensitive to reward processing, and hippocampal-midbrain functional interactions are well documented, it is unknown whether it also codes the statistical properties of reward information. To address this question, we recorded local field potentials from intracranial electrodes in human hippocampus while subjects learned to associate cues of slot machines with various monetary reward probabilities (P). We found that the amplitudes of negative event-related potentials covaried with uncertainty at the outcome, being maximal for P = 0.5 and minimal for P = 0 and P = 1, regardless of winning or not. These results show that the hippocampus computes an uncertainty signal that may constitute a fundamental mechanism underlying the role of this brain region in a number of functions, including attention-based learning, associative learning, probabilistic classification, and binding of stimulus elements.

  14. The hippocampus codes the uncertainty of cue-outcome associations: an intracranial electrophysiological study in humans.

    PubMed

    Vanni-Mercier, Giovanna; Mauguière, François; Isnard, Jean; Dreher, Jean-Claude

    2009-04-22

    Learning to predict upcoming outcomes based on environmental cues is essential for adaptative behavior. In monkeys, midbrain dopaminergic neurons code two statistical properties of reward: a prediction error at the outcome and uncertainty during the delay period between cues and outcomes. Although the hippocampus is sensitive to reward processing, and hippocampal-midbrain functional interactions are well documented, it is unknown whether it also codes the statistical properties of reward information. To address this question, we recorded local field potentials from intracranial electrodes in human hippocampus while subjects learned to associate cues of slot machines with various monetary reward probabilities (P). We found that the amplitudes of negative event-related potentials covaried with uncertainty at the outcome, being maximal for P = 0.5 and minimal for P = 0 and P = 1, regardless of winning or not. These results show that the hippocampus computes an uncertainty signal that may constitute a fundamental mechanism underlying the role of this brain region in a number of functions, including attention-based learning, associative learning, probabilistic classification, and binding of stimulus elements. PMID:19386925

  15. 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

  16. 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

  17. 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

  18. 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

    2015-09-18

    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.

  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. Is the HM story only a "remote memory"? Some facts about hippocampus and memory in humans.

    PubMed

    Deweer, B; Pillon, B; Pochon, J B; Dubois, B

    2001-12-14

    In this review, we argue that a number of current data support the notion that the hippocampal formations play an important role in episodic memory in humans. We will focus on data gathered from three topics within this field: (1) the neuropsychological study of memory in degenerative diseases, which provides striking dissociations of processes, as a function of the location of cerebral lesions and of their functional consequences; (2) the description of patients' memory difficulties after unilateral medial temporal lobectomy. Given the visuo-verbal dissociation, we may anticipate that the study of the effects of such lesions may help in the understanding of the role of the hippocampus in memory, in terms of: (i) the stage of memory processing where the hippocampus is really involved (encoding, consolidation and/or retrieval); (ii) the specificity of the impairments as a function of the nature (verbal vs. visuo-spatial) of the to-be-remembered material; (3) recent evidence from imaging studies: (i) the morphological approach, which provides interesting information with the study of correlations between the volumes of diverse cerebral regions-particularly the volume of the hippocampus-and episodic memory performance and other cognitive measures; (ii) metabolic studies, using PET scan, which were first designed for correlational analyses between performance in episodic memory tasks and glucose utilization at rest in diverse regions of interest, such as the hippocampal formations; (iii) activation studies with PET and functional MRI, which are actually more straightforward, since they allow correlations between the metabolism in regions of interest and performance on line (e.g. during encoding or retrieval of information). In our view, inasmuch as such different approaches-degenerative diseases, lesions or imagery-provide convergent information, they give renewed weight to the notion according to which the hippocampal formations are critically concerned in episodic

  2. 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

  3. Promoter variants determine γ-aminobutyric acid homeostasis-related gene transcription in human epileptic hippocampi.

    PubMed

    Pernhorst, Katharina; Raabe, Anna; Niehusmann, Pitt; van Loo, Karen M J; Grote, Alexander; Hoffmann, Per; Cichon, Sven; Sander, Thomas; Schoch, Susanne; Becker, Albert J

    2011-12-01

    The functional consequences of single nucleotide polymorphisms associated with episodic brain disorders such as epilepsy and depression are unclear. Allelic associations with generalized epilepsies have been reported for single nucleotide polymorphisms rs1883415 (ALDH5A1; succinic semialdehyde dehydrogenase) and rs4906902 (GABRB3; GABAA β3), both of which are present in the 5' regulatory region of genes involved in γ-aminobutyric acid (GABA) homeostasis. To address their allelic association with episodic brain disorders and allele-specific impact on the transcriptional regulation of these genes in human brain tissue, DNA and messenger RNA (mRNA) isolated from hippocampi were obtained at epilepsy surgery of 146 pharmacoresistant mesial temporal lobe epilepsy (mTLE) patients and from 651 healthy controls. We found that the C allele of rs1883415 is accumulated to a greater extentin mTLE versus controls. By real-time quantitative reverse transcription-polymerase chain reaction analyses, individuals homozygous for the C allele showed higher ALDH5A1 mRNA expression. The rs4906902 G allele of the GABRB3 gene was overrepresented in mTLE patients with depression; individuals homozygous for the G allele showed reduced GABRB3 mRNA expression. Bioinformatic analyses suggest that rs1883415 and rs4906902 alter the DNA binding affinity of the transcription factors Egr-3 in ALDH5A1 and MEF-2 in GABRB3 promoters, respectively. Using in vitro luciferase transfection assays, we observed that, in both cases, the transcription factors regulate gene expression depending on the allelic variant in the same direction as in the human hippocampi. Our data suggest that distinct promoter variants may sensitize individuals for differential, potentially stimulus-induced alterations of GABA homeostasis-relevant gene expression. This might contribute to the episodic onset of symptoms and point to new targets for pharmacotherapies.

  4. 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.

  5. 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

  6. Epileptic Encephalopathies: An Overview

    PubMed Central

    Khan, Sonia; Al Baradie, Raidah

    2012-01-01

    Epileptic encephalopathies are an epileptic condition characterized by epileptiform abnormalities associated with progressive cerebral dysfunction. In the classification of the International League Against Epilepsy eight age-related epileptic encephalopathy syndromes are recognized. These syndromes include early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, West syndrome and Dravet syndrome in infancy, myoclonic status in nonprogressive encephalopathies, and Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and epilepsy with continuous spike waves during slow wave sleep in childhood and adolescences. Other epileptic syndromes such as migrating partial seizures in infancy and severe epilepsy with multiple independent spike foci may be reasonably added. In this paper, we provide an overview of epileptic encephalopathies including clinical neurophysiological features, cognitive deterioration, and management options especially that these conditions are generally refractory to standard antiepileptic drugs. PMID:23213494

  7. Cerebral glucose utilization measured with high resolution positron emission tomography in epileptic Finnish Spitz dogs and healthy dogs.

    PubMed

    Viitmaa, Ranno; Haaparanta-Solin, Merja; Snellman, Marjatta; Cizinauskas, Sigitas; Orro, Toomas; Kuusela, Erja; Johansson, Jarkko; Viljanen, Tapio; Jokinen, Tarja S; Bergamasco, Luciana; Metsähonkala, Liisa

    2014-01-01

    In human epileptic patients, changes in cerebral glucose utilization can be detected 2-deoxy-2-[(18) F] fluoro-D-glucose positron emission tomography (FDG-PET). The purpose of this prospective study was to determine whether epileptic dogs might show similar findings. Eleven Finnish Spitz dogs with focal idiopathic epilepsy and six healthy dogs were included. Dogs were examined using electroencephalography (EEG) and FDG-PET, with epileptic dogs being evaluated during the interictal period. Visual and semi-quantitative assessment methods of FDG-PET were compared and contrasted with EEG findings. Three independent observers, unaware of dog clinical status, detected FDG-PET uptake abnormalities in 9/11 epileptic (82%), and 4/8 healthy dogs (50%). Occipital cortex findings were significantly associated with epileptic status (P = 0.013). Epileptic dogs had significantly lower standardized uptake values (SUVs) in numerous cortical regions, the cerebellum, and the hippocampus compared to the control dogs. The lowest SUVs were found in the occipital lobe. White matter normalized and left-right asymmetry index values for all pairs of homologous regions did not differ between groups. Visual evaluation of the EEGs was less sensitive (36%) than FDG-PET. Both diagnostic tests were consensual and specific (100%) for occipital findings, but EEG had a lower sensitivity for detecting lateralized foci than FDG-PET. Findings supported the use of FDG-PET as a diagnostic test for dogs with suspected idiopathic epilepsy. Visual and semiquantitative analyses of FDG-PET scans provided complementary information. Findings also supported the theory that epileptogenesis may occur in multiple brain regions in Finnish Spitz dogs with idiopathic epilepsy.

  8. 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

  9. 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.

  10. 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

  11. In-vivo Dynamics of the Human Hippocampus across the Menstrual Cycle

    PubMed Central

    Barth, Claudia; Steele, Christopher J; Mueller, Karsten; Rekkas, Vivien P.; Arélin, Katrin; Pampel, Andre; Burmann, Inga; Kratzsch, Jürgen; Villringer, Arno; Sacher, Julia

    2016-01-01

    Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies suggests similar subtle fluctuations in hippocampal structure, predominantly linked to estrogen. Hippocampal abnormalities have been observed in several neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential impact of subtle sex-hormonal fluctuations on human hippocampal structure in health is unclear. We tested the feasibility of longitudinal neuroimaging in conjunction with rigorous menstrual cycle monitoring to evaluate potential changes in hippocampal microstructure associated with physiological sex-hormonal changes. Thirty longitudinal diffusion weighted imaging scans of a single healthy female subject were acquired across two full menstrual cycles. We calculated hippocampal fractional anisotropy (FA), a measure sensitive to changes in microstructural integrity, and investigated potential correlations with estrogen. We observed a significant positive correlation between FA values and estrogen in the hippocampus bilaterally, revealing a peak in FA closely paralleling ovulation. This exploratory, single-subject study demonstrates the feasibility of a longitudinal DWI scanning protocol across the menstrual cycle and is the first to link subtle endogenous hormonal fluctuations to changes in FA in vivo. In light of recent attempts to neurally phenotype single humans, our findings highlight menstrual cycle monitoring in parallel with highly sampled individual neuroimaging data to address fundamental questions about the dynamics of plasticity in the adult brain. PMID:27713470

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

    PubMed Central

    Lee, Choong‐Hee; Ryu, Jungwon; Lee, Sang‐Hun; Kim, Hakjin

    2016-01-01

    ABSTRACT 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

  13. 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.

  14. 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

  15. Effect of Chaihu-Shugan-San on the mRNA expression of the 5-HT1A receptor and cellular proliferation in the hippocampus of epileptic rats with depression

    PubMed Central

    YANG, PING; LI, LIANG; LIU, XUE-JUN; CAI, XIONG; SUN, MEI-ZHEN; HE, JUN-FENG; ZENG, GUANG; HUANG, HUI-YONG

    2016-01-01

    Chaihu-Shugan-San (CHSGS) is a herbal preparation that has been shown to effectively relieve neurologic impairment and reduce depression. However, the efficacy of CHSGS in the treatment of patients with epilepsy with depression is unknown. Therefore, in the present study, adult rats were exposed to chronic mild stress following the establishment of chronic pilocarpine-induced epilepsy. Subsequently, a sucrose consumption test and open-field test (OFT) were performed to assess depression-like behavior. Rats were randomly divided into four groups: Control, model, fluoxetine (1.8 g/kg) and CHSGS (2.7 g/kg) groups. The control and model groups received normal saline. The mRNA expression levels of the 5-hydroxytryptamine 1A (5-HT1A) receptor and the number of 5-bromo-2′-deoxyuridine (BrdU)-labeled cells in the hippocampal dentate gyrus were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemical analysis, respectively. Treatment administration was conducted by once daily intragastric perfusion for 28 days. The mRNA expression levels of the 5-HT1A receptor, the number of BrdU-labeled cells in the hippocampal dentate gyrus, the consumption of sucrose, and frequency of vertical and horizontal movement scores in the OFT were enhanced in the fluoxetine and CHSGS groups compared with the model group (P<0.05). However, no statistically significant difference was detected between the fluoxetine and CHSGS groups. These data suggest that CHSGS is able to increase the expression of 5-HT1A receptor mRNA and cellular proliferation in the hippocampal dentate gyrus in epileptic rats with depression, and thus effectively improve certain symptoms of depression. PMID:26889228

  16. Analysis of Epileptic Seizures with Complex Network

    PubMed Central

    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

  17. The human hippocampus contributes to both the recollection and familiarity components of recognition memory

    PubMed Central

    Merkow, Maxwell B.; Burke, John F.; Kahana, Michael J.

    2015-01-01

    Despite a substantial body of work comprising theoretical modeling, the effects of medial temporal lobe lesions, and electrophysiological signal analysis, the role of the hippocampus in recognition memory remains controversial. In particular, it is not known whether the hippocampus exclusively supports recollection or both recollection and familiarity—the two latent cognitive processes theorized to underlie recognition memory. We studied recognition memory in a large group of patients undergoing intracranial electroencephalographic (iEEG) monitoring for epilepsy. By measuring high-frequency activity (HFA)—a signal associated with precise spatiotemporal properties—we show that hippocampal activity during recognition predicted recognition memory performance and tracked both recollection and familiarity. Through the lens of dual-process models, these results indicate that the hippocampus supports both the recollection and familiarity processes. PMID:26578784

  18. 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

  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.

  20. Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death.

    PubMed

    Danik, M; Chabot, J G; Mercier, C; Benabid, A L; Chauvin, C; Quirion, R; Suh, M

    1991-10-01

    Clone pTB16 has been isolated by differential screening of a human glioma cDNA library. Northern blot analysis has shown that pTB16 expression is several times (greater than 11-fold) higher in gliomas than in a primitive neuroectodermal tumor. This observation was supported by in situ hybridization and extended to nine other gliomas. Expression was virtually absent in adenocarcinoma cells metastasized to brain. Malignant gliomas showed stronger hybridization than benign gliomas, while blood capillaries did not show hybridization. pTB16 mRNA was also shown to be expressed in established glioma cell lines and at high levels in epileptic foci, indicating that expression of the gene may be limited to certain cell types and that its upregulation is not merely a consequence of cellular proliferation. Nucleotide sequence analysis identified pTB16 as the human counterpart for rat testicular sulfated glycoprotein 2 (SGP-2), whose function in the reproductive system remains unknown. Although SGP-2 transcripts, and hence pTB16, were recently shown to be increased in neurodegenerative diseases such as scrapie in hamsters and Alzheimer disease in humans, our observations with brain tumors and epilepsy are suggestive of a role for pTB16 in neuropathologies in general and support the hypothesis of its involvement in tissue remodeling and cell death. PMID:1924317

  1. Complementary synaptic distribution of enzymes responsible for synthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in the human hippocampus.

    PubMed

    Ludányi, A; Hu, S S-J; Yamazaki, M; Tanimura, A; Piomelli, D; Watanabe, M; Kano, M; Sakimura, K; Maglóczky, Z; Mackie, K; Freund, T F; Katona, I

    2011-02-01

    Clinical and experimental evidence demonstrates that endocannabinoids play either beneficial or adverse roles in many neurological and psychiatric disorders. Their medical significance may be best explained by the emerging concept that endocannabinoids are essential modulators of synaptic transmission throughout the central nervous system. However, the precise molecular architecture of the endocannabinoid signaling machinery in the human brain remains elusive. To address this issue, we investigated the synaptic distribution of metabolic enzymes for the most abundant endocannabinoid molecule, 2-arachidonoylglycerol (2-AG), in the postmortem human hippocampus. Immunostaining for diacylglycerol lipase-α (DGL-α), the main synthesizing enzyme of 2-AG, resulted in a laminar pattern corresponding to the termination zones of glutamatergic pathways. The highest density of DGL-α-immunostaining was observed in strata radiatum and oriens of the cornu ammonis and in the inner third of stratum moleculare of the dentate gyrus. At higher magnification, DGL-α-immunopositive puncta were distributed throughout the neuropil outlining the immunonegative main dendrites of pyramidal and granule cells. Electron microscopic analysis revealed that this pattern was due to the accumulation of DGL-α in dendritic spine heads. Similar DGL-α-immunostaining pattern was also found in hippocampi of wild-type, but not of DGL-α knockout mice. Using two independent antibodies developed against monoacylglycerol lipase (MGL), the predominant enzyme inactivating 2-AG, immunostaining also revealed a laminar and punctate staining pattern. However, as observed previously in rodent hippocampus, MGL was enriched in axon terminals instead of postsynaptic structures at the ultrastructural level. Taken together, these findings demonstrate the post- and presynaptic segregation of primary enzymes responsible for synthesis and elimination of 2-AG, respectively, in the human hippocampus. Thus, molecular

  2. 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

  3. A critical role of the human hippocampus in an electrophysiological measure of implicit memory.

    PubMed

    Addante, Richard James

    2015-04-01

    The hippocampus has traditionally been thought to be critical for conscious explicit memory but not necessary for unconscious implicit memory processing. In a recent study of a group of mild amnesia patients with evidence of MTL damage limited to the hippocampus, subjects were tested on a direct test of item recognition confidence while electroencephalogram (EEG) was acquired, and revealed intact measures of explicit memory from 400 to 600 ms (mid-frontal old-new effect, FN400). The current investigation re-analyzed this data to study event-related potentials (ERPs) of implicit memory, using a recently developed procedure that eliminated declarative memory differences. Prior ERP findings from this technique were first replicated in two independent matched control groups, which exhibited reliable implicit memory effects in posterior scalp regions from 400 to 600 ms, which were topographically dissociated from the explicit memory effects of familiarity. However, patients were found to be dramatically impaired in implicit memory effects relative to control subjects, as quantified by a reliable condition × group interaction. Several control analyses were conducted to consider alternative factors that could account for the results, including outliers, sample size, age, or contamination by explicit memory, and each of these factors was systematically ruled out. Results suggest that the hippocampus plays a fundamental role in aspects of memory processing that are beyond conscious awareness. The current findings therefore indicate that both memory systems of implicit and explicit memory may rely upon the same neural structures - but function in different physiological ways.

  4. A critical role of the human hippocampus in an electrophysiological measure of implicit memory

    PubMed Central

    Addante, Richard James

    2015-01-01

    The hippocampus has traditionally been thought to be critical for conscious explicit memory but not necessary for unconscious implicit memory processing. In a recent study of a group of mild amnesia patients with evidence of MTL damage limited to the hippocampus, subjects were tested on a direct test of item recognition confidence while electroencephalogram (EEG) was acquired, and revealed intact measures of explicit memory from 400–600ms (mid-frontal old-new effect, FN400). The current investigation re-analyzed this data to study event-related potentials (ERPs) of implicit memory, using a recently developed procedure that eliminated declarative memory differences. Prior ERP findings from this technique were first replicated in two independent matched control groups, which exhibited reliable implicit memory effects in posterior scalp regions from 400–600 msec, which were topographically dissociated from the explicit memory effects of familiarity. However, patients were found to be dramatically impaired in implicit memory effects relative to control subjects, as quantified by a reliable condition × group interaction. Several control analysis were conducted to consider alternative factors that could account for the results, including outliers, sample size, age, or contamination by explicit memory, and each of these factors were systematically ruled out. Results suggest that the hippocampus plays a fundamental role in aspects of memory processing that is beyond conscious awareness. The current findings therefore indicate that both memory systems of implicit and explicit memory may rely upon the same neural structures – but function in different physiological ways. PMID:25562828

  5. Dose response effects of dermally applied diethanolamine on neurogenesis in fetal mouse hippocampus and potential exposure of humans.

    PubMed

    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.

  6. Single-voxel (1)H spectroscopy in the human hippocampus at 3 T using the LASER sequence: characterization of neurochemical profile and reproducibility.

    PubMed

    Allaïli, Najib; Valabrègue, Romain; Auerbach, Edward J; Guillemot, Vincent; Yahia-Cherif, Lydia; Bardinet, Eric; Jabourian, Maritza; Fossati, Philippe; Lehéricy, Stéphane; Marjańska, Małgorzata

    2015-10-01

    The hippocampus is crucial for long-term episodic memory and learning. It undergoes structural change in aging and is sensitive to neurodegenerative and psychiatric diseases. MRS studies have seldom been performed in the hippocampus due to technical challenges. The reproducibility of MRS in the hippocampus has not been evaluated at 3 T. The purpose of the present study was to quantify the concentration of metabolites in a small voxel placed in the hippocampus and evaluate the reproducibility of the quantification. Spectra were measured in a 2.4 mL voxel placed in the left hippocampus covering the body and most of the tail of the structure in 10 healthy subjects across three different sessions and quantified using LCModel. High-quality spectra were obtained, which allowed a reliable quantification of 10 metabolites including glutamate and glutamine. Reproducibility of MRS was evaluated with coefficient of variation, standard errors of measurement, and intraclass correlation coefficients. All of these measures showed improvement with increased number of averages. Changes of less than 5% in concentration of N-acetylaspartate, choline-containing compounds, and total creatine and of less than 10% in concentration of myo-inositol and the sum of glutamate and glutamine can be confidently detected between two measurements in a group of 20 subjects. A reliable and reproducible neurochemical profile of the human hippocampus was obtained using MRS at 3 T in a small hippocampal volume. PMID:26282328

  7. 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

  8. [Transient epileptic amnesia].

    PubMed

    Muramatsu, Kazuhiro; Yoshizaki, Takahito

    2016-03-01

    Transient amnesia is one of common clinical phenomenon of epilepsy that are encountered by physicians. The amnestic attacks are often associated with persistent memory disturbances. Epilepsy is common among the elderly, with amnesia as a common symptom and convulsions relatively uncommon. Therefore, amnesia due to epilepsy can easily be misdiagnosed as dementia. The term 'transient epileptic amnesia (TEA)' was introduced in the early 1990s by Kapur, who highlighted that amnestic attacks caused by epilepsy can be similar to those occurring in 'transient global amnesia', but are distinguished by features brevity and recurrence. In 1998, Zeman et al. proposed diagnostic criteria for TEA.

  9. Alternate task inhibits single-neuron category-selective responses in the human hippocampus while preserving selectivity in the amygdala.

    PubMed

    Steinmetz, Peter N

    2009-02-01

    One fifth of neurons in the medial-temporal lobe of human epilepsy patients respond selectively to categories of images, such as faces or cars. Here we show that responses of hippocampal neurons are rapidly modified as subjects alternate (over 60 sec) between two tasks (1) identifying images from a category, or (2) playing a simple video game superimposed on the same images. Category-selective responses, present when a subject identifies categories, are eliminated when the subject shifts to playing the game for 87% of category-selective hippocampal neurons. By contrast, responses in the amygdala are present during both tasks for 72% of category-selective amygdalar neurons. These results suggest that attention to images is required to evoke selective responses from single neurons in the hippocampus, but is not required by neurons in the amygdala.

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

    PubMed

    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.

  11. 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.

  12. Neurturin, persephin, and artemin in the human pre- and full-term newborn and adult hippocampus and fascia dentata.

    PubMed

    Quartu, Marina; Serra, Maria Pina; Manca, Annalisa; Mascia, Francesca; Follesa, Paolo; Del Fiacco, Marina

    2005-04-18

    The immunochemical occurrence and localization of the Glial cell line-derived neurotrophic factor (GDNF) family ligands neurturin (NTN), persephin (PSP), and artemin (ART) is described in the human postmortem hippocampus and fascia dentata from subjects aged 21 weeks of gestation to 88 years. The detectability of NTN, PSP, and ART is shown in the rat by Western blot and immunohistochemistry up to 70 h postmortem. In the human tissue, labeled neuronal perikarya were detectable for each trophin at all examined ages, with prevalent localization in the pyramidal layer of the Ammon's horn and hilus and granular layer of the fascia dentata. In the adult subjects, punctate elements were also present. Comparison of the pattern of immunoreactive structures among young and adult subjects suggests that intracellular distribution and/or trafficking of the GDNF family ligands may undergo age-related changes. Labeled glial elements were also identifiable. Western blot analysis indicates that the availability of the dimeric and monomeric forms of the trophins may vary with age and postmortem delay. The results obtained suggest the involvement of NTN, PSP, and ART in processes subserving both the organization of this cortical region during development and the functional activity and maintenance of the mature human hippocampal neurons.

  13. The human hippocampus beyond the cognitive map: evidence from a densely amnesic patient

    PubMed Central

    Banta Lavenex, Pamela A.; Colombo, Françoise; Ribordy Lambert, Farfalla; Lavenex, Pierre

    2014-01-01

    We tested a densely amnesic patient (P9), with bilateral hippocampal damage resulting from an autoimmune disorder, and 12 age- and sex-matched controls on a series of memory tasks designed to characterize allocentric spatial learning and memory abilities. We compared P9's ability to perform spatial memory tasks with her ability to perform non-spatial, color memory tasks. First, P9's performance was impaired as compared to controls even in the simplest versions of an allocentric spatial memory task, in which she had to find repeatedly over 10 trials the same location(s) of one, two or three illuminating foot pad(s) among 23 pads distributed in an open-field arena. In contrast, she performed as well as controls when she had to find repeatedly over 10 trials the same one, two or three pad(s) marked by color cue(s), whose locations varied between trials. Second, P9's performance was severely impaired in working memory tasks, when she had to learn on a trial-unique basis and remember the location(s) or the color(s) of one, two or three pad(s), while performing an interfering task during the 1-min interval separating encoding and retrieval. Without interference during the retention interval of the trial-unique tasks, P9's performance was partially preserved in the color tasks, whereas it remained severely impaired in the allocentric spatial tasks. Detailed behavioral analyses indicate that P9's memory representations are more limited than those of controls both in their precision (metric coding) and in the number of items that can be maintained in memory (capacity). These findings are consistent with the theory that the hippocampus contributes to the integration or binding of multiple items, in order to produce high-resolution/high-capacity representations of spatial and non-spatial information in the service of short-term/working and long-term memory. PMID:25309387

  14. Yes/no recognition, forced-choice recognition, and the human hippocampus.

    PubMed

    Bayley, P J; Wixted, J T; Hopkins, R O; Squire, L R

    2008-03-01

    Two recent studies reported that yes/no recognition can be more impaired by hippocampal lesions than forced-choice recognition when the targets and foils are highly similar. This finding has been taken in support of two fundamental proposals: (1) yes/no recognition tests depend more on recollection than do forced-choice tests; and (2) the hippocampus selectively supports the recollection process. Using the same stimulus materials as in the earlier studies, we tested five memory-impaired patients with circumscribed hippocampal lesions and 15 controls. As in the earlier studies, participants studied 12 pictures of objects and then took either a 12-item forced-choice test with four alternatives or a 60-item yes/no test. Patients were impaired on both tests but did more poorly on the yes/no test. However, a yes/no test based on 12 study items would conventionally involve only 24 test items (i.e., 12 study items and 12 foil items). When we scored only the first 24 test items, the patients performed identically on the yes/no and forced-choice tests. Examination of the data in blocks of 12 trials indicated that the scores of the patients declined as testing continued. We suggest that a yes/no test of 60 items is difficult relative to a 12-item forced-choice test due to the increased study-test delay and due to increased interference, not because of any fundamental difference between the yes/no and forced-choice formats. We conclude that hippocampal lesions impair yes/no and forced-choice recognition to the same extent.

  15. 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.

  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.

  17. 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

  18. Morphological imaging of the hippocampus in epilepsy.

    PubMed

    Isnard, J; Bourdillon, P

    2015-03-01

    The hippocampus is a structure frequently involved in epilepsy, especially in partial drug-resistant forms. In addition, some hippocampal pathologies are associated with specific types of epilepsy presenting specific clinical courses and requiring specific treatments. Considering these major implications for treatment, morphological investigations of the hippocampus are crucial for epileptic patients. Indeed, discovery of hippocampal sclerosis may (depending on the clinical and electrophysiological findings) lead to the diagnosis of mesial temporal lobe epilepsy (MTLE). If the diagnosis of MTLE is retained in a case of drug-resistance, surgery may be proposed without invasive phase II investigations such as stereoelectroencephalograpy. In other instances, hippocampal abnormalities may be associated with epilepsy, but without the same value for localizing the ictal onset zone. Hippocampal dysgenesis is a strong argument for non-temporo-mesial ictal onset ipsilateral to the malformation. We describe here the specific MRI modalities adapted for hippocampal investigations and the radiological signs of hippocampal pathologies associated with epilepsy (especially hippocampal sclerosis and hippocamal dysgenesis). Hippocampus morphological investigations in epilepsy require specific MRI modalities and appropriate knowledge of the specific signs of each pathology. Careful analysis is crucial since the results may have a major impact on the therapeutic management of epileptic patients.

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

    PubMed

    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.

  20. 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

  1. The hippocampus: A central node in a large-scale brain network for memory.

    PubMed

    Huijgen, J; Samson, S

    2015-03-01

    The medial temporal lobe is a key region in the formation and consolidation of conscious or declarative memories. In this review, we will first consider the role of the hippocampus and its surrounding medial temporal lobe structures in recognition memory from a historical perspective. According to the dual process model of recognition memory, recognition judgments can be based on the recollection of details about previous presented stimuli or on the feeling of familiarity. Studies in humans, primates and rodents suggest that the hippocampus, the parahippocampal cortex and the perirhinal cortex play different roles in recollection and familiarity. Then, we will describe the role of the hippocampus and neocortex in memory consolidation: a process in which novel memories become integrated into long-term memory. After presenting possible mechanisms underlying sleep-dependent declarative memory consolidation, we will discuss the phenomenon of accelerated long-term forgetting. This type of memory deficit is often observed in epileptic patients with a hippocampal lesion, and provides a novel opportunity to investigate post-encoding and memory consolidation processes.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Human Neural Stem Cell Transplantation Provides Long-Term Restoration of Neuronal Plasticity in the Irradiated Hippocampus

    PubMed Central

    Acharya, Munjal M.; Rosi, Susanna; Jopson, Timothy; Limoli, Charles L.

    2016-01-01

    For the majority of CNS malignancies, radiotherapy provides the best option for forestalling tumor growth, but is frequently associated with debilitating and progressive cognitive dysfunction. Despite the recognition of this serious side effect, satisfactory long-term solutions are not currently available and have prompted our efforts to explore the potential therapeutic efficacy of cranial stem cell transplants. We have demonstrated that intrahippocampal transplantation of human neural stem cells (hNSCs) can provide long-lasting cognitive benefits using an athymic rat model subjected to cranial irradiation. To explore the possible mechanisms underlying the capability of engrafted cells to ameliorate radiation-induced cognitive dysfunction we analyzed the expression patterns of the behaviorally induced activity-regulated cytoskeleton-associated protein (Arc) in the hippocampus at 1 and 8 months postgrafting. While immunohistochemical analyses revealed a small fraction (4.5%) of surviving hNSCs in the irradiated brain that did not express neuronal or astroglial makers, hNSC transplantation impacted the irradiated microenvironment of the host brain by promoting the expression of Arc at both time points. Arc is known to play key roles in the neuronal mechanisms underlying long-term synaptic plasticity and memory and provides a reliable marker for detecting neurons that are actively engaged in spatial and contextual information processing associated with memory consolidation. Cranial irradiation significantly reduced the number of pyramidal (CA1) and granule neurons (DG) expressing behaviorally induced Arc at 1 and 8 months postirradiation. Transplantation of hNSCs restored the expression of plasticity-related Arc in the host brain to control levels. These findings suggest that hNSC transplantation promotes the long-term recovery of host hippocampal neurons and indicates that one mechanism promoting the preservation of cognition after irradiation involves trophic

  7. 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

  8. How sleep activates epileptic networks?

    PubMed

    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.

  9. 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

  10. Hsp60 response in experimental and human temporal lobe epilepsy.

    PubMed

    Marino Gammazza, Antonella; Colangeli, Roberto; Orban, Gergely; Pierucci, Massimo; Di Gennaro, Giancarlo; Lo Bello, Margherita; 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

    2015-03-24

    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.

  11. 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

  12. 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.

  13. 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.

  14. [Social adaptation of epileptic patients].

    PubMed

    Boldyrev, A I

    1983-01-01

    A comparative analysis of the changes seen in the field of social adaptation of epileptics over the last 21 years disclosed an increase in occupational adaptation of such patients in conditions of common production. Thus, judging by the number of epileptic patients registered in the outpatient psychoneurologic centers in 1958, 1970 and 1979, there has been a 8.8%-increase in the proportion of those being employed. Among the patients who work as office employees, some 45% are engaged in occupations requiring a definite unimpaired developmental and intellectual level. 80% of the affected children attend nonspecialized schools. All this necessitates the reviewing of the current concepts about the severity, course, and prognosis of epilepsy. A joint impact of biological and social factors is shown to be important in the occupational adaptation of patients. Considerable attention is given to the role of environmental, including psychogenic factors in the formation of secondary neurotic and psychic disorders. PMID:6880517

  15. [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

  16. 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

  17. 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

  18. Noisy neural nets exhibiting epileptic features.

    PubMed

    Kokkinidis, M; Anninos, P

    1985-04-01

    On the basis of our previous studies of noisy neural nets we propose a model for the explanation of epileptic phenomena. Our neural net model is capable of exhibiting epileptic features if the number of spontaneously firing neurons is periodically increased beyond a certain threshold. Some alternative epileptogenic mechanisms are also discussed. The epileptic behavior of the neural net is determined by a combination of certain parameters of its phase diagram. The general features of the model are consistent with several experimental observations and explain some poorly understood clinical phenomena. The differences between normal and epileptic neural nets are explained in terms of the structural properties of the model.

  19. Transient epileptic amnesia: a concise review.

    PubMed

    Asadi-Pooya, Ali A

    2014-02-01

    Transient epileptic amnesia (TEA) is a distinctive syndrome and comprises episodic transient amnesia with an epileptic basis, without impairment of other aspects of cognitive function. Additional interictal memory deficits are common in TEA. An epileptic origin, after other etiologies have been excluded, should be considered and carefully investigated in patients complaining of isolated memory disturbances, particularly with recurrent short-lasting amnesic attacks. In all suspected cases of epilepsy, a detailed clinical history is of paramount importance, but ancillary tests including EEG and MRI could be very helpful. Transient epileptic amnesia is typically a benign and treatable condition. Future studies should investigate the exact mechanism(s) of this unique syndrome.

  20. 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

  1. Expression of glutamatergic genes in healthy humans across 16 brain regions; altered expression in the hippocampus after chronic exposure to alcohol or cocaine.

    PubMed

    Enoch, M-A; Rosser, A A; Zhou, Z; Mash, D C; Yuan, Q; Goldman, D

    2014-11-01

    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

  2. Nutritional Aspects of Treatment in Epileptic Patients

    PubMed Central

    SOLTANI, Danesh; GHAFFAR POUR, Majid; TAFAKHORI, Abbas; SARRAF, Payam; BITARAFAN, Sama

    2016-01-01

    Epilepsy is a neurological disorder characterized by interruption of normal neuronal functions that is manifested by behavioral disorders, changing of awareness level, and presence of some sensory, autonomic and motor symptoms or signs. It is resulted from many different causes. Many antiepileptic drugs (AEDs) are considered to manage epileptic attacks. Some of them change metabolism and absorption of many nutrients. Therefore, epileptic patients may be in higher risk of nutrient deficiency and its unwelcome effects. In the present paper, we intend to review the relationship between nutrition and epilepsy in two aspects. In one aspect we discuss the nutritional status in epileptic patients, the causes of nutritional deficiencies and the way of compensation of the nutrient deficiencies. It will guide these patients to have a healthy life. In another aspect we explain the role of some nutrients and specific diets in management of epileptic attacks. It can help to better control of epileptic attacks in these patients. PMID:27375750

  3. [West syndrome associated with epileptic negative myoclonus].

    PubMed

    Shibata, Takashi; Yoshinaga, Harumi; Oka, Makio; Kobayashi, Katsuhiro

    2014-09-01

    We report a 10-month-old girl who had brief epileptic negative myoclonus during the course of West syndrome. She began to have epileptic spasms in series at the age of 8 months. Video-electroencephalograph (EEG) monitoring revealed that she also had brief epileptic negative myoclonus when she was 10 months old. Brief atonia of limbs occurred in isolation or in a cluster during drowsiness or sleep. The ictal EEG exhibited diffuse polyspikes and waves or diffuse high-voltage slow waves that were overlapped by low-voltage fast waves. 3 to 4 hundred milliseconds of silent periods were observed in the bilateral deltoid electromyograms, which correspond to the EEG patterns. The occurrence of other types of seizures, partial seizures in particular, accompanied by epileptic spasms has been fully investigated. This is the first case report of a patient with West syndrome whose coexisting epileptic negative myoclonus was confirmed by a silent electromyogram pattern.

  4. Mechanisms of physiological and epileptic HFO generation

    PubMed Central

    Jefferys, John G.R.; de la Prida, Liset Menendez; Wendling, Fabrice; Bragin, Anatol; Avoli, Massimo; Timofeev, Igor; Lopes da Silva, Fernando H.

    2016-01-01

    High frequency oscillations (HFO) have a variety of characteristics: band-limited or broad-band, transient burst-like phenomenon or steady-state. HFOs may be encountered under physiological or under pathological conditions (pHFO). Here we review the underlying mechanisms of oscillations, at the level of cells and networks, investigated in a variety of experimental in vitro and in vivo models. Diverse mechanisms are described, from intrinsic membrane oscillations to network processes involving different types of synaptic interactions, gap junctions and ephaptic coupling. HFOs with similar frequency ranges can differ considerably in their physiological mechanisms. The fact that in most cases the combination of intrinsic neuronal membrane oscillations and synaptic circuits are necessary to sustain network oscillations is emphasized. Evidence for pathological HFOs, particularly fast ripples, in experimental models of epilepsy and in human epileptic patients is scrutinized. The underlying mechanisms of fast ripples are examined both in the light of animal observations, in vivo and in vitro, and in epileptic patients, with emphasis on single cell dynamics. Experimental observations and computational modeling have led to hypotheses for these mechanisms, several of which are considered here, namely the role of out-of-phase firing in neuronal clusters, the importance of strong excitatory AMPA-synaptic currents and recurrent inhibitory connectivity in combination with the fast time scales of IPSPs, ephaptic coupling and the contribution of interneuronal coupling through gap junctions. The statistical behaviour of fast ripple events can provide useful information on the underlying mechanism and can help to further improve classification of the diverse forms of HFOs. PMID:22420980

  5. Long-term expression of human contextual fear and extinction memories involves amygdala, hippocampus and ventromedial prefrontal cortex: a reinstatement study in two independent samples.

    PubMed

    Lonsdorf, Tina B; Haaker, Jan; Kalisch, Raffael

    2014-12-01

    Human context conditioning studies have focused on acquisition and extinction. Subsequent long-term changes in fear behaviors not only depend on associative learning processes during those phases but also on memory consolidation processes and the later ability to retrieve and express fear and extinction memories. Clinical theories explain relapse after successful exposure-based treatment with return of fear memories and remission with stable extinction memory expression. We probed contextual fear and extinction memories 1 week (Day8) after conditioning (Day1) and subsequent extinction (Day2) by presenting conditioned contexts before (Test1) and after (Test2) a reinstatement manipulation. We find consistent activation patterns in two independent samples: activation of a subgenual part of the ventromedial prefrontal cortex before reinstatement (Test1) and (albeit with different temporal profiles between samples) of the amygdala after reinstatement (Test2) as well as up-regulation of anterior hippocampus activity after reinstatement (Test2 > Test1). These areas have earlier been implicated in the expression of cued extinction and fear memories. The present results suggest a general role for these structures in defining the balance between fear and extinction memories, independent of the conditioning mode. The results are discussed in the light of hypotheses implicating the anterior hippocampus in the processing of situational ambiguity.

  6. Progress in autoimmune epileptic encephalitis

    PubMed Central

    Wright, S.; Vincent, A.

    2016-01-01

    Purpose of review Autoimmune epileptic encephalopathy is a potentially treatable neurological syndrome characterized by the coexistence of a neuronal antibody in the CSF and serum. Patients present with combinations of seizures, neuropsychiatric features, movement disorder and cognitive decline, but some patients have isolated seizures either at first presentation or during their illness. This review summarises our current understanding of the roles of specific neuronal antibodies in epilepsy-related syndromes and aims to aid the clinician in diagnosis and treatment. Recent findings Antigen discovery methods in three neuroimmunology centres independently identified antibodies to different subunits of the GABAA receptor; high levels of these antibodies were found mainly in patients with severe refractory seizures. These and other antibodies were also found in a proportion (<10%) of children and adults with epilepsy. A clinical study comparing immunotherapy in patients with autoantibodies or without an identified target antigen found neuroinflammatory features were predictive of a therapeutic response. New in-vitro and in-vivo studies, and spontaneous animal models, have confirmed the pathogenicity and epileptogenicity of neuronal antibodies and their relevance to other mammals. Summary Neuronal antibodies are an important cause of autoimmune epileptic encephalopathy, early recognition is important as there may be an underlying tumour, and early treatment is associated with a better outcome. In the absence of an antibody, the clinician should adopt a pragmatic approach and consider a trial of immunotherapy when other causes have been excluded. PMID:26886357

  7. Hippocampus: cognitive processes and neural representations that underlie declarative memory.

    PubMed

    Eichenbaum, Howard

    2004-09-30

    The hippocampus serves a critical role in declarative memory--our capacity to recall everyday facts and events. Recent studies using functional brain imaging in humans and neuropsychological analyses of humans and animals with hippocampal damage have revealed some of the elemental cognitive processes mediated by the hippocampus. In addition, recent characterizations of neuronal firing patterns in behaving animals and humans have suggested how neural representations in the hippocampus underlie those elemental cognitive processes in the service of declarative memory.

  8. Ultra-high Resolution In-vivo 7.0T Structural Imaging of the Human Hippocampus Reveals the Endfolial Pathway

    PubMed Central

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

    2015-01-01

    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 unique neuroanatomy in humans compared to monkeys and rodents, with field CA3h greatly enlarged in humans compared to 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, balanced steady-state free precession (bSSFP) that can achieve 0.4 mm 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 0.1 mm 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

  9. 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

  10. Transient epileptic amnesia: Update on a slowly emerging epileptic syndrome.

    PubMed

    Felician, O; Tramoni, E; Bartolomei, F

    2015-03-01

    Transient epileptic amnesia (TEA) is a recently individualized, late-onset, pharmaco-sensitive form of mesial temporal lobe epilepsy with recurrent episodes of acute memory loss, but also interictal memory disturbances characterized by autobiographical and topographical memory impairment and a long-term consolidation deficit. In this article, we review the main clinical and electrophysiological characteristics of TEA, discuss its putative neuroanatomical substrate and mechanisms, common features and how it differs from related concepts, with the overall aim to defend the idea that TEA deserves to be recognized as a distinct epilepsy syndrome. While the pathophysiological basis remains largely unknown, emotional and/or dysimmune factors may have a potential influence. Most importantly, the concept of TEA is highly relevant to tertiary epilepsy and memory clinics, but also to routine neurology practice, leading to an adequate diagnosis and management of epilepsy-related, acute and long-standing memory deficits.

  11. Anti-epileptic effects of neuropeptide Y gene transfection into the rat brain☆

    PubMed Central

    Dong, Changzheng; Zhao, Wenqing; Li, Wenling; Lv, Peiyuan; Dong, Xiufang

    2013-01-01

    Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carrying the neuropeptide Y gene was transfected into brain tissue of rats with kainic acid-induced epilepsy through stereotactic methods. Following these transfections, we verified overexpression of the neuropeptide Y gene in the epileptic brain. Electroencephalograms showed that seizure severity was significantly inhibited and seizure latency was significantly prolonged up to 4 weeks after gene transfection. Moreover, quantitative fluorescent PCR and western blot assays revealed that the mRNA and protein expression of the N-methyl-D-aspartate receptor subunits NR1, NR2A, and NR2B was inhibited in the hippocampus of epileptic rats. These findings indicate that neuropeptide Y may inhibit seizures via down-regulation of the functional expression of N-methyl-D-aspartate receptors. PMID:25206425

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. Variable telomere length across post-mortem human brain regions and specific reduction in the hippocampus of major depressive disorder.

    PubMed

    Mamdani, F; Rollins, B; Morgan, L; Myers, R M; Barchas, J D; Schatzberg, A F; Watson, S J; Akil, H; Potkin, S G; Bunney, W E; Vawter, M P; Sequeira, P A

    2015-09-15

    Stress can be a predisposing factor to psychiatric disorders and has been associated with decreased neurogenesis and reduced hippocampal volume especially in depression. Similarly, in white blood cells chronic psychological stress has been associated with telomere shortening and with mood disorders and schizophrenia (SZ). However, in previous post-mortem brain studies from occipital cortex and cerebellum, no difference in telomere length was observed in depression. We hypothesized that in psychiatric disorders, stress-driven accelerated cellular aging can be observed in brain regions particularly sensitive to stress. Telomere length was measured by quantitative-PCR in five brain regions (dorsolateral prefrontal cortex, hippocampus (HIPP), amygdala, nucleus accumbens and substantia nigra (SN)) in major depressive disorder (MDD), bipolar disorder, SZ and normal control subjects (N = 40, 10 subjects per group). We observed significant differences in telomere length across brain regions suggesting variable levels of cell aging, with SN and HIPP having the longest telomeres and the dorsolateral prefrontal cortex the shortest. A significant decrease (P < 0.02) in telomere length was observed specifically in the HIPP of MDD subjects even after controlling for age. In the HIPP of MDD subjects, several genes involved in neuroprotection and in stress response (FKBP5, CRH) showed altered levels of mRNA. Our results suggest the presence of hippocampal stress-mediated accelerated cellular aging in depression. Further studies are needed to investigate the cellular specificity of these findings.

  18. Variable telomere length across post-mortem human brain regions and specific reduction in the hippocampus of major depressive disorder

    PubMed Central

    Mamdani, F; Rollins, B; Morgan, L; Myers, R M; Barchas, J D; Schatzberg, A F; Watson, S J; Akil, H; Potkin, S G; Bunney, W E; Vawter, M P; Sequeira, P A

    2015-01-01

    Stress can be a predisposing factor to psychiatric disorders and has been associated with decreased neurogenesis and reduced hippocampal volume especially in depression. Similarly, in white blood cells chronic psychological stress has been associated with telomere shortening and with mood disorders and schizophrenia (SZ). However, in previous post-mortem brain studies from occipital cortex and cerebellum, no difference in telomere length was observed in depression. We hypothesized that in psychiatric disorders, stress-driven accelerated cellular aging can be observed in brain regions particularly sensitive to stress. Telomere length was measured by quantitative-PCR in five brain regions (dorsolateral prefrontal cortex, hippocampus (HIPP), amygdala, nucleus accumbens and substantia nigra (SN)) in major depressive disorder (MDD), bipolar disorder, SZ and normal control subjects (N=40, 10 subjects per group). We observed significant differences in telomere length across brain regions suggesting variable levels of cell aging, with SN and HIPP having the longest telomeres and the dorsolateral prefrontal cortex the shortest. A significant decrease (P<0.02) in telomere length was observed specifically in the HIPP of MDD subjects even after controlling for age. In the HIPP of MDD subjects, several genes involved in neuroprotection and in stress response (FKBP5, CRH) showed altered levels of mRNA. Our results suggest the presence of hippocampal stress-mediated accelerated cellular aging in depression. Further studies are needed to investigate the cellular specificity of these findings. PMID:26371764

  19. STATUS EPILEPTICUS TRIGGERS EARLY AND LATE ALTERATIONS IN BRAIN-DERIVED NEUROTROPHIC FACTOR AND NMDA GLUTAMATE RECEPTOR GRIN2B DNA METHYLATION LEVELS IN THE HIPPOCAMPUS

    PubMed Central

    Parrish, R. Ryley; Albertson, Asher J.; Buckingham, Susan C.; Hablitz, John J.; Mascia, Katherine L.; Haselden, W. Davis; Lubin, Farah D.

    2013-01-01

    Status epilepticus (SE) triggers abnormal expression of genes in the hippocampus, such as glutamate receptor subunit epsilon-2 (Grin2b/Nr2b) and brain-derived neurotrophic factor (Bdnf), that is thought to occur in temporal lobe epilepsy (TLE). We examined the underlying DNA methylation mechanisms and investigated whether these mechanisms contribute to the expression of these gene targets in the epileptic hippocampus. Experimental TLE was provoked by kainic acid-induced SE. Bisulfite sequencing analysis revealed increased Grin2b/Nr2b and decreased Bdnf DNA methylation levels that corresponded to decreased Grin2b/Nr2b and increased Bdnf mRNA and protein expression in the epileptic hippocampus. Blockade of DNA methyltransferase (DNMT) activity with zebularine decreased global DNA methylation levels and reduced Grin2b/Nr2b, but not Bdnf, DNA methylation levels. Interestingly, we found that DNMT blockade further decreased Grin2b/Nr2b mRNA expression whereas GRIN2B protein expression increased in the epileptic hippocampus, suggesting that a posttranscriptional mechanism may be involved. Using chromatin immunoprecipitation analysis we found that DNMT inhibition restored the decreases in AP2alpha transcription factor levels at the Grin2b/Nr2b promoter in the epileptic hippocampus. DNMT inhibition increased field excitatory postsynaptic potential in hippocampal slices isolated from epileptic rats. EEG monitoring confirmed that DNMT inhibition did not significantly alter disease course, but promoted the latency to seizure onset or SE. Thus, DNA methylation may be an early event triggered by SE that persists late into the epileptic hippocampus to contribute to gene expression changes in TLE. PMID:23811393

  20. 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

  1. Hippocampus: remembering the choices.

    PubMed

    Eichenbaum, Howard

    2013-03-20

    The hippocampus is said to be involved in "navigation" and "memory" as if these were distinct functions. In this issue of Neuron, Singer et al. (2013) provide evidence that the hippocampus retrieves spatial sequences in support of memory, strengthening a convergence between the two perspectives on hippocampal function.

  2. Hippocampus at 25.

    PubMed

    Eichenbaum, Howard; Amaral, David G; Buffalo, Elizabeth A; Buzsáki, György; Cohen, Neal; Davachi, Lila; Frank, Loren; Heckers, Stephan; Morris, Richard G M; Moser, Edvard I; Nadel, Lynn; O'Keefe, John; Preston, Alison; Ranganath, Charan; Silva, Alcino; Witter, Menno

    2016-10-01

    The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. © 2016 Wiley Periodicals, Inc.

  3. Hippocampus at 25.

    PubMed

    Eichenbaum, Howard; Amaral, David G; Buffalo, Elizabeth A; Buzsáki, György; Cohen, Neal; Davachi, Lila; Frank, Loren; Heckers, Stephan; Morris, Richard G M; Moser, Edvard I; Nadel, Lynn; O'Keefe, John; Preston, Alison; Ranganath, Charan; Silva, Alcino; Witter, Menno

    2016-10-01

    The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. © 2016 Wiley Periodicals, Inc. PMID:27399159

  4. Seizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatment.

    PubMed

    Pontes, Josy Carolina C; Lima, Thiago Z; Queiroz, Claudio M; Cinini, Simone M; Blanco, Miriam M; Mello, Luiz E

    2016-10-01

    The efficiency of most of the new antiepileptic drugs (AEDs) on clinical trials still falls short the success reported in pre-clinical studies, possibly because the validity of the animal models is insufficient to fully represent the human pathology. To improve the translational value for testing AEDs, we propose the use of non-human primates. Here, we suggest that triggering limbic seizures with low doses of PTZ in pilocarpine-treated marmosets might provide a more effective basis for the development of AED. Marmosets with epileptic background were more susceptible to seizures induced by PTZ, which were at least 3 times longer and more severe (about 6 times greater frequency of generalized seizures) in comparison to naïve peers. Accordingly, PTZ-induced seizures were remarkably less attenuated by AEDs in epileptic than naïve marmosets. While phenobarbital (40mg/kg) virtually abolished seizures regardless of the animal's background, carbamazepine (120mg/kg) and valproic acid (400mg/kg) could not prevent PTZ-induced seizures in epileptic animals with the same efficiency as observed in naïve peers. VPA was less effective regarding the duration of individual seizures in epileptic animals, as assessed in ECoG (p=0.05). Similarly following CBZ treatment, the behavioral manifestation of generalized seizures lasted longer in epileptic (p<0.05), which were also more frequent than in the naïve group (p<0.05). As expected, epileptic marmosets experiencing stronger seizures showed more NPY- and ΔFosB-immunostained neurons in a number of brain areas associated with the generation and spread of limbic seizures. Our results suggest that PTZ induced seizures over an already existing epileptic background constitutes a reliable and controllable mean for the screening of new AEDs.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. Chewing Maintains Hippocampus-Dependent Cognitive Function.

    PubMed

    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.

  13. Epileptic seizure induced by fennel essential oil.

    PubMed

    Skalli, Souad; Soulaymani Bencheikh, Rachida

    2011-09-01

    An epileptic seizure is reported in a 38-year-old woman, known to be an epileptic patient. Although she was under antiepileptic treatment and had well-controlled epilepsy, she developed a typical generalised tonic-clonic seizure and remained unconscious for 45 minutes following ingestion of a number of cakes containing an unknown quantity of fennel essential oil. Involuntary diarrhoea accompanied her epileptic seizure. This reported case recalls the fact that fennel essential oil can induce seizures and that this oil should probably be avoided by patients with epilepsy. Labelling of products with fennel essential oil should refer to the risk of seizures, particularly for patients with epilepsy. An awareness programme should involve all stakeholders affected by this issue.

  14. 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

  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. The Hippocampus as a Cognitive Map … of Social Space.

    PubMed

    Eichenbaum, Howard

    2015-07-01

    The traditional view of the hippocampus is that it creates a cognitive map to navigate physical space. Here, in this issue of Neuron, Tavares et al. (2015) show that the human hippocampus maps dimensions of social space, indicating a function in the service of navigating everyday life.

  17. 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…

  18. 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…

  19. Magnetoencephalography in pediatric neurology and in epileptic syndromes.

    PubMed

    Verrotti, Alberto; Pizzella, Vittorio; Trotta, Daniela; Madonna, Laura; Chiarelli, Francesco; Romani, Gian Luca

    2003-04-01

    In recent years, great advances in the knowledge of neuromagnetism have permitted the application of Superconducting Quantum Interference Devices to the pathophysiologic study of the human brain. In particular, in pediatric neurology, the integration of biomagnetism with magnetic resonance imaging and other techniques for medical imaging have allowed for precise neuromagnetic measurements of the human brain. The more frequently used technique is magnetoencephalography. Recent data have illustrated the usefulness of magnetoencephalography in mapping activity of sensory and motor areas and in studying the spatiotemporal pattern of brain activation specific to somatosensory function. Moreover, magnetoencephalography is an important tool to localize epileptic activity; magnetic source imaging superimposes magnetoencephalographic localizations on the magnetic resonance imaging and yields improved spatial resolution as compared with surface electroencephalography. The role of magnetoencephalography in evaluating patients with epilepsy continues to evolve; in fact, it seems to be very useful in the localization of the epileptogenic zone in patients with partial epilepsy. This application of magnetoencephalography is essential in the selection of epileptic children candidates to surgical treatment of seizures.

  20. [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.

  1. 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

  2. "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].

  3. Mapping Epileptic Activity: Sources or Networks for the Clinicians?

    PubMed Central

    Pittau, Francesca; Mégevand, Pierre; Sheybani, Laurent; Abela, Eugenio; Grouiller, Frédéric; Spinelli, Laurent; Michel, Christoph M.; Seeck, Margitta; Vulliemoz, Serge

    2014-01-01

    Epileptic seizures of focal origin are classically considered to arise from a focal epileptogenic zone and then spread to other brain regions. This is a key concept for semiological electro-clinical correlations, localization of relevant structural lesions, and selection of patients for epilepsy surgery. Recent development in neuro-imaging and electro-physiology and combinations, thereof, have been validated as contributory tools for focus localization. In parallel, these techniques have revealed that widespread networks of brain regions, rather than a single epileptogenic region, are implicated in focal epileptic activity. Sophisticated multimodal imaging and analysis strategies of brain connectivity patterns have been developed to characterize the spatio-temporal relationships within these networks by combining the strength of both techniques to optimize spatial and temporal resolution with whole-brain coverage and directional connectivity. In this paper, we review the potential clinical contribution of these functional mapping techniques as well as invasive electrophysiology in human beings and animal models for characterizing network connectivity. PMID:25414692

  4. 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

  5. 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

  6. The anticonvulsant and neuroprotective effects of baicalin on pilocarpine-induced epileptic model in rats.

    PubMed

    Liu, Yang-Feng; Gao, Fei; Li, Xiao-Wei; Jia, Rui-Hua; Meng, Xian-Dong; Zhao, Rui; Jing, Yun-Yun; Wang, Ying; Jiang, Wen

    2012-08-01

    Baicalin, a flavonoid compound purified from plant Scutellaria baicalensis Georgi, has been reported to possess a wide variety of pharmacological properties including anti-oxidative, anti-apoptotic and neuroprotective properties. Oxidative stress can dramatically alter neuronal function and has been linked to status epilepticus (SE). However, the neuroprotective effect of baicalin on epilepsy is unclear. In this study we investigated whether Baicalin could exert anticonvulsant and neuroprotective effects in the pilocarpine-induced epileptic model in rats. To this end, we recorded the latency to first limbic seizure and SE and observed the incidence of SE and mortality. The changes of oxidative stress were measured 24 h after pilocarpine-induced SE. Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Fluoro-Jade B staining were performed to detect the neuronal loss, apoptosis and degeneration in hippocampus 72 h after pilocarpine-induced seizure. Pretreatment with baicalin significantly delayed the onset of the first limbic seizures and SE, reduced the mortality rate, and attenuated the changes in the levels of lipid peroxidation, nitrite content and reduced glutathione in the hippocampus of pilocarpine-treated rats. Furthermore, we also found that baicalin attenuated the neuronal cell loss, apoptosis, and degeneration caused by pilocarpine-induced seizures in rat hippocampus. Collectively, these results indicated remarkable anticonvulsant and neuroprotective effects of baicalin and should encourage further studies to investigate baicalin as an adjuvant in epilepsy both to prevent seizures and to protect against seizure induced brain injury.

  7. 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.

  8. [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

  9. 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.

  10. 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

  11. Pattern separation in the hippocampus

    PubMed Central

    Yassa, Michael A.; Stark, Craig E. L.

    2011-01-01

    The ability to discriminate among similar experiences is a critical feature of episodic memory. This ability has long been hypothesized to require the hippocampus, with computational models suggesting it is dependent on pattern separation. However, empirical data for the hippocampus’ role in pattern separation was not available until recently. This review summarizes data from electrophysiological recordings, lesion studies, immediate early gene imaging, transgenic mouse models, as well as human functional neuroimaging that provide convergent evidence for the involvement of particular hippocampal subfields in this key process. We discuss the impact of aging and adult neurogenesis on pattern separation, as well as highlight several challenges to linking across species and approaches and suggest future directions for investigation. PMID:21788086

  12. 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

  13. 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

  14. 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.

  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.

  17. 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

  18. [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

  19. Complex partial epileptic-like experiences in university students and practitioners of Dharmakaya in Thailand: comparison with Canadian university students.

    PubMed

    Murphy, T; Persinger, M A

    2001-08-01

    We tested the hypothesis that individuals who frequently practice meditation within another culture whose assumptions explicitly endorse this practice should exhibit more frequent and varied experience associated with complex partial epilepsy (without the seizures) as inferred by the Personal Philosophy Inventory and Roberts' Questionnaire for the Epileptic Spectrum Disorder. 80 practitioners of Dharma Meditation and 24 university students in Thailand were compared with 76 students from first-year courses in psychology in a Canadian university. Although there were large significant differences for some items and clusters of items expected as a result of cultural differences, there were no statistically significant differences between the two populations for the proportions of complex partial epileptic-like experiences or their frequency of occurrence. There were no strong or consistent correlations between the history of meditation within the sample who practiced Dharma meditation and these experiences. These results suggest complex partial epileptic-like experiences may be a normal feature of the human species.

  20. 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.

  1. 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.

  2. Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

    PubMed Central

    Liu, Chung-Hsiang; Lin, Yi-Wen; Tang, Nou-Ying; Liu, Hsu-Jan; Hsieh, Ching-Liang

    2012-01-01

    Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus PMID:21837247

  3. Thrombin induces long-term potentiation of reactivity to afferent stimulation and facilitates epileptic seizures in rat hippocampal slices: toward understanding the functional consequences of cerebrovascular insults.

    PubMed

    Maggio, Nicola; Shavit, Efrat; Chapman, Joab; Segal, Menahem

    2008-01-16

    The effects of thrombin, a blood coagulation serine protease, were studied in rat hippocampal slices, in an attempt to comprehend its devastating effects when released into the brain after stroke and head trauma. Thrombin acting through its receptor, protease-activated receptor 1 (PAR1), produced a long-lasting enhancement of the reactivity of CA1 neurons to afferent stimulation, an effect that saturated the ability of the tissue to undergo tetanus-induced long-term potentiation. This effect was mediated by activation of a PAR1 receptor, because it was shared by a PAR1 agonist, and was blocked by its selective antagonist. An independent effect of thrombin involved the lowering of the threshold for generating epileptic seizures in CA3 region of the hippocampus. Thus, the experiments in a slice mimicked epileptic and cognitive dysfunction induced by thrombin in the brain, and suggest that these effects are mediated by activation of the PAR1 receptor. PMID:18199772

  4. 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.

  5. 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

  6. Distribution entropy analysis of epileptic EEG signals.

    PubMed

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

    2015-01-01

    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. Alterations in serotonin receptors and transporter immunoreactivities in the hippocampus in the rat unilateral hypoxic-induced epilepsy model.

    PubMed

    An, Sung-Jin; Kim, Duk-Soo

    2011-11-01

    Unilateral hypoxic-ischemia results in the frequent occurrence of interictal spikes, and occasionally sustained ictal discharges accompanied by a reduction in paired-pulse inhibition within the non-lesioned dentate gyrus. To elucidate the roles of serotonin (5-hydroxytryptamine [5-HT]) in an epileptogenic insult, we investigated the changes in 5-HT receptors and serotonin transporter (5-HTT) immunoreactivities within the lesioned and contralateral hippocampus following unilateral hypoxic-ischemia. During epileptogenic periods following hypoxic-ischemia, both 5-HT(1A) and 5HT(1B) receptor immunoreactivities were decreased within the lesioned and the non-lesioned hippocampus. However, 5-HTT immunoreactivity was transiently increased within the hippocampus bilaterally. These findings indicate that alteration of the 5-HT system results in a "diaschisis" pattern, and may contribute to neuronal death and the development of emotional disorders in epileptic patients accompanied by psychological stress.

  8. Chronic Dysfunction of Astrocytic Inwardly Rectifying K+ Channels Specific to the Neocortical Epileptic Focus After Fluid Percussion Injury in the Rat

    PubMed Central

    Stewart, Tessandra H.; Eastman, Clifford L.; Groblewski, Peter A.; Fender, Jason S.; Verley, Derek R.; Cook, David G.

    2010-01-01

    Astrocytic inwardly rectifying K+ currents (IKIR) have an important role in extracellular K+ homeostasis, which influences neuronal excitability, and serum extravasation has been linked to impaired KIR-mediated K+ buffering and chronic hyperexcitability. Head injury induces acute impairment in astroglial membrane IKIR and impaired K+ buffering in the rat hippocampus, but chronic spontaneous seizures appear in the perilesional neocortex—not the hippocampus—in the early weeks to months after injury. Thus we examined astrocytic KIR channel pathophysiology in both neocortex and hippocampus after rostral parasaggital fluid percussion injury (rpFPI). rpFPI induced greater acute serum extravasation and metabolic impairment in the perilesional neocortex than in the underlying hippocampus, and in situ whole cell recordings showed a greater acute loss of astrocytic IKIR in neocortex than hippocampus. IKIR loss persisted through 1 mo after injury only in the neocortical epileptic focus, but fully recovered in the hippocampus that did not generate chronic seizures. Neocortical cell-attached recordings showed no loss or an increase of IKIR in astrocytic somata. Confocal imaging showed depletion of KIR4.1 immunoreactivity especially in processes—not somata—of neocortical astrocytes, whereas hippocampal astrocytes appeared normal. In naïve animals, intracortical infusion of serum, devoid of coagulation-mediating thrombin activity, reproduces the effects of rpFPI both in vivo and at the cellular level. In vivo serum infusion induces partial seizures similar to those induced by rpFPI, whereas bath-applied serum, but not dialyzed albumin, rapidly silenced astrocytic KIR membrane currents in whole cell and cell-attached patch-clamp recordings in situ. Thus both acute impairment in astrocytic IKIR and chronic spontaneous seizures typical of rpFPI are reproduced by serum extravasation, whereas the chronic impairment in astroglial IKIR is specific to the neocortex that develops

  9. [Fever-induced refractory epileptic encephalopathy of children].

    PubMed

    Sivkova, S N; Bogdanov, E I; Zaĭkova, F M; Morozova, E A; Aiupova, V A; Zabbarova, A T; Shaĭmardanova, R M

    2013-01-01

    Fever-induced refractory epileptic encephalopathy of school-age children is a rare epileptic syndrome that causes difficulties in diagnosis at the initial stage of disease. It is characterized by sudden onset with multifocal refractory status epilepticus in previously healthy children with normal development. Later, children suffer from resistant focal epilepsy in the combination with cognitive deficit and behavioral difficulties. Authors describe a clinical case of fever-induced refractory epileptic encephalopathy of school-age children in a child of 7 years old. Aspects of etiology, pathogenesis, clinical manifestation, differential diagnosis, treatment and prognosis of the disease are discussed.

  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. [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

  12. [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.

  13. [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

  14. The hippocampus and visual perception

    PubMed Central

    Lee, Andy C. H.; Yeung, Lok-Kin; Barense, Morgan D.

    2012-01-01

    In this review, we will discuss the idea that the hippocampus may be involved in both memory and perception, contrary to theories that posit functional and neuroanatomical segregation of these processes. This suggestion is based on a number of recent neuropsychological and functional neuroimaging studies that have demonstrated that the hippocampus is involved in the visual discrimination of complex spatial scene stimuli. We argue that these findings cannot be explained by long-term memory or working memory processing or, in the case of patient findings, dysfunction beyond the medial temporal lobe (MTL). Instead, these studies point toward a role for the hippocampus in higher-order spatial perception. We suggest that the hippocampus processes complex conjunctions of spatial features, and that it may be more appropriate to consider the representations for which this structure is critical, rather than the cognitive processes that it mediates. PMID:22529794

  15. [Employment of epileptic patients abroad and their fitness for travel].

    PubMed

    Wendt, U

    1987-09-01

    On the basis of relevant literature and from personal experience, the paper discusses problems of the fitness of epileptics to travel by air and to work and holiday abroad. As an aid to consultation, tentative recommendations are made.

  16. 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

  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. 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

  19. 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

  20. 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

  1. The expression of somatostatin receptors in the hippocampus of pilocarpine-induced rat epilepsy model.

    PubMed

    Kwak, Sung-Eun; Kim, Ji-Eun; Choi, Hui-Chul; Song, Hong-Ki; Kim, Yeong-In; Jo, Seung-Mook; Kang, Tae-Cheon

    2008-01-01

    During the course of this study, we sought examine whether the expression of somatostatin receptors (SSTRs) is altered in the hippocampus following pilocarpine-induced status epilepticus (SE) in order to understand the role/function of SSTRs in the hippocampus after epileptogenic insults. SSTR1 and SSTR4 immunoreactivities were increased in the hippocampus at 1 week after SE. At 4 weeks after SE, SRIF1-family (SSTR 2A, SSTR2B, and SSTR5) immunoreactivity was increased only in neuropil. Both SSTR2A and 2B immunoreactivities were increased in CA2-3 pyramidal cells. However, SSTR3 and SSTR4 immunoreactivities were reduced in the CA1 pyramidal cells of epileptic rat due to neuronal loss. In addition, SSTR5 immunoreactivity was reduced in CA2 pyramidal cells and various interneurons. Both SSTR2B and SSTR4 immunoreactivities were increased within microglia following SE. Our findings suggest that increases in neuron-glial SSTR expressions may be closely related to the enhanced inhibition of the dentate gyrus and regulation of reactive microgliosis in the hippocampus of a pilocarpine model of temporal lobe epilepsy.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. Impaired expression and function of group II metabotropic glutamate receptors in pilocarpine-treated chronically epileptic rats

    PubMed Central

    Garrido-Sanabria, Emilio R.; Otalora, Luis F. Pacheco; Arshadmansab, Massoud F.; Herrera, Berenice; Francisco, Sebastian; Ermolinsky, Boris

    2008-01-01

    Group II metabotropic (mGlu II) receptor subtypes mGlu2 and mGlu3 are important modulators of synaptic plasticity and glutamate release in the brain. Accordingly, several pharmacological ligands have been designed to target these receptors for the treatment of neurological disorders characterized by anomalous glutamate regulation including epilepsy. In this study, we examine whether the expression level and function of mGlu2 and mGlu3 are altered in experimental epilepsy by using immunohistochemistry, Western blot analysis, RT-PCR and extracellular recordings. A down-regulation of mGlu2/3 protein expression at the mossy fiber pathway was associated with a significant reduction in mGlu2/3 protein expression in the hippocampus and cortex of chronically epileptic rats. Moreover, a reduction in mGlu2 and mGlu3 transcripts levels was noticed as early as 24h after pilocarpine-induced status epilepticus (SE) and persisted during subsequent “latent” and chronic periods. In addition, a significant impairment of mGlu II-mediated depression of field excitatory postsynaptic potentials at mossy fiber-CA3 synapses was detected in chronically epileptic rats. Application of mGlu II agonists (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) induced a significant reduction of the fEPSP amplitude in control rats, but not in chronic epileptic rats. These data indicate a long-lasting impairment of mGlu2/3 expression that may contribute to abnormal presynaptic plasticity, exaggerate glutamate release and hyperexcitability in temporal lobe epilepsy. PMID:18804094

  11. Impaired expression and function of group II metabotropic glutamate receptors in pilocarpine-treated chronically epileptic rats.

    PubMed

    Garrido-Sanabria, Emilio R; Otalora, Luis F Pacheco; Arshadmansab, Massoud F; Herrera, Berenice; Francisco, Sebastian; Ermolinsky, Boris S

    2008-11-13

    Group II metabotropic (mGlu II) receptor subtypes mGlu2 and mGlu3 are important modulators of synaptic plasticity and glutamate release in the brain. Accordingly, several pharmacological ligands have been designed to target these receptors for the treatment of neurological disorders characterized by anomalous glutamate regulation including epilepsy. In this study, we examine whether the expression level and function of mGlu2 and mGlu3 are altered in experimental epilepsy by using immunohistochemistry, Western blot analysis, RT-PCR and extracellular recordings. A down-regulation of mGlu2/3 protein expression at the mossy fiber pathway was associated with a significant reduction in mGlu2/3 protein expression in the hippocampus and cortex of chronically epileptic rats. Moreover, a reduction in mGlu2 and mGlu3 transcripts levels was noticed as early as 24 h after pilocarpine-induced status epilepticus (SE) and persisted during subsequent "latent" and chronic periods. In addition, a significant impairment of mGlu II-mediated depression of field excitatory postsynaptic potentials at mossy fiber-CA3 synapses was detected in chronically epileptic rats. Application of mGlu II agonists (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) induced a significant reduction of the fEPSP amplitude in control rats, but not in chronic epileptic rats. These data indicate a long-lasting impairment of mGlu2/3 expression that may contribute to abnormal presynaptic plasticity, exaggerate glutamate release and hyperexcitability in temporal lobe epilepsy. PMID:18804094

  12. [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.

  13. 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.

  14. 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.

  15. Getting directions from the hippocampus: The neural connection between looking and memory.

    PubMed

    Meister, Miriam L R; Buffalo, Elizabeth A

    2016-10-01

    Investigations into the neural basis of memory in human and non-human primates have focused on the hippocampus and associated medial temporal lobe (MTL) structures. However, how memory signals from the hippocampus affect motor actions is unknown. We propose that approaching this question through eye movement, especially by assessing the changes in looking behavior that occur with experience, is a promising method for exposing neural computations within the hippocampus. Here, we review how looking behavior is guided by memory in several ways, some of which have been shown to depend on the hippocampus, and how hippocampal neural signals are modulated by eye movements. Taken together, these findings highlight the need for future research on how MTL structures interact with the oculomotor system. Probing how the hippocampus reflects and impacts motor output during looking behavior renders a practical path to advance our understanding of the hippocampal memory system.

  16. 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…

  17. Seasonal change in the avian hippocampus.

    PubMed

    Sherry, David F; MacDougall-Shackleton, Scott A

    2015-04-01

    The hippocampus plays an important role in cognitive processes, including memory and spatial orientation, in birds. The hippocampus undergoes seasonal change in food-storing birds and brood parasites, there are changes in the hippocampus during breeding, and further changes occur in some species in association with migration. In food-storing birds, seasonal change in the hippocampus occurs in fall and winter when the cognitively demanding behaviour of caching and retrieving food occurs. The timing of annual change in the hippocampus of food-storing birds is quite variable, however, and appears not to be under photoperiod control. A variety of factors, including cognitive performance, exercise, and stress may all influence seasonal change in the avian hippocampus. The causal processes underlying seasonal change in the avian hippocampus have not been extensively examined and the more fully described hormonal influences on the mammalian hippocampus may provide hypotheses for investigating the control of hippocampal seasonality in birds.

  18. Impairment of GABA release in the hippocampus at the time of the first spontaneous seizure in the pilocarpine model of temporal lobe epilepsy.

    PubMed

    Soukupová, Marie; Binaschi, Anna; Falcicchia, Chiara; Zucchini, Silvia; Roncon, Paolo; Palma, Eleonora; Magri, Eros; Grandi, Enrico; Simonato, Michele

    2014-07-01

    The alterations in GABA release have not yet been systematically measured along the natural course of temporal lobe epilepsy. In this work, we analyzed GABA extracellular concentrations (using in vivo microdialysis under basal and high K(+)-evoked conditions) and loss of two GABA interneuron populations (parvalbumin and somatostatin neurons) in the ventral hippocampus at different time-points after pilocarpine-induced status epilepticus in the rat, i.e. during development and progression of epilepsy. We found that (i) during the latent period between the epileptogenic insult, status epilepticus, and the first spontaneous seizure, basal GABA outflow was reduced to about one third of control values while the number of parvalbumin-positive cells was reduced by about 50% and that of somatostatin-positive cells by about 25%; nonetheless, high K(+) stimulation increased extracellular GABA in a proportionally greater manner during latency than under control conditions; (ii) at the time of the first spontaneous seizure (i.e., when the diagnosis of epilepsy is made in humans) this increased responsiveness to stimulation disappeared, i.e. there was no longer any compensation for GABA cell loss; (iii) thereafter, this dysfunction remained constant until a late phase of the disease. These data suggest that a GABAergic hyper-responsiveness can compensate for GABA cell loss and protect from occurrence of seizures during latency, whereas impaired extracellular GABA levels can favor the occurrence of spontaneous recurrent seizures and the maintenance of an epileptic state.

  19. 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.

  20. Epileptic EEG visualization and sonification based on linear discriminate analysis.

    PubMed

    Wei Chen; Chia-Ping Shen; Ming-Jang Chiu; Qibin Zhao; Cichocki, Andrzej; Jeng-Wei Lin; Feipei Lai

    2015-08-01

    In this paper, we first presents a high accuracy epileptic electroencephalogram (EEG) classification algorithm. EEG data of epilepsy patients are preprocessed, segmented, and decomposed to intrinsic mode functions, from which features are extracted. Two classifiers are trained based on linear discriminant analysis (LDA) to classify EEG data into three types, i.e., normal, spike, and seizure. We further in-depth investigate the changes of the decision values in LDA on continuous EEG data. An epileptic EEG visualization and sonification algorithm is proposed to provide both temporal and spatial information of spike and seizure of epilepsy patients. In the experiment, EEG data of six subjects (two normal and four seizure patients) are included. The experiment result shows the proposed epileptic EEG classification algorithm achieves high accuracy. As well, the visualization and sonification algorithm exhibits a great help in nursing seizure patients and localizing the area of seizures. PMID:26737286

  1. [A child with ictal fear as the primary epileptic manifestation].

    PubMed

    Inutsuka, Miki; Ogino, Tatsuya; Yoshinaga, Harumi; Ohtsuka, Yoko; Oka, Eiji

    2003-07-01

    We report a 4-year-old boy with ictal fear as his primary epileptic manifestation. Following an arrest of motion, the boy started to scream and struggle with an expression of horror on his face. Oral automatisms appeared around the end of the seizure. Complex visual and gustatory hallucinations and pain in the left leg were also observed. Ictal and interictal scalp EEGs revealed epileptic discharges in bilateral frontal regions. Ictal SPECT (99 mTc-HMPAO) showed hyperperfusion in right medial temporal area. These findings suggest that ictal fear associated with other ictal manifestations such as various hallucinations and oral automatisms resulted from rapid spread of epileptic discharges from frontal lobes to the right anterior temporal region.

  2. 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…

  3. 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

  4. 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

  5. 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.

  6. Transient epileptic amnesia: clinical report of a cohort of patients.

    PubMed

    Lapenta, Leonardo; Brunetti, Valerio; Losurdo, Anna; Testani, Elisa; Giannantoni, Nadia Mariagrazia; Quaranta, Davide; Di Lazzaro, Vincenzo; Della Marca, Giacomo

    2014-07-01

    Transient epileptic amnesia is a seizure disorder, usually with onset in the middle-elderly and good response to low dosages of antiepileptic drugs. We describe the clinical, electroencephalography (EEG), and neuroimaging features of 11 patients with a temporal lobe epilepsy characterized by amnesic seizures as the sole or the main symptom. We outline the relevance of a detailed clinical history to recognize amnesic seizures and to avoid the more frequent misdiagnoses. Moreover, the response to monotherapy was usually good, although the epileptic disorder was symptomatic of acquired lesions in the majority of patients.

  7. [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

  8. 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.

  9. 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. PMID:26912639

  10. Proteomic profiling of the epileptic dentate gyrus

    PubMed Central

    Li, Aiqing; Choi, Yun-Sik; Dziema, Heather; Cao, Ruifeng; Cho, Hee-Yeon; Jung, Yeon Joo; Obrietan, Karl

    2010-01-01

    The development of epilepsy is often associated with marked changes in central nervous system cell structure and function. Along these lines, reactive gliosis and granule cell axonal sprouting within the dentate gyrus of the hippocampus are commonly observed in individuals with temporal lobe epilepsy. Here we used the pilocarpine model of temporal lobe epilepsy in mice to screen the proteome and phosphoproteome of the dentate gyrus to identify molecular events that are altered as part of the pathogenic process. Using a two-dimensional gel electrophoresis-based approach, followed by liquid chromatography-tandem mass spectrometry, 24 differentially expressed proteins, including 9 phosphoproteins, were identified. Functionally, these proteins were organized into several classes, including synaptic physiology, cell structure, cell stress, metabolism and energetics. The altered expression of three proteins involved in synaptic physiology, actin, profilin 1 and α-synuclein, was validated by secondary methods. Interestingly, marked changes in protein expression were detected in the supragranular cell region, an area where robust mossy fibers sprouting occurs. Together, these data provide new molecular insights into the altered protein profile of the epileptogenic dentate gyrus and point to potential pathophysiologic mechanisms underlying epileptogenesis. PMID:20608933

  11. The hippocampus, time, and memory across scales.

    PubMed

    Howard, Marc W; Eichenbaum, Howard

    2013-11-01

    A wealth of experimental studies with animals have offered insights about how neural networks within the hippocampus support the temporal organization of memories. These studies have revealed the existence of "time cells" that encode moments in time, much as the well-known "place cells" map locations in space. Another line of work inspired by human behavioral studies suggests that episodic memories are mediated by a state of temporal context that changes gradually over long time scales, up to at least a few thousand seconds. In this view, the "mental time travel" hypothesized to support the experience of episodic memory corresponds to a "jump back in time" in which a previous state of temporal context is recovered. We suggest that these 2 sets of findings could be different facets of a representation of temporal history that maintains a record at the last few thousand seconds of experience. The ability to represent long time scales comes at the cost of discarding precise information about when a stimulus was experienced--this uncertainty becomes greater for events further in the past. We review recent computational work that describes a mechanism that could construct such a scale-invariant representation. Taken as a whole, this suggests the hippocampus plays its role in multiple aspects of cognition by representing events embedded in a general spatiotemporal context. The representation of internal time can be useful across nonhippocampal memory systems.

  12. 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

  13. 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.

  14. Investigation of oxidative stress involvement in hippocampus in epilepsy model induced by pilocarpine.

    PubMed

    Freitas, R M

    2009-10-25

    The relationship between free radical and scavenger enzymes has been found in the epileptic phenomena and reactive oxygen species have been implicated in seizure-induced neurodegeneration. Using the epilepsy model obtained by systemic administration of pilocarpine in rats, we investigated the lipid peroxidation, nitrite content, superoxide dismutase (SOD) and catalase activities in the hippocampus of rats during chronic period. The enzyme activities as well as the lipid peroxidation and nitrite concentrations were measured using spectrophotometric methods and the results compared to values obtained from saline-treated animals. The superoxide dismutase and catalase activities increased during the chronic phase. In addition, lipid peroxidation and nitrite levels increased in same period in the hippocampus of animals observed during spontaneous recurrent seizures. Previous studies showed that animals presenting seizures and submitted to 24h of status epilepticus showed normal levels of superoxide dismutase and increased in catalase activities as well as an increase in hippocampal lipid peroxidation and nitrite concentrations. These results show a direct evidence of lipid peroxidation and nitrite during seizure activity that could be responsible for neuronal damage in the hippocampus of rats, during the establishment of pilocarpine model of epilepsy.

  15. Anti-Taenia solium larval stage Ig G antibodies in patients with epileptic seizures

    PubMed Central

    Parija, Subhash Chandra; Raman, Gireesh A

    2011-01-01

    Background: Cysticercosis is the most common differential diagnosis for epilepsy. The present study was carried out to assess the serological response among patients with epileptic seizures visiting JIPMER Hospital Puducherry. Materials and Methods: A total of 934 serum samples were collected from patients with epileptic seizures. A standardized questionnaire was designed to obtain information on the demographic, socioeconomic, environmental, and behavioral characteristics related to the transmission of infection. An enzyme-linked immunosorbent assay (ELISA) was used to detect the anti-Taenia solium larval stage IgG antibodies. Samples found reactive and inconclusive by ELISA were further tested by the enzyme immunotransfer blot (EITB). Results: The frequency of antibodies in the serum samples of the above-mentioned population was 16.2% by EITB. Anti-Taenia solium larval stage antibodies were detected in serum samples of 163 patients, out of which 27 (16.56%) patients belonged to the 0 – 15-year age group, 82 (50.30%) patients were in the 16 – 40-year age group, and 52 (31.90%) patients were above 41 years, respectively. Although the sera from males had higher OD values than those from females, the difference was not statistically significant. Out of 163 seropositive by ELISA, 152 (93.25%) were found to be positive by EITB. Out of the 152, 61 (40.13%) were farmers and 79 (51.97%) were office or factory workers. Conclusions: In conclusion, the results indicate a probable endemic situation and a high prevalence of cysticercosis in patients with epileptic seizures. Living in poor sanitary conditions seems to be an important factor related to human cysticercosis in Puducherry and the neighboring districts of Tamil Nadu. PMID:23508037

  16. 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,…

  17. Electroencephalographic examination of epileptic dogs under propofol restraint.

    PubMed

    Akos, Pákozdy; Thalhammer, Johann G; Leschnik, Michael; Halász, Péter

    2012-09-01

    The main aim of this study was to identify interictal epileptiform discharges in a group of dogs with seizures of known aetiology (symptomatic epilepsy, SE) and in dogs with idiopathic epilepsy (IE). Propofol was used for chemical restraint in all dogs. We found electroencephalographic (EEG) changes that could be considered epileptiform discharges (EDs) in 5 out of 40 dogs (12.5%). The EEG changes identified were spikes in four cases and periodic epileptiform discharges in one case. All EDs were seen in the SE group. We conclude that the interictal electroencephalographic examinations of propofolanaesthetised dogs suffering from IE and SE rarely show epileptic discharges and that the diagnostic value of such EEGs in the work-up for epilepsy seems to be low as epileptic discharges were unlikely to be detected. However, positive findings are more likely to be connected with SE. We found frequent, transient EEG phenomena (spindles, K-complexes, vertex waves, positive occipital sharp transients of sleep, cyclic alternating patterns), which are non-epileptic but their differentiation from epileptic phenomena is challenging.

  18. 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…

  19. EEG-confirmed epileptic activity in a cat with VGKC-complex/LGI1 antibody-associated limbic encephalitis.

    PubMed

    Pakozdy, Akos; Glantschnigg, Ursula; Leschnik, Michael; Hechinger, Harald; Moloney, Teresa; Lang, Bethan; Halasz, Peter; Vincent, Angela

    2014-03-01

    A 5-year-old, female client-owned cat presented with acute onset of focal epileptic seizures with orofacial twitching and behavioural changes. Magnetic resonance imaging showed bilateral temporal lobe hyperintensities and the EEG was consistent with ictal epileptic seizure activity. After antiepileptic and additional corticosteroid treatment, the cat recovered and by 10 months of follow-up was seizure-free without any problem. Retrospectively, antibodies to LGI1, a component of the voltage-gated potassium channel-complex, were identified. Feline focal seizures with orofacial involvement have been increasingly recognised in client-owned cats, and autoimmune limbic encephalitis was recently suggested as a possible aetiology. This is the first report of EEG, MRI and long-term follow-up of this condition in cats which is similar to human limbic encephalitis.

  20. 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.

  1. An 81.6 μW FastICA processor for epileptic seizure detection.

    PubMed

    Yang, Chia-Hsiang; Shih, Yi-Hsin; Chiueh, Herming

    2015-02-01

    To improve the performance of epileptic seizure detection, independent component analysis (ICA) is applied to multi-channel signals to separate artifacts and signals of interest. FastICA is an efficient algorithm to compute ICA. To reduce the energy dissipation, eigenvalue decomposition (EVD) is utilized in the preprocessing stage to reduce the convergence time of iterative calculation of ICA components. EVD is computed efficiently through an array structure of processing elements running in parallel. Area-efficient EVD architecture is realized by leveraging the approximate Jacobi algorithm, leading to a 77.2% area reduction. By choosing proper memory element and reduced wordlength, the power and area of storage memory are reduced by 95.6% and 51.7%, respectively. The chip area is minimized through fixed-point implementation and architectural transformations. Given a latency constraint of 0.1 s, an 86.5% area reduction is achieved compared to the direct-mapped architecture. Fabricated in 90 nm CMOS, the core area of the chip is 0.40 mm(2). The FastICA processor, part of an integrated epileptic control SoC, dissipates 81.6 μW at 0.32 V. The computation delay of a frame of 256 samples for 8 channels is 84.2 ms. Compared to prior work, 0.5% power dissipation, 26.7% silicon area, and 3.4 × computation speedup are achieved. The performance of the chip was verified by human dataset.

  2. The Dynamics of the Epileptic Brain Reveal Long-Memory Processes

    PubMed Central

    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

  3. An event map of memory space in the hippocampus

    PubMed Central

    Deuker, Lorena; Bellmund, Jacob LS; Navarro Schröder, Tobias; Doeller, Christian F

    2016-01-01

    The hippocampus has long been implicated in both episodic and spatial memory, however these mnemonic functions have been traditionally investigated in separate research strands. Theoretical accounts and rodent data suggest a common mechanism for spatial and episodic memory in the hippocampus by providing an abstract and flexible representation of the external world. Here, we monitor the de novo formation of such a representation of space and time in humans using fMRI. After learning spatio-temporal trajectories in a large-scale virtual city, subject-specific neural similarity in the hippocampus scaled with the remembered proximity of events in space and time. Crucially, the structure of the entire spatio-temporal network was reflected in neural patterns. Our results provide evidence for a common coding mechanism underlying spatial and temporal aspects of episodic memory in the hippocampus and shed new light on its role in interleaving multiple episodes in a neural event map of memory space. DOI: http://dx.doi.org/10.7554/eLife.16534.001 PMID:27710766

  4. Sparse generalized volterra model of human hippocampal spike train transformation for memory prostheses.

    PubMed

    Song, Dong; Robinson, Brian S; Hampson, Robert E; Marmarelis, Vasilis Z; Deadwyler, Sam A; Berger, Theodore W

    2015-01-01

    In order to build hippocampal prostheses for restoring memory functions, we build multi-input, multi-output (MIMO) nonlinear dynamical models of the human hippocampus. Spike trains are recorded from the hippocampal CA3 and CA1 regions of epileptic patients performing a memory-dependent delayed match-to-sample task. Using CA3 and CA1 spike trains as inputs and outputs respectively, second-order sparse generalized Laguerre-Volterra models are estimated with group lasso and local coordinate descent methods to capture the nonlinear dynamics underlying the spike train transformations. These models can accurately predict the CA1 spike trains based on the ongoing CA3 spike trains and thus will serve as the computational basis of the hippocampal memory prosthesis.

  5. Effects of single-dose neuropeptide Y on levels of hippocampal BDNF, MDA, GSH, and NO in a rat model of pentylenetetrazole-induced epileptic seizure.

    PubMed

    Kir, Hale Maral; Sahin, Deniz; Oztaş, Berrin; Musul, Mert; Kuskay, Sevinc

    2013-11-01

    Epilepsy is one of the most common neurological disorders, characterized by recurrent seizures, which may increase the content of reactive oxygen and nitrogen species. The objective of this study was to investigate the effects of Neuropeptide Y on oxidative and nitrosative balance and brain-derived neurotrophic factor levels induced by pentylenetetrazole (a standard convulsant drug) in the hippocampus of Wistar rats. Three groups of seven rats were treated intraperitoneally as follows: group 1 (saline + saline) 1 ml saline, group 2 (salin + Pentylenetetrazole) 1 ml saline 30 min before Pentylenetetrazole; and group 3 (Neuropeptide Y + Pentylenetetrazole) 60 μg/kg Neuropeptide Y 30 min before 60 mg/kg Pentylenetetrazole. After 24 h, the animals were euthanized by decapitation. Hippocampus were isolated to evaluate the malondialdehyde, glutathione, nitric oxide, and brain-derived neurotrophic factor levels in three rat groups. The results of this study demonstrated that while intraperitoneally administered neuropeptide Y did not result in a statistically significant difference in BDNF levels, its administration caused a statistically significant decrease in malondialdehyde and nitric oxide levels and an increase in glutathione levels in rats with pentylenetetrazole-induced epileptic seizure. Neuropeptide Y were able to reduce nitroxidative damage induced by pentylenetetrazole in the hippocampus of Wistar rats.

  6. [Video electroencephalographic diagnosis of epileptic and non-epileptic paroxysmal episodes in infants and children at the pre-school age].

    PubMed

    Pérez-Jiménez, Angeles; García-Fernández, Marta; Santiago, M del Mar; Fournier-Del Castillo, M Concepción

    2012-05-21

    The main usefulness of video electroencephalographic (video-EEG) monitoring lies in the fact that it allows proper classification of the type of epileptic seizure and epileptic syndrome, identification of minor seizures, location of the epileptogenic zone and differentiation between epileptic seizures and non-epileptic paroxysmal manifestations (NEPM). In infants and pre-school age children, the clinical signs with which epileptic seizures are expressed differ to those of older children, seizures with bilateral motor signs such as epileptic spasms, tonic and myoclonic seizures predominate, and seizures with interruption of activity or hypomotor seizures, and no prominent automatisms are observed. In children with focal epilepsies, focal and generalised signs are often superposed, both clinically and in the EEG. NEPM may be benign transitory disorders or they can be episodic symptoms of different neurological or psychopathological disorders. NEPM are often observed in children with mental retardation, neurological compromise or autism spectrum disorders, who present epileptic seizures and epileptiform abnormalities in the baseline EEG. It then becomes necessary to determine which episodes correspond to epileptic seizures and which do not. The NEPM that are most frequently registered in the video-EEG in infants and pre-school age children are unexpected sudden motor contractions ('spasms'), introspective tendencies, motor stereotypic movements and paroxysmal sleep disorders.

  7. Similarities and differences of acute nonconvulsive seizures and other epileptic activities following penetrating and ischemic brain injuries in rats.

    PubMed

    Lu, Xi-Chun May; Mountney, Andrea; Chen, Zhiyong; Wei, Guo; Cao, Ying; Leung, Lai Yee; Khatri, Vivek; Cunningham, Tracy; Tortella, Frank C

    2013-04-01

    The similarities and differences between acute nonconvulsive seizures (NCS) and other epileptic events, for example, periodic epileptiform discharges (PED) and intermittent rhythmic delta activities (IRDA), were characterized in rat models of penetrating and ischemic brain injuries. The NCS were spontaneously induced by either unilateral frontal penetrating ballistic-like brain injury (PBBI) or permanent middle cerebral artery occlusion (pMCAO), and were detected by continuous electroencephalogram (EEG) monitoring begun immediately after the injury and continued for 72 h or 24 h, respectively. Analysis of NCS profiles (incidence, frequency, duration, and time distribution) revealed a high NCS incidence in both injury models. The EEG waveform expressions of NCS and PED exhibited intrinsic variations that resembled human electrographic manifestations of post-traumatic and post-ischemic ictal and inter-ictal events, but these waveform variations were not distinguishable between the two types of brain injury. However, the NCS after pMCAO occurred more acutely and intensely (latency=0.6 h, frequency=25 episodes/rat) compared with the PBBI-induced NCS (latency=24 h, frequency=10 episodes/rat), such that the most salient features differentiating post-traumatic and post-ischemic NCS were the intensity and time distribution of the NCS profiles. After pMCAO, nearly 50% of the seizures occurred within the first 2 h of injury, whereas after PBBI, NCS occurred sporadically (0-5%/h) throughout the 72 h recording period. The PED were episodically associated with NCS. By contrast, the IRDA appeared to be independent of other epileptic events. This study provided comprehensive comparisons of post-traumatic and post-ischemic epileptic profiles. The identification of the similarities and differences across a broad spectrum of epileptic events may lead to differential strategies for post-traumatic and post-stroke seizure interventions.

  8. Abnormal expression and spatiotemporal change of Slit2 in neurons and astrocytes in temporal lobe epileptic foci: A study of epileptic patients and experimental animals.

    PubMed

    Fang, Min; Liu, Guang-Wei; Pan, Yu-Min; Shen, Lan; Li, Cheng-Shan; Xi, Zhi-Qin; Xiao, Fei; Wang, Liang; Chen, Dan; Wang, Xue-Feng

    2010-04-01

    Repellent guidance molecules provide targeting information to outgrowing axons along predetermined pathways during development. These molecules may also play a role in synaptic reorganization in the adult brain and thereby promote epileptogenesis. Our aim was to investigate the expression of Slit2, one of repellent guidance molecules, in temporal lobe epileptic foci from epileptic patients and experimental animals. Thirty-five temporal neocortex tissue samples from patients with intractable temporal lobe epilepsy (TLE) and fifteen histological normal temporal lobes from controls were selected. Fifty-four Sprague-Dawley rats were divided randomly into six groups, including five groups with epilepsy induced by lithium-pilocarpine administration and one control group. Temporal lobe tissue samples were taken from rats at 1, 7, 14, 30, and 60 days post-seizure and from controls. Expression of Slit2 was assessed by immunohistochemistry, immunofluorescence, and Western blot analysis. Slit2 was mainly expressed in neurons in human controls and in both neurons and astrocytes in TLE patients. Slit2 expression was significantly higher in TLE patients as compared with the controls. Slit2-positive cells were mainly neurons in the rat temporal lobe tissues of the control group, the acute period group, and the latent period group, while the Slit2-positive cells were mainly astrocytes in chronic phase. Compared with controls, Slit2 expression in animals in the TLE group gradually decreased from days 1 to 14 post-seizure, but then increased over the levels seen in controls, to peak levels at days 30 and 60. These results suggest that Slit2 may play an important role in the pathogenesis of TLE.

  9. 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.

  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.

  11. 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

  12. Resistance exercise improves hippocampus-dependent memory.

    PubMed

    Cassilhas, R C; Lee, K S; Venâncio, D P; Oliveira, M G M; Tufik, S; de Mello, M T

    2012-12-01

    It has been demonstrated that resistance exercise improves cognitive functions in humans. Thus, an animal model that mimics this phenomenon can be an important tool for studying the underlying neurophysiological mechanisms. Here, we tested if an animal model for resistance exercise was able to improve the performance in a hippocampus-dependent memory task. In addition, we also evaluated the level of insulin-like growth factor 1/insulin growth factor receptor (IGF-1/IGF-1R), which plays pleiotropic roles in the nervous system. Adult male Wistar rats were divided into three groups (N = 10 for each group): control, SHAM, and resistance exercise (RES). The RES group was submitted to 8 weeks of progressive resistance exercise in a vertical ladder apparatus, while the SHAM group was left in the same apparatus without exercising. Analysis of a cross-sectional area of the flexor digitorum longus muscle indicated that this training period was sufficient to cause muscle fiber hypertrophy. In a step-through passive avoidance task (PA), the RES group presented a longer latency than the other groups on the test day. We also observed an increase of 43 and 94% for systemic and hippocampal IGF-1 concentration, respectively, in the RES group compared to the others. A positive correlation was established between PA performance and systemic IGF-1 (r = 0.46, P < 0.05). Taken together, our data indicate that resistance exercise improves the hippocampus-dependent memory task with a concomitant increase of IGF-1 level in the rat model. This model can be further explored to better understand the effects of resistance exercise on brain functions. PMID:22930413

  13. 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

  14. 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

  15. Epileptic seizure prediction by non-linear methods

    DOEpatents

    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.

  16. 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.

  17. 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.

  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.

  19. [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

  20. 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

  1. The Role of Astroglia in the Epileptic Brain

    PubMed Central

    Losi, Gabriele; Cammarota, Mario; Carmignoto, Giorgio

    2012-01-01

    Epilepsies comprise a family of multifactorial neurological disorders that affect at least 50 million people worldwide. Despite a long history of neurobiological and clinical studies the mechanisms that lead the brain network to a hyperexcitable state and to the intense, massive neuronal discharges reflecting a seizure episode are only partially defined. Most epilepsies of genetic origin are related to mutations in ionic channels that cause neuronal hyperexcitability. However, idiopathic epilepsies of unclear origin represent the majority of these brain disorders. A large body of evidence suggests that in the epileptic brain neurons are not the only players. Indeed, the glial cell astrocyte is known to be morphologically and functionally altered in different types of epilepsy. Although it is unclear whether these astrocyte dysfunctions can have a causative role in epileptogenesis, the hypothesis that astrocytes contribute to epileptiform activities recently received a considerable experimental support. Notably, currently used antiepileptic drugs, that act mainly on neuronal ion channels, are ineffective in a large group of patients. Clarifying astrocyte functions in the epileptic brain tissue could unveil astrocytes as novel therapeutic targets. In this review we present first a short overview on the role of astrocytes in the epileptic brain starting from the “historical” observations on their fundamental modulation of brain homeostasis, such as the control of water content, ionic equilibrium, and neurotransmitters concentrations. We then focus our review on most recent studies that hint at a distinct contribution of these cells in the generation of focal epileptiform activities. PMID:22807916

  2. 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

  3. [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.

  4. [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

  5. [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.

  6. [Studies of the mechanisms of spreading of epileptic discharges in the central nervous system].

    PubMed

    Trabka, W

    1989-01-01

    The process of spreading of epileptic discharges in central nervous system has to be discussed in two points of view; as a propagation of signals in neuronal networks and as a process of dynamics changes in neuronal circuits and nets. On the base of the spreading of afterdischarges between entorhinal cortex and both hippocampi we discussed time and space relations in spreading of epileptic discharges, and automatic analytical methods in localization of epileptic focus. Spreading epileptic discharge is not only the symptom of pathologic function of system but it simultaneously changes the dynamics of system in which it spreads and causes epileptic destabilization of neuronal circuits and nets. The above mechanisms after theoretical investigations play also important role in evaluation of secondary epileptic foci and posttraumatic epilepsy.

  7. The hippocampus and memory for orderly stimulus relations

    PubMed Central

    Dusek, Jeffery A.; Eichenbaum, Howard

    1997-01-01

    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

  8. 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

  9. Impaired neurovascular coupling to ictal epileptic activity and spreading depolarization in a patient with subarachnoid hemorrhage: Possible link to blood–brain barrier dysfunction

    PubMed Central

    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.

    2013-01-01

    SUMMARY 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

  10. Altered expression and function of small-conductance (SK) Ca2+-activated K+ channels in pilocarpine-treated epileptic rats

    PubMed Central

    Oliveira, Mauro S.; Skinner, Frank; Arshadmansab, Massoud F.; Garcia, Ileana; Mello, Carlos F.; Knaus, Hans-Günther; Ermolinsky, Boris S.; Pacheco Otalora, Luis F.; Garrido-Sanabria, Emilio R.

    2010-01-01

    Small conductance calcium (Ca2+) activated SK channels are critical regulators of neuronal excitability in hippocampus. Accordingly, these channels are thought to play a key role in controlling neuronal activity in acute models of epilepsy. In this study, we investigate the expression and function of SK channels in the pilocarpine model of mesial temporal lobe epilepsy. For this purpose, protein expression was assessed using western blotting assays and gene expression was analyzed using TaqMan-based probes and the quantitative real-time polymerase chain reaction (qPCR) comparative method delta-delta cycle threshold (ΔΔCT) in samples extracted from control and epileptic rats. In addition, the effect of SK channel antagonist UCL1684 and agonist NS309 on CA1 evoked population spikes was studied in hippocampal slices. Western blotting analysis showed a significant reduction in the expression of SK1 and SK2 channels at 10 days following status epilepticus (SE), but levels recovered at 1 month and at more than 2 months after SE. In contrast, a significant down-regulation of SK3 channels was detected after 10 days of SE. Analysis of gene expression by qPCR revealed a significant reduction of transcripts for SK2 (Kcnn1) and SK3 (Kcnn3) channels as early as 10 days following pilocarpine-induced SE and during the chronic phase of the pilocarpine model. Moreover, bath application of UCL1684 (100 nM for 15 min) induced a significant increase of the population spike amplitude and number of spikes in the hippocampal CA1 area of slices obtained control and chronic epileptic rats. This effect was obliterated by co-administration of UCL1684 with SK channel agonist NS309 (1 μM). Application of NS309 failed to modify population spikes in the CA1 area of slices taken from control and epileptic rats. These data indicate an abnormal expression of SK channels and a possible dysfunction of these channels in experimental MTLE. PMID:20553876

  11. Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy associated with VGKC-complex antibodies.

    PubMed

    Suleiman, Jehan; Brenner, Tanja; Gill, Deepak; Troedson, Christopher; Sinclair, Adriane J; Brilot, Fabienne; Vincent, Angela; Lang, Bethan; Dale, Russell C

    2011-11-01

    Autoantibodies that bind to voltage-gated potassium-channel complex proteins (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis presenting with cognitive impairment and seizures. Recently, VGKC-complex antibodies have been described in a few children with limbic encephalitis, and children with unexplained encephalitis presenting with status epilepticus. We report a case of infantile-onset epileptic spasms and developmental delay compatible with epileptic encephalopathy. Our patient was a female infant, aged 4 months at presentation. She had evidence of immune activation in the central nervous system with elevated cerebrospinal fluid neopterin and mirrored oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex antibodies were elevated (201 pmol/L, normal<100), but extended antibody testing, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2), was negative. The patient showed a partial response to steroid treatment, which was started late in the disease course. On review at 13 months of age, her development was consistent with an age of 5 to 6 months. These results suggest that VGKC-complex antibodies might represent a marker of immune therapy responsiveness in a subgroup of patients with infantile epileptic encephalopathy.

  12. 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

  13. Increased excitability and metabolism in pilocarpine induced epileptic rats: effect of Bacopa monnieri.

    PubMed

    Mathew, Jobin; Paul, Jes; Nandhu, M S; Paulose, C S

    2010-09-01

    We have evaluated the acetylcholine esterase and malate dehydrogenase activity in the muscle, epinephrine, norepinephrine, insulin and T3 content in the serum of epileptic rats. Acetylcholine esterase and malate dehydrogenase activity increased in the muscle and decreased in the heart of the epileptic rats compared to control. Insulin and T3 content were increased significantly in the serum of the epileptic rats. Our results suggest that repetitive seizures resulted in increased metabolism and excitability in epileptic rats. Bacopa monnieri and Bacoside-A treatment prevents the occurrence of seizures there by reducing the impairment on peripheral nervous system.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Transfer Function between EEG and BOLD Signals of Epileptic Activity

    PubMed Central

    Leite, Marco; Leal, Alberto; Figueiredo, Patrícia

    2013-01-01

    Simultaneous electroencephalogram (EEG)-functional Magnetic Resonance Imaging (fMRI) recordings have seen growing application in the evaluation of epilepsy, namely in the characterization of brain networks related to epileptic activity. In EEG-correlated fMRI studies, epileptic events are usually described as boxcar signals based on the timing information retrieved from the EEG, and subsequently convolved with a hemodynamic response function to model the associated Blood Oxygen Level Dependent (BOLD) changes. Although more flexible approaches may allow a higher degree of complexity for the hemodynamics, the issue of how to model these dynamics based on the EEG remains an open question. In this work, a new methodology for the integration of simultaneous EEG-fMRI data in epilepsy is proposed, which incorporates a transfer function from the EEG to the BOLD signal. Independent component analysis of the EEG is performed, and a number of metrics expressing different models of the EEG-BOLD transfer function are extracted from the resulting time courses. These metrics are then used to predict the fMRI data and to identify brain areas associated with the EEG epileptic activity. The methodology was tested on both ictal and interictal EEG-fMRI recordings from one patient with a hypothalamic hamartoma. When compared to the conventional analysis approach, plausible, consistent, and more significant activations were obtained. Importantly, frequency-weighted EEG metrics yielded superior results than those weighted solely on the EEG power, which comes in agreement with previous literature. Reproducibility, specificity, and sensitivity should be addressed in an extended group of patients in order to further validate the proposed methodology and generalize the presented proof of concept. PMID:23355832

  4. 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

  5. Attention in schizophrenia and in epileptic psychosis.

    PubMed

    Kairalla, I C J; Mattos, P E L; Hoexter, M Q; Bressan, R A; Mari, J J; Shirakawa, I

    2008-01-01

    The adaptive behavior of human beings is usually supported by rapid monitoring of outstanding events in the environment. Some investigators have suggested that a primary attention deficit might trigger symptoms of schizophrenia. In addition, researchers have long discussed the relationship between schizophrenia and the schizophrenia-like psychosis of epilepsy (SLPE). On the basis of these considerations, the objective of the present study was to investigate attention performance of patients with both disorders. Patient age was 18 to 60 years, and all patients had received formal schooling for at least four years. Patients were excluded if they had any systemic disease with neurologic or psychiatric comorbidity, or a history of brain surgery. The computer-assisted TAVIS-2R test was applied to all patients and to a control group to evaluate and discriminate between selective, alternating and sustained attention. The TAVIS-2R test is divided into three parts: one for selective attention (5 min), the second for alternating attention (5 min), and the third for the evaluation of vigilance or sustained attention (10 min). The same computer software was used for statistical analysis of reaction time, omission errors, and commission errors. The sample consisted of 36 patients with schizophrenia, 28 with interictal SLPE, and 47 healthy controls. The results of the selective attention tests for both patient groups were significantly lower than that for controls. The patients with schizophrenia and SLPE performed differently in the alternating and sustained attention tests: patients with SLPE had alternating attention deficits, whereas patients with schizophrenia showed deficits in sustained attention. These quantitative results confirmed the qualitative clinical observations for both patient groups, that is, that patients with schizophrenia had difficulties in focusing attention, whereas those with epilepsy showed perseveration in attention focus.

  6. Neuroendocrinal study of depression in male epileptic patients.

    PubMed

    Afifi, Samah; Fadel, Wael; Morad, Heba; Eldod, Abdo; Gad, Elsayed; Arfken, Cynthia L; Samra, Abou; Boutros, Nash

    2011-01-01

    Endocrine changes are reported in both epilepsy and depression. The interrelationships between mood, epilepsy, and endocrine changes are not well characterized. The authors included 40 epileptic patients (20 depressed, 20 nondepressed) and 20 healthy subjects. All patients had an electroencephalogram, and were given the Hamilton Rating Scale for Depression. All subjects were tested for serum levels of cortisol, prolactin, testosterone, and thyroid hormones. Patients were medication-free. Patients had elevated prolactin and cortisol and reduced serum testosterone relative to control subjects. Depressed patients had higher cortisol levels than nondepressed. Data suggest that the effects of epilepsy and depression on cortisol, but not other hormones, may be additive.

  7. [Specificities of the epileptic women (oral contraceptives, pregnancy)].

    PubMed

    Dupont, Sophie

    2011-03-01

    The enzyme-inducing antiepileptic drugs such as carbamazepine, phenytoin, barbiturates, oxcarbazepine do not allow oral contraceptives. The pregnancy must be planned. Every patient in childbearing age should be informed by her practitioner. The rule is to optimize the antiepileptic treatment before the pregnancy: less drugs, less dosages. This optimization will depend on the epileptic syndrome and the nature of the treatment. Valproate of sodium should be avoided, if possible, during pregnancy. Preconceptional supplementation by folic acid should be considered. Antiepileptic drugs monitoring is required during pregnancy. Natural delivery with peridural anaesthesiology is mandatory. The breast feeding must be considered individually. PMID:21216127

  8. Psycho-Social Aspects of Educating Epileptic Children: Roles for School Psychologists.

    ERIC Educational Resources Information Center

    Frank, Brenda B.

    1985-01-01

    Epileptic children may have physical and emotional needs which can interfere with learning and socialization. Current prevalence estimates, definitions, and classifications of epilepsy are surveyed. Factors affecting the epileptic child's school performance and specific learning problems are addressed. Specific roles are presented for school…

  9. 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

  10. Brain-derived neurotrophic factor superinduction parallels anti-epileptic--neuroprotective treatment in the pilocarpine epilepsy model.

    PubMed

    Biagini, G; Avoli, M; Marcinkiewicz, J; Marcinkiewicz, M

    2001-03-01

    Antiepileptic drugs provide neuroprotection in several animal models of brain damage, including those induced by status epilepticus (SE). The mechanisms involved in this action are unknown, but neurotrophic factors such as brain-derived neurotrophic factor (BDNF) may play a role. In this study we investigated the changes in BDNF levels in rats in which SE had been induced by pilocarpine injection (400 mg/kg i.p.) and continued for several hours (unprotected group). In other animals (protected groups), SE was suppressed after 30 min by intraperitoneal injection of either diazepam (10 mg/kg) + pentobarbital (30 mg/kg) or paraldehyde (0.3 mg/kg). In diazepam + pentobarbital-treated rats the hippocampal damage caused by SE was significantly lower (p < 0.05) than in unprotected animals. In addition, 2 and 24 h after pilocarpine injection, the levels of BDNF mRNA were moderately increased in the unprotected group, but 'superinduced' in protected animals, especially in the neocortex and hippocampus. A time-dependent increase in BDNF immunoreactivity was also found by western blot analysis in rats treated with diazepam + pentobarbital. In contrast, a decrease of BDNF immunoreactivity occurred in the unprotected group. In conclusion, these results show that neuroprotection induced by anti-epileptic drugs in pilocarpine-treated rats is accompanied by strong potentiation of BDNF synthesis in brain regions involved in SE.

  11. The hippocampus supports multiple cognitive processes through relational binding and comparison

    PubMed Central

    Olsen, Rosanna K.; Moses, Sandra N.; Riggs, Lily; Ryan, Jennifer D.

    2012-01-01

    It has been well established that the hippocampus plays a pivotal role in explicit long-term recognition memory. However, findings from amnesia, lesion and recording studies with non-human animals, eye-movement recording studies, and functional neuroimaging have recently converged upon a similar message: the functional reach of the hippocampus extends far beyond explicit recognition memory. Damage to the hippocampus affects performance on a number of cognitive tasks including recognition memory after short and long delays and visual discrimination. Additionally, with the advent of neuroimaging techniques that have fine spatial and temporal resolution, findings have emerged that show the elicitation of hippocampal responses within the first few 100 ms of stimulus/task onset. These responses occur for novel and previously viewed information during a time when perceptual processing is traditionally thought to occur, and long before overt recognition responses are made. We propose that the hippocampus is obligatorily involved in the binding of disparate elements across both space and time, and in the comparison of such relational memory representations. Furthermore, the hippocampus supports relational binding and comparison with or without conscious awareness for the relational representations that are formed, retrieved and/or compared. It is by virtue of these basic binding and comparison functions that the reach of the hippocampus extends beyond long-term recognition memory and underlies task performance in multiple cognitive domains. PMID:22661938

  12. New clinical findings on the longevity gene in disease, health, & longevity: Sirtuin 1 often decreases with advanced age & serious diseases in most parts of the human body, while relatively high & constant Sirtuin 1 regardless of age was first found in the hippocampus of supercentenarians.

    PubMed

    Omura, Yoshiaki; Lu, Dominic P; Jones, Marilyn; O'Young, Brian; Duvvi, Harsha; Paluch, Kamila; Shimotsuura, Yasuhiro; Ohki, Motomu

    2011-01-01

    The expression of the longevity gene, Sirtuin 1, was non-invasively measured using Electro-Magnetic Field (EMF) resonance phenomenon between a known amount of polyclonal antibody of the C-terminal of Sirtuin 1 & Sirtuin 1 molecule inside of the body. Our measurement of over 100 human adult males and females, ranging between 20-122 years old, indicated that the majority of subjects had Sirtuin 1 levels of 5-10 pg BDORT units in most parts of the body. When Sirtuin 1 was less than 1 pg, the majority of the people had various degrees of tumors or other serious diseases. When Sirtuin 1 levels were less than 0.25 pg BDORT units, a high incidence of AIDS was also detected. Very few people had Sirtuin 1 levels of over 25 pg BDORT units in most parts of the body. We selected 7 internationally recognized supercentenarians who lived between 110-122 years old. To our surprise, most of their body Sirtuin 1 levels were between 2.5-10 pg BDORT units. However, by evaluating different parts of the brain, we found that both sides of the Hippocampus had a much higher amount of Sirtuin 1, between 25-100 pg BDORT units. With most subjects, Sirtuin 1 was found to be higher in the Hippocampus than in the rest of the body and remains relatively constant regardless of age. We found that Aspartame, plastic eye contact lenses, and asbestos in dental apparatuses, which reduce normal cell telomeres, also significantly reduce Sirtuin 1. In addition, we found that increasing normal cell telomere by electrical or mechanical stimulation of True ST-36 increases the expression of the Sirtuin 1 gene in people in which expression is low. This measurement of Sirtuin 1 in the Hippocampus has become a reliable indicator for detecting potential longevity of an individual.

  13. Characterization of ictal slow waves in epileptic spasms.

    PubMed

    Honda, Ryoko; Saito, Yoshiaki; Okumura, Akihisa; Abe, Shinpei; Saito, Takashi; Nakagawa, Eiji; Sugai, Kenji; Sasaki, Masayuki

    2015-12-01

    We characterized the clinico-neurophysiological features of epileptic spasms, particularly focusing on high-voltage slow waves during ictal EEG. We studied 22 patients with epileptic spasms recorded during digital video-scalp EEG, including five individuals who still had persistent spasms after callosotomy. We analysed the duration, amplitude, latency to onset of electromyographic bursts, and distribution of the highest positive and negative peaks of slow waves in 352 spasms. High-voltage positive slow waves preceded the identifiable muscle contractions of spasms. The mean duration of these positive waves was 569±228 m, and the mean latency to electromyographic onset was 182±127 m. These parameters varied markedly even within a patient. The highest peak of the positive component was distributed in variable regions, which was not consistent with the location of lesions on MRI. The peak of the negative component following the positivity was distributed in the neighbouring or opposite areas of the positive peak distribution. No changes were evident in the pre- or post-surgical distributions of the positive peak, or in the interhemispheric delay between both hemispheres, in individuals with callosotomy. Our data imply that ictal positive slow waves are the most common EEG changes during spasms associated with a massive motor component. Plausible explanations for these widespread positive slow waves include the notion that EEG changes possibly reflect involvement of both cortical and subcortical structures.

  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.

  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.

  16. Noninvasive real time tomographic imaging of epileptic foci and networks.

    PubMed

    Xiang, Liangzhong; Ji, Lijun; Zhang, Tao; Wang, Bo; Yang, Jianjun; Zhang, Qizhi; Jiang, Max S; Zhou, Junli; Carney, Paul R; Jiang, Huabei

    2013-02-01

    While brain imaging and electrophysiology play a central role in neuroscience research and in the evaluation of neurological disorders, a single noninvasive modality that offers both high spatial and temporal resolution is currently not available. Here we show in an acute epilepsy rat model that photoacoustic tomography (PAT) can noninvasively track seizure brain dynamics with both high spatial and temporal resolution, and at a depth that is clinically relevant. The noninvasive yet whole surface and depth capabilities of the PAT system allowed us to actually see what is happening during ictogenesis in terms of seizure onset and spread. Both seizure onset and propagation were tomographically detected at a spatial resolution of 150μm and a temporal resolution of 300ms, respectively. The current study lends support to the theory that seizure onset and spread involves a rich interplay between multiple cortical and subcortical brain areas during the onset and spread of epileptic seizures. Dynamical changes of vasculature during epileptiform events were also detected with high spatiotemporal resolution. Together, these findings suggest that PAT represents a powerful tool for noninvasively mapping seizure onset and propagation patterns, and the 'functional' connectivity within epileptic brain networks. PMID:23128072

  17. 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

  18. Neuroimaging and spectroscopy in children with epileptic encephalopathies

    PubMed Central

    Parker, A.; Ferrie, C.; Keevil, S.; Newbold, M.; Cox, T.; Maisey, M.; Robinson, R.

    1998-01-01

    AIMS—To investigate the nature of the unifocal cortical abnormalities on FDG positron emission tomography (PET) in children with an epileptic encephalopathy but no focal abnormality on electroencephalogram or standard magnetic resonance imaging (MRI).
METHODS—Repeat FDG PET, surface rendered high resolution MRI, and single voxel magnetic resonance proton spectroscopy of the areas of abnormal metabolism compared to the contralateral side in 11children aged 2 to 12 years. Imaging was repeated after a median of 13months.
RESULTS—Visual analysis of repeat FDG PET revealed similar abnormalities in 10 of 11 children. Semiquantitative analysis revealed similar sited abnormalities in eight children. One child with ictal hypermetabolism initially had an inconsistent second scan. Magnetic resonance spectra in three children showed the N-acetylaspartate/choline ratio was lower in the hypometabolic focus than in the reciprocal area on the opposite side, in two children it was higher, and in one child it was equal. Surface rendered MRI was normal in seven of eight children, and showed temporal lobe asymmetry in one.
CONCLUSION—In children with established epileptic encephalopathies most hypometabolic areas on FDG PET are stable over time. While focal neuronal loss is likely in these areas in some children, microdysplasias or other focal cortical dysplasias are probable in others.

 PMID:9771250

  19. Epileptic neuronal networks: methods of identification and clinical relevance.

    PubMed

    Stefan, Hermann; Lopes da Silva, Fernando H

    2013-01-01

    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.

  20. Encoding and reactivation patterns predictive of successful memory performance are topographically organized along the longitudinal axis of the hippocampus.

    PubMed

    Nakamura, Nozomu H; Sauvage, Magdalena M

    2016-01-01

    An ongoing debate in human memory research is whether the encoding and the retrieval of memory engage the same part of the hippocampus and the same cells, or whether encoding preferentially involves the anterior part of the hippocampus and retrieval its posterior part. Here, we used a human to rat translational behavioral approach combined to high-resolution molecular imaging to address this issue. We showed that successful memory performance is predicted by encoding and reactivation patterns only in the dorsal part of the rat hippocampus (posterior part in humans), but not in the ventral part (anterior part in humans). Our findings support the view that the encoding and the retrieval processes per se are not segregated along the longitudinal axis of the hippocampus, but that activity predictive of successful memory is and concerns specifically the dorsal part of the hippocampus. In addition, we found evidence that these processes are likely to be mediated by the activation/reactivation of the same cells at this level. Given the translational character of the task, our results suggest that both the encoding and the retrieval processes take place in the same cells of the posterior part of the human hippocampus. PMID:26174148

  1. 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.

  2. Histaminergic neurons protect the developing hippocampus from kainic acid-induced neuronal damage in an organotypic coculture system.

    PubMed

    Kukko-Lukjanov, Tiina-Kaisa; Soini, Sanna; Taira, Tomi; Michelsen, Kimmo A; Panula, Pertti; Holopainen, Irma E

    2006-01-25

    The central histaminergic neuron system inhibits epileptic seizures, which is suggested to occur mainly through histamine 1 (H1) and histamine 3 (H3) receptors. However, the importance of histaminergic neurons in seizure-induced cell damage is poorly known. In this study, we used an organotypic coculture system and confocal microscopy to examine whether histaminergic neurons, which were verified by immunohistochemistry, have any protective effect on kainic acid (KA)-induced neuronal damage in the developing hippocampus. Fluoro-Jade B, a specific marker for degenerating neurons, indicated that, after the 12 h KA (5 microM) treatment, neuronal damage was significantly attenuated in the hippocampus cultured together with the posterior hypothalamic slice containing histaminergic neurons [HI plus HY (POST)] when compared with the hippocampus cultured alone (HI) or with the anterior hypothalamus devoid of histaminergic neurons. Moreover, alpha-fluoromethylhistidine, an inhibitor of histamine synthesis, eliminated the neuroprotective effect in KA-treated HI plus HY (POST), and extracellularly applied histamine (1 nM to 100 microM) significantly attenuated neuronal damage only at 1 nM concentration in HI. After the 6 h KA treatment, spontaneous electrical activity registered in the CA1 subregion contained significantly less burst activity in HI plus HY (POST) than in HI. Finally, in KA-treated slices, the H3 receptor antagonist thioperamide enhanced the neuroprotective effect of histaminergic neurons, whereas the H1 receptor antagonists triprolidine and mepyramine dose-dependently decreased the neuroprotection in HI plus HY (POST). Our results suggest that histaminergic neurons protect the developing hippocampus from KA-induced neuronal damage, with regulation of neuronal survival being at least partly mediated through H1 and H3 receptors.

  3. 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

  4. Meditation improves clinicoelectroencephalographic measures in drug-resistant epileptics.

    PubMed

    Deepak, K K; Manchanda, S K; Maheshwari, M C

    1994-03-01

    Eleven adults suffering from drug-resistant epilepsies were given meditation practice, while another nine adults acted as waiting list controls. All patients were on antiepileptic drugs and their serum drug levels were monitored regularly. Patients in the intervention group were given training in meditation, and they practiced meditation 20 minutes a day for one year. They showed a significant reduction in seizure frequency and duration, an increase in the dominant background EEG frequency, a reduction in mean spectral intensity of the 0.7-7.7 Hz segment, and an increment in mean spectral intensity in the 8-12 Hz segment of the EEG. All changes were statistically significant. Control patients did not show significant changes in seizure frequency and duration during the observation period of one year. The results indicate that continued meditation practice is of substantial help in improving the clinicoelectrographic picture in drug-resistant epileptics.

  5. Epileptic Encephalopathy in Children with Risk Factors for Brain Damage

    PubMed Central

    Ricardo-Garcell, Josefina; Harmony, Thalía; Porras-Kattz, Eneida; Colmenero-Batallán, Miguel J.; Barrera-Reséndiz, Jesús E.; Fernández-Bouzas, Antonio; Cruz-Rivero, Erika

    2012-01-01

    In the study of 887 new born infants with prenatal and perinatal risk factors for brain damage, 11 children with West syndrome that progressed into Lennox-Gastaut syndrome and another 4 children with Lennox-Gastaut syndrome that had not been preceded by West syndrome were found. In this study we present the main findings of these 15 subjects. In all infants multifactor antecedents were detected. The most frequent risk factors were prematurity and severe asphyxia; however placenta disorders, sepsis, and hyperbilirubinemia were also frequent. In all infants MRI direct or secondary features of periventricular leukomalacia were observed. Followup of all infants showed moderate to severe neurodevelopmental delay as well as cerebral palsy. It is concluded that prenatal and perinatal risk factors for brain damage are very important antecedents that should be taken into account to follow up those infants from an early age in order to detect and treat as early as possible an epileptic encephalopathy. PMID:22957240

  6. Compulsive versifying after treatment of transient epileptic amnesia.

    PubMed

    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.

  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. The approach to patients with "non-epileptic seizures"

    PubMed Central

    Mellers, J

    2005-01-01

    Up to one fifth of patients who present to specialist clinics with seizures do not have epilepsy. The majority of such patients suffer from psychologically mediated episodes; dissociative seizures, often referred to as "non-epileptic seizures". This paper describes the diagnostic evaluation of seizure disorders, including clinical assessment and the role of special investigations. The organic and psychiatric imitators of epilepsy are outlined and findings on psychiatric assessment are reviewed. This group of patients often proves difficult to engage in appropriate treatment and an approach to explaining the diagnosis is described. As yet there are no controlled trials of treatment in this disorder but preliminary evidence suggests cognitive behavioural therapy is both a rational and promising way forward. PMID:16085740

  9. 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

  10. Navigating from hippocampus to parietal cortex

    PubMed Central

    Whitlock, Jonathan R.; Sutherland, Robert J.; Witter, Menno P.; Moser, May-Britt; Moser, Edvard I.

    2008-01-01

    The navigational system of the mammalian cortex comprises a number of interacting brain regions. Grid cells in the medial entorhinal cortex and place cells in the hippocampus are thought to participate in the formation of a dynamic representation of the animal's current location, and these cells are presumably critical for storing the representation in memory. To traverse the environment, animals must be able to translate coordinate information from spatial maps in the entorhinal cortex and hippocampus into body-centered representations that can be used to direct locomotion. How this is done remains an enigma. We propose that the posterior parietal cortex is critical for this transformation. PMID:18812502

  11. Failure of adaptive self-organized criticality during epileptic seizure attacks.

    PubMed

    Meisel, Christian; Storch, Alexander; Hallmeyer-Elgner, Susanne; Bullmore, Ed; Gross, Thilo

    2012-01-01

    Critical dynamics are assumed to be an attractive mode for normal brain functioning as information processing and computational capabilities are found to be optimal in the critical state. Recent experimental observations of neuronal activity patterns following power-law distributions, a hallmark of systems at a critical state, have led to the hypothesis that human brain dynamics could be poised at a phase transition between ordered and disordered activity. A so far unresolved question concerns the medical significance of critical brain activity and how it relates to pathological conditions. Using data from invasive electroencephalogram recordings from humans we show that during epileptic seizure attacks neuronal activity patterns deviate from the normally observed power-law distribution characterizing critical dynamics. The comparison of these observations to results from a computational model exhibiting self-organized criticality (SOC) based on adaptive networks allows further insights into the underlying dynamics. Together these results suggest that brain dynamics deviates from criticality during seizures caused by the failure of adaptive SOC.

  12. 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

  13. 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

    2016-08-17

    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.

  14. Stress effects on the hippocampus: a critical review.

    PubMed

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

    2015-09-01

    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.

  15. 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

  16. 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.

  17. Independent Neuronal Representation of Facial and Vocal Identity in the Monkey Hippocampus and Inferotemporal Cortex.

    PubMed

    Sliwa, Julia; Planté, Aurélie; Duhamel, Jean-René; Wirth, Sylvia

    2016-03-01

    Social interactions make up to a large extent the prime material of episodic memories. We therefore asked how social signals are coded by neurons in the hippocampus. Human hippocampus is home to neurons representing familiar individuals in an abstract and invariant manner ( Quian Quiroga et al. 2009). In contradistinction, activity of rat hippocampal cells is only weakly altered by the presence of other rats ( von Heimendahl et al. 2012; Zynyuk et al. 2012). We probed the activity of monkey hippocampal neurons to faces and voices of familiar and unfamiliar individuals (monkeys and humans). Thirty-one percent of neurons recorded without prescreening responded to faces or to voices. Yet responses to faces were more informative about individuals than responses to voices and neuronal responses to facial and vocal identities were not correlated, indicating that in our sample identity information was not conveyed in an invariant manner like in human neurons. Overall, responses displayed by monkey hippocampal neurons were similar to the ones of neurons recorded simultaneously in inferotemporal cortex, whose role in face perception is established. These results demonstrate that the monkey hippocampus participates in the read-out of social information contrary to the rat hippocampus, but possibly lack an explicit conceptual coding of as found in humans.

  18. Alteration of Scn3a expression is mediated via CpG methylation and MBD2 in mouse hippocampus during postnatal development and seizure condition.

    PubMed

    Li, Hai-Jun; Wan, Rui-Ping; Tang, Ling-Jia; Liu, Shu-Jing; Zhao, Qi-Hua; Gao, Mei-Mei; Yi, Yong-Hong; Liao, Wei-Ping; Sun, Xiao-Fang; Long, Yue-Sheng

    2015-01-01

    Increased expression of sodium channel SCN3A, an embryonic-expressed gene, has been identified in epileptic tissues, which is believed to contribute to the development of epilepsy. However, the regulatory mechanism of SCN3A expression under epileptic condition is still unknown. Here we showed a high level of Scn3a mRNA expression in mouse embryonic hippocampus with gradually decreasing to a low level during the postnatal development and a methylation of a specific CpG site (-39C) in the Scn3a promoter was increased in hippocampus during postnatal development, corresponding to the downregulation of Scn3a expression. Furthermore, in vitro methylation and -39C>T mutation of the Scn3a promoter decreased the reporter gene expression, suggesting an important role of the -39C site in regulating gene expression. We then demonstrated that the sequence containing -39C was a MBD2-binding motif and the CpG methylation of the promoter region increased the capability of MBD2's binding to the motif. Knockdown of MBD2 in mouse N1E-115 cells led to the -39C methylation and the downregulation of Scn3a transcription by decreasing the Scn3a promoter activity. In the hippocampus of seizure mice, the expressions of Scn3a and Mbd2 were upregulated after 10-day KA treatment. At the same time point, the -39C site was demethylated and the capability of MBD2's binding to the Scn3a promoter motif was decreased. Taken together, these findings suggest that CpG methylation and MBD2 are involved in altering Scn3a expression during postnatal development and seizure condition.

  19. 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

  20. 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

  1. 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

  2. Nav1.1 modulation by a novel triazole compound attenuates epileptic seizures in rodents.

    PubMed

    Gilchrist, John; Dutton, Stacey; Diaz-Bustamante, Marcelo; McPherson, Annie; Olivares, Nicolas; Kalia, Jeet; Escayg, Andrew; Bosmans, Frank

    2014-05-16

    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

  3. 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

  4. All together now: Analogies between chimera state collapses and epileptic seizures.

    PubMed

    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.

  5. 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

  6. 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.

  7. Spatial characterization of interictal high frequency oscillations in epileptic neocortex

    PubMed Central

    Trevelyan, A. J.; Schroeder, C. E.; Goodman, R. R.; McKhann, G.; Emerson, R. G.

    2009-01-01

    Interictal high frequency oscillations (HFOs), in particular those with frequency components in excess of 200 Hz, have been proposed as important biomarkers of epileptic cortex as well as the genesis of seizures. We investigated the spatial extent, classification and distribution of HFOs using a dense 4 × 4 mm2 two dimensional microelectrode array implanted in the neocortex of four patients undergoing epilepsy surgery. The majority (97%) of oscillations detected included fast ripples and were concentrated in relatively few recording sites. While most HFOs were limited to single channels, ∼10% occurred on a larger spatial scale with simultaneous but morphologically distinct detections in multiple channels. Eighty per cent of these large-scale events were associated with interictal epileptiform discharges. We propose that large-scale HFOs, rather than the more frequent highly focal events, are the substrates of the HFOs detected by clinical depth electrodes. This feature was prominent in three patients but rarely seen in only one patient recorded outside epileptogenic cortex. Additionally, we found that HFOs were commonly associated with widespread interictal epileptiform discharges but not with locally generated ‘microdischarges’. Our observations raise the possibility that, rather than being initiators of epileptiform activity, fast ripples may be markers of a secondary local response. PMID:19745024

  8. 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.

  9. 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

  10. 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

  11. Neuronal avalanches, epileptic quakes and other transient forms of neurodynamics.

    PubMed

    Milton, John G

    2012-07-01

    Power-law behaviors in brain activity in healthy animals, in the form of neuronal avalanches, potentially benefit the computational activities of the brain, including information storage, transmission and processing. In contrast, power-law behaviors associated with seizures, in the form of epileptic quakes, potentially interfere with the brain's computational activities. This review draws attention to the potential roles played by homeostatic mechanisms and multistable time-delayed recurrent inhibitory loops in the generation of power-law phenomena. Moreover, it is suggested that distinctions between health and disease are scale-dependent. In other words, what is abnormal and defines disease it is not the propagation of neural activity but the propagation of activity in a neural population that is large enough to interfere with the normal activities of the brain. From this point of view, epilepsy is a disease that results from a failure of mechanisms, possibly located in part in the cortex itself or in the deep brain nuclei and brainstem, which truncate or otherwise confine the spatiotemporal scales of these power-law phenomena.

  12. 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

  13. Autobiographical amnesia and accelerated forgetting in transient epileptic amnesia

    PubMed Central

    Manes, F; Graham, K; Zeman, A; de Lujan, Calcagno M; Hodges, J

    2005-01-01

    Background: Recurrent brief isolated episodes of amnesia associated with epileptiform discharges on EEG recordings have been interpreted as a distinct entity termed transient epileptic amnesia (TEA). Patients with TEA often complain of autobiographical amnesia for recent and remote events, but show normal anterograde memory. Objective: To investigate (a) accelerated long term forgetting and (b) autobiographical memory in a group of patients with TEA. Methods: Seven patients with TEA and seven age matched controls were evaluated on a range of anterograde memory tasks in two sessions separated by 6 weeks and by the Galton-Crovitz test of cued autobiographical memory. Results: Patients with TEA showed abnormal long term forgetting of verbal material, with virtually no recall after 6 weeks. In addition, there was impaired recall of autobiographical memories from the time periods 1985–89 and 1990–94 but not from 1995–1999. Conclusions: TEA is associated with accelerated loss of new information and impaired remote autobiographical memory. There are a number of possible explanations including ongoing subclinical ictal activity, medial temporal lobe damage as a result of seizure, or subtle ischaemic pathology. Future analyses should seek to clarify the relationship between aetiology, seizure frequency, and degree of memory impairment. PMID:16170082

  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. Projecting memories: the role of the hippocampus in emotional mentalizing.

    PubMed

    Perry, D; Hendler, T; Shamay-Tsoory, S G

    2011-01-15

    Humans have a striking tendency to use past autobiographical events to understand their own behavior. However, it is unknown if we use our own memories to understand others. To assess the role of autobiographical memory in mentalizing we examined the contribution of memory structures, specifically the hippocampus, to emotional judgment of others. Subjects were scanned while making emotional judgments regarding themselves, and protagonists deemed similar to or dissimilar from themselves. Results indicated a significant correlation between rating of the self and the similar protagonists, particularly for the events subjects recalled from their past. Furthermore, we found an interaction between similarity and recollection so that only for events subjects recalled from their past, the hippocampus reacted differently for judgments regarding the self versus dissimilar others, but not for self versus similar others. These results suggest that people actually use their own repertoire of memories and project internal self knowledge while making emotional judgments regarding others. It is speculated that mentalizing is modulated by memories of similar past events and depends on the protagonist we face. PMID:20817106

  16. Age-related changes in the rat hippocampus.

    PubMed

    Is, Merih; Comunoglu, Nil Ustundag; Comunoglu, Cem; Eren, Bulent; Ekici, Isin Dogan; Ozkan, Ferda

    2008-05-01

    The human brain is uniquely powerful in its cognitive abilities, yet the hippocampal and neocortical circuits that mediate these complex functions are highly vulnerable during aging. In this study, we analyzed age-related changes in the rat hippocampus by studying newborn (1 month), middle-aged (12 months), and older (24 months) male and female Sprague-Dawley rats. We evaluated neuronal dystrophy, neuron scattering, and granulovacuolar degeneration in the hippocampal area using light microscopy, according to age and gender. We detected significant neuronal dystrophy in the CA1, CA2, and CA3 areas in male rats, and in the CA1, CA3, and CA4 areas in female rats. Degenerative changes, indicated by neuron scattering, were observed in the CA1, CA2, and CA3 areas of male and the CA2 and CA4 areas of female rats. Changes in all areas of the hippocampus were observed with increasing age; these changes included neuronal dystrophy and neuron scattering and did not differ significantly between male and female rats.

  17. THEORETICAL REVIEW The Hippocampus, Time, and Memory Across Scales

    PubMed Central

    Howard, Marc W.; Eichenbaum, Howard

    2014-01-01

    A wealth of experimental studies with animals have offered insights about how neural networks within the hippocampus support the temporal organization of memories. These studies have revealed the existence of “time cells” that encode moments in time, much as the well-known “place cells” map locations in space. Another line of work inspired by human behavioral studies suggests that episodic memories are mediated by a state of temporal context that changes gradually over long time scales, up to at least a few thousand seconds. In this view, the “mental time travel” hypothesized to support the experience of episodic memory corresponds to a “jump back in time” in which a previous state of temporal context is recovered. We suggest that these 2 sets of findings could be different facets of a representation of temporal history that maintains a record at the last few thousand seconds of experience. The ability to represent long time scales comes at the cost of discarding precise information about when a stimulus was experienced—this uncertainty becomes greater for events further in the past. We review recent computational work that describes a mechanism that could construct such a scale-invariant representation. Taken as a whole, this suggests the hippocampus plays its role in multiple aspects of cognition by representing events embedded in a general spatiotemporal context. The representation of internal time can be useful across nonhippocampal memory systems. PMID:23915126

  18. 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

  19. 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.

  20. Reevaluating the Role of the Hippocampus in Delay Eyeblink Conditioning

    PubMed Central

    Hu, Bo; Zhang, Hui-ming; Li, Yi-ding; Li, Xuan; Li, Qiong; Sui, Jian-feng

    2013-01-01

    The role of the hippocampus in delay eyeblink conditioning (DEC) remains controversial. Here, we investigated the involvement of the hippocampus in DEC with a soft tone as the conditioned stimulus (CS) by using electrolytic lesions or muscimol inactivation of guinea pig dorsal hippocampus. Interestingly, when a soft tone was used as a CS, electrolytic lesions of the hippocampus significantly retarded acquisition of the conditioned response (CR), and muscimol infusions into hippocampus distinctly inhibited the acquisition and expression of CR, but had no significant effect on consolidation of well-learned CR. In contrast, both electrolytic lesions and muscimol inactivation of hippocampus produced no significant deficits in the CR when a loud tone was used as the CS. These results demonstrate that the hippocampus is essential for the DEC when the delay task was rendered more difficult. PMID:23951119

  1. Neuron to Astrocyte Communication via Cannabinoid Receptors Is Necessary for Sustained Epileptiform Activity in Rat Hippocampus

    PubMed Central

    Coiret, Guyllaume; Ster, Jeanne; Grewe, Benjamin; Wendling, Fabrice; Helmchen, Fritjof; Gerber, Urs; Benquet, Pascal

    2012-01-01

    Astrocytes are integral functional components of synapses, regulating transmission and plasticity. They have also been implicated in the pathogenesis of epilepsy, although their precise roles have not been comprehensively characterized. Astrocytes integrate activity from neighboring synapses by responding to neuronally released neurotransmitters such as glutamate and ATP. Strong activation of astrocytes mediated by these neurotransmitters can promote seizure-like activity by initiating a positive feedback loop that induces excessive neuronal discharge. Recent work has demonstrated that astrocytes express cannabinoid 1 (CB1) receptors, which are sensitive to endocannabinoids released by nearby pyramidal cells. In this study, we tested whether this mechanism also contributes to epileptiform activity. In a model of 4-aminopyridine induced epileptic-like activity in hippocampal slice cultures, we show that pharmacological blockade of astrocyte CB1 receptors did not modify the initiation, but significantly reduced the maintenance of epileptiform discharge. When communication in astrocytic networks was disrupted by chelating astrocytic calcium, this CB1 receptor-mediated modulation of epileptiform activity was no longer observed. Thus, endocannabinoid signaling from neurons to astrocytes represents an additional significant factor in the maintenance of epileptiform activity in the hippocampus. PMID:22615976

  2. Early-onset acquired epileptic aphasia (Landau-Kleffner syndrome, LKS) and regressive autistic disorders with epileptic EEG abnormalities: the continuing debate.

    PubMed

    Deonna, Thierry; Roulet-Perez, Eliane

    2010-10-01

    Early-onset acquired epileptic aphasia (Landau-Kleffner syndrome) may present as a developmental language disturbance and the affected child may also exhibit autistic features. Landau-Kleffner is now seen as the rare and severe end of a spectrum of cognitive-behavioural symptoms that can be seen in idiopathic (genetic) focal epilepsies of childhood, the benign end being the more frequent typical rolandic epilepsy. Several recent studies show that many children with rolandic epilepsy have minor developmental cognitive and behavioural problems and that some undergo a deterioration (usually temporary) in these domains, the so-called "atypical" forms of the syndrome. The severity and type of deterioration correlate with the site and spread of the epileptic spikes recorded on the electroencephalogram within the perisylvian region, and continuous spike-waves during sleep (CSWS) frequently occur during this period of the epileptic disorder. Some of these children have more severe preexisting communicative and language developmental disorders. If early stagnation or regression occurs in these domains, it presumably reflects epileptic activity in networks outside the perisylvian area, i.e. those involved in social cognition and emotions. Longitudinal studies will be necessary to find out if and how much the bioelectrical abnormalities play a causal role in these subgroup of children with both various degrees of language and autistic regression and features of idiopathic focal epilepsy. One has to remember that it took nearly 40 years to fully acknowledge the epileptic origin of aphasia in Landau-Kleffner syndrome and the milder acquired cognitive problems in rolandic epilepsies.

  3. 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.

  4. [HIPPOCAMPUS AS AN ORGANIZER OF RESENT ATTENTION].

    PubMed

    Serkova, V V; Nikolskaya, K A; Eremina, L V

    2015-06-01

    The damage of dorsal hippocampus in mice F1 from DBA/2J and C57BL/6J on the learning in conditions of free choice in a complex multialternative maze was studied. It was revealed that the HPC-mice were able to form a 4-links food-getting habit in the cyclic form. The main differences affected the conjugation of the investigate activity, behavioral efficiency and inhibition of mistakes. While these processes developed by the same exponential types in control, this conjugation were absent in HPC-mice. The main defects were found in stage of habit stabilization: motivational state stability reduced sharply and duration of transition from disorganization to organizing behavior increased. It is supposed that the hippocampus involved in learning and memory indirectly because its main role is organization of the dominant state providing the stability of attention for habit realization.

  5. Environmental enrichment restores CA1 hippocampal LTP and reduces severity of seizures in epileptic mice.

    PubMed

    Morelli, Emanuela; Ghiglieri, Veronica; Pendolino, Valentina; Bagetta, Vincenza; Pignataro, Annabella; Fejtova, Anna; Costa, Cinzia; Ammassari-Teule, Martine; Gundelfinger, Eckart D; Picconi, Barbara; Calabresi, Paolo

    2014-11-01

    We have analyzed the effects of environmental enrichment (EE) in a seizure-prone mouse model in which the genetic disruption of the presynaptic protein Bassoon leads to structural and functional alterations in the hippocampus and causes early spontaneous seizures mimicking human neurodevelopmental disorders. One-month EE starting at P21 reduced seizure severity, preserved long-term potentiation (LTP) and paired-pulse synaptic responses in the hippocampal CA1 neuronal population and prevented the reduction of spine density and dendrite branching of pyramidal neurons. These data demonstrate that EE exerts its therapeutic effect by normalizing multiple aspects of hippocampal function and provide experimental support for its use in the optimization of existent treatments.

  6. How does the hippocampus contribute to memory?

    PubMed

    Eichenbaum, Howard

    2003-10-01

    Recently, Wirth et al. reported that hippocampal neurons signal the acquisition of new associations by altering the selectivity of their responses to crucial stimuli. The course of these changes was gradual, with some neurons recruited before, others at the time of, and yet others shortly after learning. These observations suggest the hippocampus might contribute to memory by identifying consistencies across experiences that constitute important new associations.

  7. Time and space in the hippocampus.

    PubMed

    Howard, Marc W; Eichenbaum, Howard

    2015-09-24

    It has been hypothesized that one of the functions of the hippocampus is to enable the learning of relationships between different stimuli experienced in the environment. These relationships might be spatial ("the bathroom is about 5m down the hall from the bedroom") or temporal ("the coffee is ready about 3 min after the button was pressed"). Critically, these spatial and temporal relationships may exist on a variety of scales from a few hundred milliseconds up to minutes. In order to learn consistent relationships between stimuli separated by a variety of spatial and temporal scales using synaptic plasticity that has a fixed temporal window extending at most a few hundred milliseconds, information about the spatial and temporal relationships of distant stimuli must be available to the hippocampus in the present. Hippocampal place cells and time cells seem well suited to represent the spatial and temporal locations of distant stimuli in order to support learning of these relationships. We review a recent computational hypothesis that can be used to construct both spatial and temporal relationships. We suggest that there is a deep computational connection between spatial and temporal coding in the hippocampus and that both serve the overarching function of learning relationships between stimuli-constructing a "memory space." This article is part of a Special Issue entitled SI: Brain and Memory.

  8. Serodiagnosis of neurocysticercosis in patients with epileptic seizure using ELISA and immunoblot assay.

    PubMed

    Ishida, Maria M I; Peralta, Regina Helena S; Livramento, José A; Hoshino-Shimizu, Sumie; Peralta, José M; Vaz, Adelaide J

    2006-01-01

    Sera from 88 patients from Santa Catarina and São Paulo states of Brazil, with epileptic seizures who underwent cerebral computed tomography (CT) were analyzed for the detection of antibodies to T. solium cysticercus by ELISA and Immunoblot (IB) with the following antigens: Taenia solium cysticercus total saline (Tso), Taenia crassiceps cysticercus vesicular fluid (Tcra-vf) and T. crassiceps cysticercus glycoproteins (Tcra-gp). ELISA carried out with Tso, Tcra-vf and Tcra-gp antigens showed 95%, 90% and 80% sensitivities, respectively, and 68%, 85% and 93% specificities, respectively. In the epileptic patients group, ELISA positivity was 30%, 51% and 35% with Tso, Tcra-vf and Tcra-gp antigens respectively. Considering the IB as the confirmatory test, the positivity was 16% (14/88) in the epileptic patients total group and 22% (12/54) in the epileptic patients with positive CT and signals of cysticercosis. We found a significant statistical correlation among ELISA or IB results and the phase of the disease when any antigens were used (p < 0.05). We emphasize the need to introduce in the laboratory routine the search for neurocysticercosis (NC) in patients presenting with epileptic seizures because of the high risk of acquiring NC in our region and its potential cause of epilepsy.

  9. 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

  10. 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

  11. Startle provoked epileptic seizures:features in 19 patients.

    PubMed Central

    Manford, M R; Fish, D R; Shorvon, S D

    1996-01-01

    OBJECTIVES--To define the clinical characteristics of a group of patients with startle provoked epileptic seizures (SPES). METHODS--Nineteen patients were identified during the course of a larger study of clinical seizure patterns. A witnessed seizure account was obtained in all patients; interictal EEG in 18, video-EEG-telemetry in eight, CT in 18, and high resolution MRI in eight. RESULTS--The onset of SPES was in childhood or adolescence in 14 of 19 patients. It was preceded by exclusively spontaneous seizures in nine patients and SPES had been replaced by exclusively spontaneous seizures in two patients. Sudden noise was the main triggering stimulus and somatosensory and visual stimuli were also effective in some patients. The clinical seizure pattern involved asymmetric tonic posturing in 16 of 19 patients. Focal neurological signs were present in nine patients, mental retardation in six, and 10 were clinically normal. Ictal scalp EEG showed a clear seizure discharge in only one patient with a tonic seizure pattern; over the lateral frontal electrodes contralateral to the posturing limbs. Brain CT showed a porencephalic cyst in three patients, focal frontal atrophy in one, and generalised atrophy in one. Brain MRI was undertaken in five normal subjects and three neurologically impaired patients, six with normal CT. It showed a porencephalic cyst in one patient. In six patients, there were dysplastic lesions. They affected the lateral premotor cortex in three patients and the perisylvian cortex in three patients, one with bilateral perisylvian abnormality. CONCLUSIONS--SPES are more frequent than is generally appreciated. They may be transient and occur relatively commonly without fixed deficit, by contrast with previous reports. The imaging abnormalities identified in those without diffuse cerebral damage suggest that SPES are often due to occult congenital lesions and that the lateral premotor and perisylvian cortices are important in this phenomenon. Images

  12. Fear as the main feature of epileptic seizures

    PubMed Central

    Biraben, A; Taussig, D; Thomas, P; Even, C; Vignal, J; Scarabin, J; Chauvel, P

    2001-01-01

    OBJECTIVES—There are circumstances in which partial seizures may be misdiagnosed as acute psychiatric disturbances. In particular, when fear is the prominent feature the patient may be considered for years as having panic attacks. Eight patients in whom fear was the main symptom of the seizures are reported on. Patients who had a proved lack of consciousness during the fits and patients in whom fear was just fear of having a seizure were excluded. The ictal involvement of temporal limbic and frontal structures in those patients with fear of particular intensity was studied.
METHODS—The localisation of the epileptogenic zone was assessed by prolonged interictal EEG recordings as well as ictal video-EEG recording of at least one seizure in every patient; five had ictal SPECT and four had chronic stereotactic implantation of depth electrodes (SEEG). In six patients, a cortical resection was performed with an Engel's class 1 outcome (minimum 28 months follow up, except for two patients).
RESULTS—Localisations of primary epileptogenic zones were right temporal in three patients, left temporal in three, bitemporal in one, and frontal in one. In all cases, diagnosis of epileptic seizures could be clinically evoked because of the stereotypy of fits and of associated symptoms. The association of a fear sensation, autonomic symptoms, and coordinated behaviour suggests disturbance of a particular system. The SEEG data argue for temporolimbic and prefrontal lobe involvement in the expression of ictal fear.
CONCLUSIONS—In intense ictal fear, with coordinated behaviour and autonomic features, the discharge may involve or interfere with a physiological complex information processing network. This network involves orbitoprefrontal, anterior cingulate, and temporal limbic cortices.

 PMID:11160466

  13. 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.

  14. 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

  15. 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

  16. Effects of monotherapy and polytherapy on the blink reflex in epileptic patients.

    PubMed

    Lancman, M E; Cristiano, E; Golimstok, A; Granillo, R J

    1993-01-01

    We performed the blink reflex (BR) in 20 normal volunteers, 13 epileptic patients receiving antiepileptic drug (AED) monotherapy, and 13 epileptic patients receiving AED polytherapy. Comparison of R1, ipsilateral and contralateral R2 and VIIth nerve latencies in the three groups showed no statistically significant differences R1 and VIIth nerve latencies among the three groups. There were statistically significant differences between the polytherapy group and the monotherapy and control groups in comparisons of ipsilateral and contralateral R2. There were no significant differences between the monotherapy group and the control group for ipsilateral and contralateral R2. We hypothesized that AED polytherapy might interfere with synaptic transmission in the polysynaptic pathway of the blink reflex, prolonging the latency of R2. These results provide further evidence of the pathophysiologic effects associated with polytherapy in epileptic patients.

  17. 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.

  18. 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

  19. Long-term variability of global statistical properties of epileptic brain networks

    NASA Astrophysics Data System (ADS)

    Kuhnert, Marie-Therese; Elger, Christian E.; Lehnertz, Klaus

    2010-12-01

    We investigate the influence of various pathophysiologic and physiologic processes on global statistical properties of epileptic brain networks. We construct binary functional networks from long-term, multichannel electroencephalographic data recorded from 13 epilepsy patients, and the average shortest path length and the clustering coefficient serve as global statistical network characteristics. For time-resolved estimates of these characteristics we observe large fluctuations over time, however, with some periodic temporal structure. These fluctuations can—to a large extent—be attributed to daily rhythms while relevant aspects of the epileptic process contribute only marginally. Particularly, we could not observe clear cut changes in network states that can be regarded as predictive of an impending seizure. Our findings are of particular relevance for studies aiming at an improved understanding of the epileptic process with graph-theoretical approaches.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies.

    PubMed

    2014-10-01

    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.

  6. 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

  7. 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

  8. 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

  9. The seasonal hippocampus of food-storing birds.

    PubMed

    Sherry, David F; Hoshooley, Jennifer S

    2009-03-01

    Food storing is seasonal in birds like chickadees, nuthatches and jays, occurring at high levels in fall and winter and low levels in spring and summer. Memory for cache sites is hippocampus dependent in chickadees and both the recruitment of new neurons into the hippocampus and the total size of the hippocampus change seasonally. Unlike seasonal change in the vocal control nuclei of songbirds, however, change in the hippocampus appears not to be controlled by photoperiod. The annual timing of hippocampal neuronal recruitment and change in hippocampal size is quite variable, reaching maximum levels at different times of year in different studies. The amount of food-storing activity by chickadees is known to be influenced by flock dominance structure, energy balance, food availability, and other seasonally varying factors. The variable timing of seasonal change in the hippocampus may indicate that the hippocampus of food-storing birds changes annually in response to change in the intensity of food storing behaviour itself.

  10. Facilitation of epileptic activity during sleep is mediated by high amplitude slow waves.

    PubMed

    Frauscher, Birgit; von Ellenrieder, Nicolás; Ferrari-Marinho, Taissa; Avoli, Massimo; Dubeau, François; Gotman, Jean

    2015-06-01

    Epileptic discharges in focal epilepsy are frequently activated during non-rapid eye movement sleep. Sleep slow waves are present during this stage and have been shown to include a deactivated ('down', hyperpolarized) and an activated state ('up', depolarized). The 'up' state enhances physiological rhythms, and we hypothesize that sleep slow waves and particularly the 'up' state are the specific components of non-rapid eye movement sleep that mediate the activation of epileptic activity. We investigated eight patients with pharmaco-resistant focal epilepsies who underwent combined scalp-intracerebral electroencephalography for diagnostic evaluation. We analysed 259 frontal electroencephalographic channels, and manually marked 442 epileptic spikes and 8487 high frequency oscillations during high amplitude widespread slow waves, and during matched control segments with low amplitude widespread slow waves, non-widespread slow waves or no slow waves selected during the same sleep stages (total duration of slow wave and control segments: 49 min each). During the slow waves, spikes and high frequency oscillations were more frequent than during control segments (79% of spikes during slow waves and 65% of high frequency oscillations, both P ∼ 0). The spike and high frequency oscillation density also increased for higher amplitude slow waves. We compared the density of spikes and high frequency oscillations between the 'up' and 'down' states. Spike and high frequency oscillation density was highest during the transition from the 'up' to the 'down' state. Interestingly, high frequency oscillations in channels with normal activity expressed a different peak at the transition from the 'down' to the 'up' state. These results show that the apparent activation of epileptic discharges by non-rapid eye movement sleep is not a state-dependent phenomenon but is predominantly associated with specific events, the high amplitude widespread slow waves that are frequent, but not

  11. 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.

  12. 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.

  13. Late-diagnosed bilateral intertrochanteric femur fracture during an epileptic seizure.

    PubMed

    Copuroğlu, Cem; Ozcan, Mert; Dülger, Hakan; Yalnız, Erol

    2012-01-01

    Although spontaneous and simultaneous bilateral hip fractures without trauma are seen rarely, epileptic seizures may lead to these fractures. We present an 82-year-old female patient with poor bone quality and a 20-year history of epilepsy. She had been using anticonvulsant drugs for almost 20 years. Following a convulsive epileptic attack, bilateral intertrochanteric femur fractures occurred (causing bilateral hip pain), which was diagnosed on the 12th day. An earlier pelvic anteroposterior roentgenogram would be helpful for early diagnosis. It should not be forgotten that bone fractures may be observed without trauma in epilepsy patients.

  14. 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

  15. 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

  16. 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

  17. 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

  18. Equivalent activation of the hippocampus by face-face and face-laugh paired associate learning and recognition.

    PubMed

    Holdstock, J S; Crane, J; Bachorowski, J-A; Milner, B

    2010-11-01

    The human hippocampus is known to play an important role in relational memory. Both patient lesion studies and functional-imaging studies have shown that it is involved in the encoding and retrieval from memory of arbitrary associations. Two recent patient lesion studies, however, have found dissociations between spared and impaired memory within the domain of relational memory. Recognition of associations between information of the same kind (e.g., two faces) was spared, whereas recognition of associations between information of different kinds (e.g., face-name or face-voice associations) was impaired by hippocampal lesions. Thus, recognition of associations between information of the same kind may not be mediated by the hippocampus. Few imaging studies have directly compared activation at encoding and recognition of associations between same and different types of information. Those that have have shown mixed findings and been open to alternative interpretation. We used fMRI to compare hippocampal activation while participants studied and later recognized face-face and face-laugh paired associates. We found no differences in hippocampal activation between our two types of stimulus materials during either study or recognition. Study of both types of paired associate activated the hippocampus bilaterally, but the hippocampus was not activated by either condition during recognition. Our findings suggest that the human hippocampus is normally engaged to a similar extent by study and recognition of associations between information of the same kind and associations between information of different kinds.

  19. Network dynamics of the brain and influence of the epileptic seizure onset zone

    PubMed Central

    Burns, Samuel P.; Santaniello, Sabato; Yaffe, Robert B.; Jouny, Christophe C.; Crone, Nathan E.; Bergey, Gregory K.; Anderson, William S.; Sarma, Sridevi V.

    2014-01-01

    The human brain is a dynamic networked system. Patients with partial epileptic seizures have focal regions that periodically diverge from normal brain network dynamics during seizures. We studied the evolution of brain connectivity before, during, and after seizures with graph-theoretic techniques on continuous electrocorticographic (ECoG) recordings (5.4 ± 1.7 d per patient, mean ± SD) from 12 patients with temporal, occipital, or frontal lobe partial onset seizures. Each electrode was considered a node in a graph, and edges between pairs of nodes were weighted by their coherence within a frequency band. The leading eigenvector of the connectivity matrix, which captures network structure, was tracked over time and clustered to uncover a finite set of brain network states. Across patients, we found that (i) the network connectivity is structured and defines a finite set of brain states, (ii) seizures are characterized by a consistent sequence of states, (iii) a subset of nodes is isolated from the network at seizure onset and becomes more connected with the network toward seizure termination, and (iv) the isolated nodes may identify the seizure onset zone with high specificity and sensitivity. To localize a seizure, clinicians visually inspect seizures recorded from multiple intracranial electrode contacts, a time-consuming process that may not always result in definitive localization. We show that network metrics computed from all ECoG channels capture the dynamics of the seizure onset zone as it diverges from normal overall network structure. This suggests that a state space model can be used to help localize the seizure onset zone in ECoG recordings. PMID:25404339

  20. Overnight Sleep Enhances Hippocampus-Dependent Aspects of Spatial Memory

    PubMed Central

    Nguyen, Nam D.; Tucker, Matthew A.; Stickgold, Robert; Wamsley, Erin J.

    2013-01-01

    Study Objectives: Several studies have now demonstrated that spatial information is processed during sleep, and that posttraining sleep is beneficial for human navigation. However, it remains unclear whether the effects of sleep are primarily due to consolidation of cognitive maps, or alternatively, whether sleep might also affect nonhippocampal aspects of navigation (e.g., speed of motion) involved in moving through a virtual environment. Design: Participants were trained on a virtual maze navigation task (VMT) and then given a memory test following either a day of wakefulness or a night of sleep. Subjects reported to the laboratory for training at either 10:00am or 10:00pm, depending on randomly assigned condition, and were tested 11 h later. Overnight subjects slept in the laboratory with polysomnography. Setting: A hospital-based academic sleep laboratory. Patients or Participants: Thirty healthy college student volunteers. Interventions: N/A. Measurements and Results: Point-by-point position data were collected from the VMT. Analysis of the movement data revealed a sleep-dependent improvement in maze completion time (P < 0.001) due to improved spatial understanding of the maze layout, which led to a shortening of path from start to finish (P = 0.01) rather than faster exploration speed through the maze (P = 0.7). Conclusions: We found that overnight sleep benefitted performance, not because subjects moved faster through the maze, but because they were more accurate in navigating to the goal. These findings suggest that sleep enhances participants' knowledge of the spatial layout of the maze, contributing to the consolidation of hippocampus-dependent spatial information. Citation: Nguyen ND; Tucker MA; Stickgold R; Wamsley EJ. Overnight sleep enhances hippocampus-dependent aspects of spatial memory. SLEEP 2013;36(7):1051-1057. PMID:23814342

  1. Ulinastatin inhibits cerebral ischemia-induced apoptosis in the hippocampus of gerbils

    PubMed Central

    CHO, YOUNG-SAM; SHIN, MAL-SOON; KO, IL-GYU; KIM, SUNG-EUN; KIM, CHANG-JU; SUNG, YUN-HEE; YOON, HYE-SUN; LEE, BONG-JAE

    2015-01-01

    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

  2. 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.

  3. Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior

    PubMed Central

    Mineur, Yann S.; Obayemi, Adetokunbo; Wigestrand, Mattis B.; Fote, Gianna M.; Calarco, Cali A.; Li, Alice M.; Picciotto, Marina R.

    2013-01-01

    Symptoms of depression can be induced in humans through blockade of acetylcholinesterase (AChE) whereas antidepressant-like effects can be produced in animal models and some clinical trials by limiting activity of acetylcholine (ACh) receptors. Thus, ACh signaling could contribute to the etiology of mood regulation. To test this hypothesis, we administered the AChE inhibitor physostigmine to mice and demonstrated an increase in anxiety- and depression-like behaviors that was reversed by administration of nicotinic or muscarinic antagonists. The behavioral effects of physostigmine were also reversed by administration of the selective serotonin reuptake inhibitor fluoxetine. Administration of fluoxetine also increased AChE activity throughout the brain, with the greatest change in the hippocampus. To determine whether cholinergic signaling in the hippocampus could contribute to the systemic effects of cholinergic drugs, we infused physostigmine or virally delivered shRNAs targeting AChE into the hippocampus. Both pharmacological and molecular genetic decreases in hippocampal AChE activity increased anxiety- and depression-like behaviors and decreased resilience to repeated stress in a social defeat paradigm. The behavioral changes due to shRNA-mediated knockdown of AChE were rescued by coinfusion of an shRNA-resistant AChE transgene into the hippocampus and reversed by systemic administration of fluoxetine. These data demonstrate that ACh signaling in the hippocampus promotes behaviors related to anxiety and depression. The sensitivity of these effects to fluoxetine suggests that shRNA-mediated knockdown of hippocampal AChE represents a model for anxiety- and depression-like phenotypes. Furthermore, abnormalities in the cholinergic system may be critical for the etiology of mood disorders and could represent an endophenotype of depression. PMID:23401542

  4. Context learning in the rodent hippocampus.

    PubMed

    Fuhs, Mark C; Touretzky, David S

    2007-12-01

    We present a Bayesian statistical theory of context learning in the rodent hippocampus. While context is often defined in an experimental setting in relation to specific background cues or task demands, we advance a single, more general notion of context that suffices for a variety of learning phenomena. Specifically, a context is defined as a statistically stationary distribution of experiences, and context learning is defined as the problem of how to form contexts out of groups of experiences that cluster together in time. The challenge of context learning is solving the model selection problem: How many contexts make up the rodent's world? Solving this problem requires balancing two opposing goals: minimize the variability of the distribution of experiences within a context and minimize the likelihood of transitioning between contexts. The theory provides an understanding of why hippocampal place cell remapping sometimes develops gradually over many days of experience and why even consistent landmark differences may need to be relearned after other environmental changes. The theory provides an explanation for progressive performance improvements in serial reversal learning, based on a clear dissociation between the incremental process of context learning and the relatively abrupt context selection process. The impact of partial reinforcement on reversal learning is also addressed. Finally, the theory explains why alternating sequence learning does not consistently result in unique context-dependent sequence representations in hippocampus.

  5. Object recognition memory and the rodent hippocampus.

    PubMed

    Broadbent, Nicola J; Gaskin, Stephane; Squire, Larry R; Clark, Robert E

    2010-01-01

    In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR task. Rats received 12 5-min exposures to two identical objects and then received either bilateral lesions of the hippocampus or sham surgery 1 d, 4 wk, or 8 wk after the final exposure. On a retention test 2 wk after surgery, the 1-d and 4-wk hippocampal lesion groups exhibited impaired object recognition memory. In contrast, the 8-wk hippocampal lesion group performed similarly to controls, and both groups exhibited a preference for the novel object. These same rats were then given four postoperative tests using unique object pairs and a 3-h delay between the exposure phase and the test phase. Hippocampal lesions produced moderate and reliable memory impairment. The results suggest that the hippocampus is important for object recognition memory.

  6. Food storing and the hippocampus in Paridae.

    PubMed

    Healy, S D; Krebs, J R

    1996-01-01

    Food storing passerines have a larger hippocampus, relative to the rest of the telencephalon and/or body mass, than do non-storing species. This study looked at the relationship between relative size of the hippocampus and degree of food storing in six species of Paridae (blue tit, Parus caeruleus, great tit, P major, marsh tit, P palustris, coal tit, P ater, black-capped chickadee, P. atricapillus, and willow tit, P montanus). The degree of storing by these species varies from little or none to thousands of food items. The period over which food is stored also varies from a few hours to several months. The results showed that hippocampal volume, relative to the rest of the telencephalon, is larger in those species that store more food, store for longer, or both. In an analysis of intraspecific variation within two of the species, the food storing marsh tit and the non-storing blue tit, there was a significant positive relationship between hippocampal volume relative to body mass, and telencephalic volume relative to body mass, in the marsh tit but no relationship between these variables in the blue tit.

  7. The role of antiepileptic drugs in free radicals generation and antioxidant levels in epileptic patients.

    PubMed

    Eldin, Essam Eldin Mohamed Nour; Elshebiny, Hosam Abdel-Fattah; Mohamed, Tarek Mostafa; Abdel-Aziz, Mohamed Abdel-Azim; El-Readi, Mahmoud Zaki

    2016-01-01

    Many risk factors are encountered during the pathogenesis of epilepsy. In this study, the effect of seizure frequency on free radical generation and antioxidants levels in epileptic patients was evaluated. This study was carried out on 15 healthy controls (GI) and 60 epileptic patients treated with mono- or poly-therapy of carbamazepine, valproic acid, or phenytoin. The treated epileptic patients were divided into 2 main groups according to the seizure frequency: controlled seizure patients GII (n = 30) and uncontrolled seizure patients GIII (n = 30). GII included the GIIA subgroup (n = 15) which had been seizure free for more than 12 months and the GIIB subgroup (n = 15) which had been seizure free for a period from 6 to12 months. GIII included GIIIA (n = 15) and GIIIB (n = 15) for patients which had a seizure frequency of less than and more than four times/month, respectively. In comparison to the control group (GI), the levels of nitric oxide (NO) and malondialdehyde/creatinine ratio were significantly increased in GIIB, GIIIA, and GIIIB, while vitamins A and E levels were significantly decreased in GIIIB. Serum NO levels had significant negative correlations with serum vitamin E in the GIIA and GIIB groups, and with vitamin A in the GIIIA and GIIIB groups. However, serum NO had positive correlation with urinary MDA/Cr ratio. The imbalance between free radical generation and antioxidant system in epileptic patients may be a factor in seizure frequency.

  8. Inflammation and endothelium response in epileptic patients: A case-control study

    PubMed Central

    Farhang, Amir; Javanmard, Saghayegh Haghjooy; Mehvari, Jafar; Zare, Mohammad; Saadatnia, Mohammad

    2016-01-01

    Background: Blood brain barrier (BBB) permeability plays an important role in the brain impairments. The barrier is composed of endothelium cells, due to the presence of tight junctions that connect endothelium cells. The failure of BBB function has triggering chronic or acute seizures through brain inflammation and BBB permeability. Seizure induces vasodilation, BBB leakage and up-regulation of vascular cell adhesion molecules which able to bind integrins blood leukocytes. Materials and Methods: In this case-control study we included 40 epileptic patients who were sampled during a seizure as a case group and 20 healthy subjects as a healthy control group. Plasma levels of the inflammation and endothelium markers including intercellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), interleukin 1 beta (IL-1β) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assays (ELISAs). Results: The ICAM and VCAM concentration in the epileptic patients (135.8 ± 5.35) (52.04 ± 4.24) were significantly higher than healthy control group (110.32 ± 5.04) (23.38 ± 3.01) (P < 0.005). IL-1 beta concentration was not significantly different between groups (P = 0.594). However, CRP level was significantly up-regulated in epileptic patients (P < 0.005). Conclusion: Epileptic patients have BBB leakage and dysfunction as the up-regulation of the endothelium cytokines showed. The BBB leakage may be the result of the inflammatory impairment.

  9. Mozart K.545 Mimics Mozart K.448 in Reducing Epileptiform Discharges in Epileptic Children

    PubMed Central

    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

  10. 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…

  11. 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…

  12. Two epileptic syndromes, one brain: childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes.

    PubMed

    Cerminara, Caterina; Coniglio, Antonella; El-Malhany, Nadia; Casarelli, Livia; Curatolo, Paolo

    2012-01-01

    Childhood absence epilepsy (CAE) and benign childhood epilepsy with centrotemporal spikes (BCECTS), or benign rolandic epilepsy (BRE), are the most common forms of childhood epilepsy. CAE and BCECTS are well-known and clearly defined syndromes; although they are strongly dissimilar in terms of their pathophysiology, these functional epileptic disturbances share many features such as similar age at onset, overall good prognosis, and inheritance factors. Few reports are available on the concomitance of CAE and BCECTS in the same patients or the later occurrence of generalized epilepsy in patients with a history of partial epilepsy. In most cases described in the literature, absence seizures always started after the onset of benign focal epilepsy but the contrary has never occurred yet. We describe two patients affected by idiopathic generalized epileptic syndrome with typical absences, who experienced BCECTS after remission of seizures and normalization of EEG recordings. While the coexistence of different seizure types within an epileptic syndrome is not uncommon, the occurrence of childhood absence and BCECTS in the same child appears to be extremely rare, and this extraordinary event supports the hypothesis that CAE and BCECTS are two distinct epileptic conditions. However, recent interesting observations in animal models suggest that BCECTS and CAE could be pathophysiologically related and that genetic links could play a large role.

  13. Possible reasons why certain epileptics commit unlawful acts during or directly after seizures.

    PubMed

    van Rensburg, P H; Gagiano, C A; Verschoor, T

    1994-01-01

    Courts have accepted that epileptics sometimes commit unlawful acts as a result of an epileptic seizure. Reasons for this unlawful behaviour may be found in the interictal, ictal and post-ictal phases of the seizure. Interictal aspects which are relevant to the form of epileptic automatism may be the person's natural tendencies, the same psychodynamic factors which determine the contents of dreams, the person's social background of violence and the contents of a person's thoughts immediately before a seizure. Ictal aspects include the specific part of the brain from which the seizure originates, the loss of integration of incoming sensorial stimuli with motor-emotional output, the loss of higher control associated with a reversion to primitive automatic behaviour and the emergence of repressed feelings and aggressive instincts. Post-ictal violent behaviour may stem from the epileptic's misinterpretation of well-meant attempts by bystanders to protect him or her against the consequences of his or her confused conduct--and is usually characterized by a clouded consciousness, paranoid ideas and hallucinations.

  14. 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)

  15. 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.

  16. Eight to Twelve Hertz Occipital EEG Training with Moderate and Severely Retarded Epileptic Individuals.

    ERIC Educational Resources Information Center

    Rudrud, Eric; Striefel, Sebastian

    1981-01-01

    Three retarded epileptic individuals (17 to 22 years old) with a variety of seizure disorders were provided with 8 to 12 Hz occipital EEG biofeedback training. While seizures were not totally eliminated in any of the Ss, the results of the study indicated that all Ss exhibited decreases in some aspect of their seizure activity. (Author)

  17. Inflammation and endothelium response in epileptic patients: A case-control study

    PubMed Central

    Farhang, Amir; Javanmard, Saghayegh Haghjooy; Mehvari, Jafar; Zare, Mohammad; Saadatnia, Mohammad

    2016-01-01

    Background: Blood brain barrier (BBB) permeability plays an important role in the brain impairments. The barrier is composed of endothelium cells, due to the presence of tight junctions that connect endothelium cells. The failure of BBB function has triggering chronic or acute seizures through brain inflammation and BBB permeability. Seizure induces vasodilation, BBB leakage and up-regulation of vascular cell adhesion molecules which able to bind integrins blood leukocytes. Materials and Methods: In this case-control study we included 40 epileptic patients who were sampled during a seizure as a case group and 20 healthy subjects as a healthy control group. Plasma levels of the inflammation and endothelium markers including intercellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), interleukin 1 beta (IL-1β) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assays (ELISAs). Results: The ICAM and VCAM concentration in the epileptic patients (135.8 ± 5.35) (52.04 ± 4.24) were significantly higher than healthy control group (110.32 ± 5.04) (23.38 ± 3.01) (P < 0.005). IL-1 beta concentration was not significantly different between groups (P = 0.594). However, CRP level was significantly up-regulated in epileptic patients (P < 0.005). Conclusion: Epileptic patients have BBB leakage and dysfunction as the up-regulation of the endothelium cytokines showed. The BBB leakage may be the result of the inflammatory impairment. PMID:27656600

  18. [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.

  19. The anterior hippocampus supports a coarse, global environmental representation and the posterior hippocampus supports fine-grained, local environmental representations.

    PubMed

    Evensmoen, Hallvard Røe; Lehn, Hanne; Xu, Jian; Witter, Menno P; Nadel, Lynn; Håberg, Asta K

    2013-11-01

    Representing an environment globally, in a coarse way, and locally, in a fine-grained way, are two fundamental aspects of how our brain interprets the world that surrounds us. The neural correlates of these representations have not been explicated in humans. In this study we used fMRI to investigate these correlates and to explore a possible functional segregation in the hippocampus and parietal cortex. We hypothesized that processing a coarse, global environmental representation engages anterior parts of these regions, whereas processing fine-grained, local environmental information engages posterior parts. Participants learned a virtual environment and then had to find their way during fMRI. After scanning, we assessed strategies used and representations stored. Activation in the hippocampal head (anterior) was related to the multiple distance and global direction judgments and to the use of a coarse, global environmental representation during navigation. Activation in the hippocampal tail (posterior) was related to both local and global direction judgments and to using strategies like number of turns. A structural shape analysis showed that the use of a coarse, global environmental representation was related to larger right hippocampal head volume and smaller right hippocampal tail volume. In the inferior parietal cortex, a similar functional segregation was observed, with global routes represented anteriorly and fine-grained route information such as number of turns represented posteriorly. In conclusion, moving from the anterior to the posterior hippocampus and inferior parietal cortex reflects a shift from processing coarse global environmental representations to processing fine-grained, local environmental representations.

  20. 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

  1. 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

  2. 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

  3. Using bivariate signal analysis to characterize the epileptic focus: The benefit of surrogates

    NASA Astrophysics Data System (ADS)

    Andrzejak, R. G.; Chicharro, D.; Lehnertz, K.; Mormann, F.

    2011-04-01

    The disease epilepsy is related to hypersynchronous activity of networks of neurons. While acute epileptic seizures are the most extreme manifestation of this hypersynchronous activity, an elevated level of interdependence of neuronal dynamics is thought to persist also during the seizure-free interval. In multichannel recordings from brain areas involved in the epileptic process, this interdependence can be reflected in an increased linear cross correlation but also in signal properties of higher order. Bivariate time series analysis comprises a variety of approaches, each with different degrees of sensitivity and specificity for interdependencies reflected in lower- or higher-order properties of pairs of simultaneously recorded signals. Here we investigate which approach is best suited to detect putatively elevated interdependence levels in signals recorded from brain areas involved in the epileptic process. For this purpose, we use the linear cross correlation that is sensitive to lower-order signatures of interdependence, a nonlinear interdependence measure that integrates both lower- and higher-order properties, and a surrogate-corrected nonlinear interdependence measure that aims to specifically characterize higher-order properties. We analyze intracranial electroencephalographic recordings of the seizure-free interval from 29 patients with an epileptic focus located in the medial temporal lobe. Our results show that all three approaches detect higher levels of interdependence for signals recorded from the brain hemisphere containing the epileptic focus as compared to signals recorded from the opposite hemisphere. For the linear cross correlation, however, these differences are not significant. For the nonlinear interdependence measure, results are significant but only of moderate accuracy with regard to the discriminative power for the focal and nonfocal hemispheres. The highest significance and accuracy is obtained for the surrogate-corrected nonlinear

  4. 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.

  5. 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…

  6. 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

  7. Neuroinflammation in the normal aging hippocampus.

    PubMed

    Barrientos, R M; Kitt, M M; Watkins, L R; Maier, S F

    2015-11-19

    A consequence of normal aging is a greater susceptibility to memory impairments following an immune challenge such as infection, surgery, or traumatic brain injury. The neuroinflammatory response, produced by these challenges results in increased and prolonged production of pro-inflammatory cytokines in the otherwise healthy aged brain. Here we discuss the mechanisms by which long-lasting elevations in pro-inflammatory cytokines in the hippocampus produce memory impairments. Sensitized microglia are a primary source of this exaggerated neuroinflammatory response and appear to be a hallmark of the normal aging brain. We review the current understanding of the causes and effects of normal aging-induced microglial sensitization, including dysregulations of the neuroendocrine system, potentiation of neuroinflammatory responses following an immune challenge, and the impairment of memories. We end with a discussion of therapeutic approaches to prevent these deleterious effects.

  8. Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats.

    PubMed

    Maren, Stephen

    2008-10-01

    Pavlovian fear conditioning has become an important model for investigating the neural substrates of learning and memory in rats, mice and humans. The hippocampus and amygdala are widely believed to be essential for fear conditioning to contexts and discrete cues, respectively. Indeed, this parsing of function within the fear circuit has been used to leverage fear conditioning as a behavioral assay of hippocampal and amygdala function, particularly in transgenic mouse models. Recent work, however, blurs the anatomical segregation of cue and context conditioning and challenges the necessity for the hippocampus and amygdala in fear learning. Moreover, nonassociative factors may influence the performance of fear responses under a variety of conditions. Caution must therefore be exercised when using fear conditioning as a behavioral assay for hippocampal- and amygdala-dependent learning.

  9. Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats.

    PubMed

    Maren, Stephen

    2008-10-01

    Pavlovian fear conditioning has become an important model for investigating the neural substrates of learning and memory in rats, mice and humans. The hippocampus and amygdala are widely believed to be essential for fear conditioning to contexts and discrete cues, respectively. Indeed, this parsing of function within the fear circuit has been used to leverage fear conditioning as a behavioral assay of hippocampal and amygdala function, particularly in transgenic mouse models. Recent work, however, blurs the anatomical segregation of cue and context conditioning and challenges the necessity for the hippocampus and amygdala in fear learning. Moreover, nonassociative factors may influence the performance of fear responses under a variety of conditions. Caution must therefore be exercised when using fear conditioning as a behavioral assay for hippocampal- and amygdala-dependent learning. PMID:18973583

  10. 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

  11. 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

  12. [Epilepsy from a metaphysical perspective: an interpretation of the biblical story of the epileptic boy and Raphael's Transfiguration].

    PubMed

    Janz, D

    1994-01-01

    Raphael's last painting reveals, in the upper half of the picture, Christ's transfiguration on Mount Tabor and, in the lower half, the young boy's epileptic seizure at the foot of the mountain in the presence of the other disciples. Raphael depicts both events, which are told in succession in the Gospels, as if they took place at the same time. By synchronizing both scenes, Raphael demonstrated a significant correspondence between Christ and the epileptic boy which reveals the epileptic seizure as a symbolic representation of a transcendental event. This metaphysical aspect of epilepsy depicted by Raphael can also be found in the corresponding biblical passages. In the Gospels, the metamorphosis caused by the epileptic seizure is used as a simile for Christ's transfiguration through suffering, death and resurrection.

  13. 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.

  14. How the hippocampus preserves order: the role of prediction and context

    PubMed Central

    Davachi, Lila; DuBrow, Sarah

    2015-01-01

    Remembering the sequence of events is critical for deriving meaning from our experiences and guiding behavior. Prior investigations into the function of the human hippocampus have focused on its more general role in associative binding, but recent work has focused on understanding its specific role in encoding and preserving the temporal order of experiences. In this review, we summarize recent work in humans examining hippocampal contributions to sequence learning. We distinguish the learning of sequential relationships through repetition from the rapid, episodic acquisition of sequential associations. Together, this research begins to clarify the link between hippocampal representations and the preservation of the order of events. PMID:25600586

  15. 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

  16. 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.

  17. 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

  18. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

    PubMed Central

    2012-01-01

    Abstact Background Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. Methods In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Results Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Conclusions Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management. PMID:22364254

  19. ICA extracts epileptic sources from fMRI in EEG-negative patients: a retrospective validation study.

    PubMed

    Hunyadi, Borbála; Tousseyn, Simon; Mijović, Bogdan; Dupont, Patrick; Van Huffel, Sabine; Van Paesschen, Wim; De Vos, Maarten

    2013-01-01

    Simultaneous EEG-fMRI has proven to be useful in localizing interictal epileptic activity. However, the applicability of traditional GLM-based analysis is limited as interictal spikes are often not seen on the EEG inside the scanner. Therefore, we aim at extracting epileptic activity purely from the fMRI time series using independent component analysis (ICA). To our knowledge, we show for the first time that ICA can find sources related to epileptic activity in patients where no interictal spikes were recorded in the EEG. The epileptic components were identified retrospectively based on the known localization of the ictal onset zone (IOZ). We demonstrate that the selected components truly correspond to epileptic activity, as sources extracted from patients resemble significantly better the IOZ than sources found in healthy controls. Furthermore, we show that the epileptic components in patients with and without spikes recorded inside the scanner resemble the IOZ in the same degree. We conclude that ICA of fMRI has the potential to extend the applicability of EEG-fMRI for presurgical evaluation in epilepsy.

  20. GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction.

    PubMed

    Lesca, Gaetan; Rudolf, Gabrielle; Bruneau, Nadine; Lozovaya, Natalia; Labalme, Audrey; Boutry-Kryza, Nadia; Salmi, Manal; Tsintsadze, Timur; Addis, Laura; Motte, Jacques; Wright, Sukhvir; Tsintsadze, Vera; Michel, Anne; Doummar, Diane; Lascelles, Karine; Strug, Lisa; Waters, Patrick; de Bellescize, Julitta; Vrielynck, Pascal; de Saint Martin, Anne; Ville, Dorothee; Ryvlin, Philippe; Arzimanoglou, Alexis; Hirsch, Edouard; Vincent, Angela; Pal, Deb; Burnashev, Nail; Sanlaville, Damien; Szepetowski, Pierre

    2013-09-01

    Epileptic encephalopathies are severe brain disorders with the epileptic component contributing to the worsening of cognitive and behavioral manifestations. Acquired epileptic aphasia (Landau-Kleffner syndrome, LKS) and continuous spike and waves during slow-wave sleep syndrome (CSWSS) represent rare and closely related childhood focal epileptic encephalopathies of unknown etiology. They show electroclinical overlap with rolandic epilepsy (the most frequent childhood focal epilepsy) and can be viewed as different clinical expressions of a single pathological entity situated at the crossroads of epileptic, speech, language, cognitive and behavioral disorders. Here we demonstrate that about 20% of cases of LKS, CSWSS and electroclinically atypical rolandic epilepsy often associated with speech impairment can have a genetic origin sustained by de novo or inherited mutations in the GRIN2A gene (encoding the N-methyl-D-aspartate (NMDA) glutamate receptor α2 subunit, GluN2A). The identification of GRIN2A as a major gene for these epileptic encephalopathies provides crucial insights into the underlying pathophysiology.

  1. 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

  2. Ictal hallucination and hemispheric specialization: findings from 217 cases with a unilateral epileptic focus.

    PubMed

    Guimond, Anik; Braun, Claude M J; Daigneault, Rafael

    2009-10-01

    Epileptic populations are generally considered inappropriate to investigate hemispheric specialization. However, (1) because hallucination occurs in the early stage of the ictus during which activation is observed in and around the focus, the former could be a direct result of the latter (hypothesis 1), and (2) the type of psychological content of ictal hallucination could depend on which hemisphere is ictally activated (hypothesis 2). It was predicted that, on the basis of quantitative analysis of previously published singles case reports, unilateral ictal hallucinations should occur in the visual field, ear or hemibody contralateral to the side of the ictal focus (test of hypothesis 1). It was also predicted that verbal ictal auditory hallucinations should result more often from left hemisphere foci, and non-verbal auditory ictal hallucinations from right hemisphere foci (test of hypothesis 2). Previously published cases (N=217) of ictal hallucination from a unilateral epileptic focus were reviewed and analyzed with multivariate statistics. Both predictions were strongly supported.

  3. 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

  4. The influence of hubs in the structure of a neuronal network during an epileptic seizure

    NASA Astrophysics Data System (ADS)

    Rodrigues, Abner Cardoso; Cerdeira, Hilda A.; Machado, Birajara Soares

    2016-02-01

    In this work, we propose changes in the structure of a neuronal network with the intention to provoke strong synchronization to simulate episodes of epileptic seizure. Starting with a network of Izhikevich neurons we slowly increase the number of connections in selected nodes in a controlled way, to produce (or not) hubs. We study how these structures alter the synchronization on the spike firings interval, on individual neurons as well as on mean values, as a function of the concentration of connections for random and non-random (hubs) distribution. We also analyze how the post-ictal signal varies for the different distributions. We conclude that a network with hubs is more appropriate to represent an epileptic state.

  5. 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.

  6. 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

  7. Real-time Detection of Precursors to Epileptic Seizures: Non-Linear Analysis of System Dynamics.

    PubMed

    Nesaei, Sahar; Sharafat, Ahmad R

    2014-04-01

    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.

  8. 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

  9. A comprehensive oral and dental management of an epileptic and intellectually deteriorated adolescent

    PubMed Central

    Joshi, Sourabh Ramesh; Pendyala, Gowri Swaminatham; Saraf, Veena; Choudhari, Shantanu; Mopagar, Viddyasagar

    2013-01-01

    Epilepsy along with intellectual deterioration and other neurological disorders can have social, physical, and psychological consequences, especially, when they begin in childhood. Moreover, the seizure episode along with mental deterioration may compromise the oral and dental care resulting in numerous decayed teeth. This report presents the case history of an adolescent with poor oral hygiene and numerous decayed teeth. This report also presents the comprehensive endodontic, surgical, and prosthodontic management of epileptic mentally challenged patient in the dental office. Epilepsy along with intellectual deterioration and other neurological disorders can have social, physical, and psychological consequences, especially, when they begin in childhood. Moreover, the seizure episode along with mental deterioration may compromise the oral and dental care resulting in numerous decayed teeth. This report presents the case history of an adolescent with poor oral hygiene and numerous decayed teeth. This report also presents the comprehensive endodontic, surgical, and prosthodontic management of epileptic mentally challenged patient in the dental office. PMID:24130597

  10. Localization and cure of epileptic foci with the use of MEG measurements.

    PubMed

    Anninos, P A; Tsagas, N

    1989-06-01

    Systematic studies with pathological subjects with focal and general epilepsies using magnetoencephalographic (MEG) measurements showed significant brain activities even if they are not present in the electroencephalogram EEG. Using a mapping technique characterized by an isospectral amplitude (ISO-SA) of the scalp distribution of specified spectral components or frequency bands of the MEG power spectrum we were able to localize the epileptic foci. This localization of epileptic foci gives us information on the emitted magnetic field intensity and frequency for each focal point on the map of the patient. Using this information we can cure the patient by adjusting an electronic device which can emit back to the specific scalp point a magnetic field of the same intensity and frequency as the one which-is emitted from it. The principle of this technique is based on the physical phenomenon of Young's double-slit experiment by which under certain condition light plus light gives darkness.

  11. 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

  12. Topiramate-induced paresthesia is more frequently reported by migraine than epileptic patients.

    PubMed

    Sedighi, Behnaz; Shafiei, Kaveh; Azizpour, Iman

    2016-04-01

    Topiramate is an approved and effective drug in migraine prophylaxis. Paresthesia is the most commonly reported side effect. The primary objective of this study was to compare the frequency of topiramate-induced paresthesia in migraine headache to epileptic patients. Patients with migraine without aura and epilepsy were enrolled in this observational study. All cases were interviewed by telephone about their history of paresthesia. Confounding factors were controlled through logistic regression. The odds ratio of developing topiramate-induced paresthesia in migraine compared to epilepsy patients was 3.4. Three factors were independent contributors to developing topiramate-induced paresthesia: female sex (odds ratio 2.1), topiramate dosage (odds ratio 0.3) and duration of therapy. Our findings indicate an independent association between migraine and development of paresthesia. Migraineurs were more likely than epileptic patients to report paresthesia as topiramate adverse effects. Female sex, treatment duration and topiramate dosage contribute significantly to subsequent development of paresthesia.

  13. 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

  14. Circulating hormones and pituitary responsiveness in young epileptic men receiving long-term antiepileptic medication.

    PubMed

    Macphee, G J; Larkin, J G; Butler, E; Beastall, G H; Brodie, M J

    1988-01-01

    Impairment of libido and sexual potency are commonly reported by male epileptic patients. This may be partly a consequence of medication. Circulating hormones were measured in 53 postpubertal male epileptic patients less than 45 years of age and in an age-matched control group (n = 40), consisting of 14 untreated epileptic patients and 26 unmedicated healthy subjects. A subgroup also underwent a combined gonadotrophin- and thyrotrophin-releasing hormone (LH-RH/TRH) pituitary stimulation test. Untreated patients did not differ from healthy subjects for any parameter, and their data were combined for comparison with the treated epileptic patients. Total testosterone (T), androstenedione, and basal follicle-stimulating hormone concentrations were similar in all patient groups. Patients receiving more than one drug had higher sex hormone binding globulin (SHBG) (p less than 0.01) and lower free T and dehydroepiandrosterone sulphate (DHAS) levels (both p less than 0.001) than controls. Carbamazepine (CBZ) monotherapy also reduced free T (p less than 0.05) and DHAS (p less than 0.001) and increased basal prolactin (p less than 0.01). In these two groups of patients, basal luteinising hormone (LH) was elevated (p less than 0.01), presumably as a pituitary response to increased T catabolism. There was a negative correlation between free T and circulating CBZ (r = -0.54, p less than 0.05) in the monotherapy patients. Phenytoin (PHT) was associated with a rise in SHBG (p less than 0.01) and a fall in DHAS (p less than 0.001). Basal LH was also elevated, but this just failed to reach statistical significance (p less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Burn injury in epileptic patients: an experience in a tertiary institute

    PubMed Central

    Akhtar, M.S.; Ahmad, I.; Khan, A.H.; Fahud Khurram, M.; Haq, A.

    2014-01-01

    Summary 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

  16. [An analysis of criminal liability in a criminal case involving an epileptic].

    PubMed

    Liu, H

    1989-12-01

    This paper presents the case of an epileptic patient who killed his wife during the intermittent period of epilepsy: three different units were asked to give the forensic psychiatric appraisement which came to three different conclusions, namely, the patient should be entitled to no criminal responsibility, partial criminal responsibility, and full criminal responsibility with respect to these three conclusions, the authors make a detailed discussion and give their own opinions.

  17. Occurrence of bilaterally independent epileptic spasms after a corpus callosotomy in West syndrome.

    PubMed

    Kobayashi, Katsuhiro; Endoh, Fumika; Toda, Yoshihiro; Oka, Makio; Baba, Hiroshi; Ohtsuka, Yoko; Yoshinaga, Harumi

    2016-01-01

    We report a patient with intractable West syndrome whose epileptic spasms (ESs) were initially bilaterally synchronous, as is typical; after a complete corpus callosotomy, however, bilaterally independent ESs originated in either hemisphere. Activity of probable cortical origin associated with ESs was detected by observing ictal gamma oscillations. Brain MRI revealed no structural abnormality before surgery. This case suggests that ESs with a hemispheric origin may appear generalized because of synchronizing effects in the corpus callosum in some patients.

  18. 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.

  19. 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.

  20. Alterations of endocannabinoids in cerebrospinal fluid of dogs with epileptic seizure disorder

    PubMed Central

    2013-01-01

    Background Epilepsy is one of the most common chronic neurological disorders in dogs characterized by recurrent seizures. The endocannabinoid (EC) system plays a central role in suppressing pathologic neuronal excitability and in controlling the spread of activity in an epileptic network. Endocannabinoids are released on demand and their dysregulation has been described in several pathological conditions. Recurrent seizures may lead to an adverse reorganization of the EC system and impairment of its protective effect. In the current study, we tested the hypothesis that cerebrospinal fluid (CSF) concentrations of the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2AG) are altered in epileptic dogs. Concentrations of AEA and total AG (sum of 2AG and 1AG) were measured in 40 dogs with idiopathic epilepsy and in 16 unaffected, healthy control dogs using liquid chromatography combined with tandem mass spectrometry. Results AEA and total AG were measured at 4.94 (3.18 – 9.17) pM and 1.43 (0.90 – 1.92) nM in epileptic dogs and at 3.19 (2.04 – 4.28) pM and 1.76 (1.08 – 2.69) nM in the control group, respectively (median, 25 – 75% percentiles in brackets). The AEA difference between epileptic and healthy dogs was statistically significant (p < 0.05). Values correlated with seizure severity and duration of seizure activity. Dogs with cluster seizures and/or status epilepticus and with seizure activity for more than six months displayed the highest EC concentrations. Conclusion In conclusion, we present the first endocannabinoid measurements in canine CSF and confirm the hypothesis that the EC system is altered in canine idiopathic epilepsy. PMID:24370333

  1. 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

  2. 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.

  3. Respiratory Viral Infection in Neonatal Piglets Causes Marked Microglia Activation in the Hippocampus and Deficits in Spatial Learning

    PubMed Central

    Elmore, Monica R. P.; Burton, Michael D.; Conrad, Matthew S.; Rytych, Jennifer L.; Van Alstine, William G.

    2014-01-01

    Environmental insults during sensitive periods can affect hippocampal development and function, but little is known about peripheral infection, especially in humans and other animals whose brain is gyrencephalic and experiences major perinatal growth. Using a piglet model, the present study showed that inoculation on postnatal day 7 with the porcine reproductive and respiratory syndrome virus (PRRSV) caused microglial activation within the hippocampus with 82% and 43% of isolated microglia being MHC II+ 13 and 20 d after inoculation, respectively. In control piglets, <5% of microglia isolated from the hippocampus were MHC II+. PRRSV piglets were febrile (p < 0.0001), anorectic (p < 0.0001), and weighed less at the end of the study (p = 0.002) compared with control piglets. Increased inflammatory gene expression (e.g., IL-1β, IL-6, TNF-α, and IFN-γ) was seen across multiple brain regions, including the hippocampus, whereas reductions in CD200, NGF, and MBP were evident. In a test of spatial learning, PRRSV piglets took longer to acquire the task, had a longer latency to choice, and had a higher total distance moved. Overall, these data demonstrate that viral respiratory infection is associated with a marked increase in activated microglia in the hippocampus, neuroinflammation, and impaired performance in a spatial cognitive task. As respiratory infections are common in human neonates and infants, approaches to regulate microglial cell activity are likely to be important. PMID:24501353

  4. 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

  5. Hippocampus ghrelin signaling mediates appetite through lateral hypothalamic orexin pathways.

    PubMed

    Hsu, Ted M; Hahn, Joel D; Konanur, Vaibhav R; Noble, Emily E; Suarez, Andrea N; Thai, Jessica; Nakamoto, Emily M; Kanoski, Scott E

    2015-12-15

    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.

  6. 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

  7. 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

  8. Hippocampus and striatum: dynamics and interaction during acquisition and sleep-related motor sequence memory consolidation.

    PubMed

    Albouy, Geneviève; King, Bradley R; Maquet, Pierre; Doyon, Julien

    2013-11-01

    While several models of memory consolidation have previously associated hippocampal activity with declarative memory, there is now increasing evidence that the hippocampus also plays a crucial role in procedural memory. Here, we review recent human functional neuroimaging studies demonstrating that the hippocampus is involved in the acquisition and sleep-related consolidation of procedural memories, and motor sequence-based skills in particular. More specifically, we present evidence that hippocampal activity and its functional interactions with other brain structures, particularly competition with the striatum, contribute to initial learning of sequential motor behavior. Interestingly, these early cerebral representations in the hippocampus and striatum, which may interact through the prefrontal cortex, can even predict subsequent sleep-related memory consolidation processes. We propose that sleep can reorganize the activity within, as well as the functional interactions between, these structures, ultimately favoring overnight performance enhancement. Finally, we conclude by offering insights into the respective roles of these structures in procedural memory consolidation processes. We argue that, in the context of motor sequence memory consolidation, the hippocampal system triggers subsequent sleep-dependent performance enhancement whereas the striatal system is involved in the maintenance of the motor behavior over time.

  9. The relationships of dog hippocampus to sex and paw preference.

    PubMed

    Aydinlioglu, Atif; Arslan, Kadir; Cengiz, Nurettin; Ragbetli, Murat; Erdogan, Ender

    2006-01-01

    Previous studies have described paw preference and asymmetry in dog brains. Electrical activity of the dorsal hippocampus also indicated the existence of hippocampal asymmetry in dogs. In the present study, the possible paw and sex-related asymmetries and right-left differences in dog hippocampus were investigated. The hippocampus was dissected and weighed. Each hippocampus was cut into slices by the slicing apparatus placed horizontally on the tissues. The volumetric measurements were performed using the formula modified from the Cavalieri principle. The present study indicated the significant sex and paw differences and no right-left asymmetry in dog hippocampi. The morphological asymmetries in normal subjects might be related to functional hippocampal asymmetries in memory or in cognitive skills.

  10. 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

  11. 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

  12. 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

  13. The Classical Pathways of Occipital Lobe Epileptic Propagation Revised in the Light of White Matter Dissection.

    PubMed

    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.

  14. Brain Graph Topology Changes Associated with Anti-Epileptic Drug Use.

    PubMed

    Haneef, Zulfi; Levin, Harvey S; Chiang, Sharon

    2015-06-01

    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.

  15. 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

  16. GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy.

    PubMed

    Papandreou, Apostolos; McTague, Amy; Trump, Natalie; Ambegaonkar, Gautam; Ngoh, Adeline; Meyer, Esther; Scott, Richard H; Kurian, Manju A

    2016-04-01

    The gamma-aminobutyric acid type A receptor β3 gene (GABRB3) encodes the β3-subunit of the gamma-aminobutyric acid type A (GABAA ) receptor, which mediates inhibitory signalling within the central nervous system. Recently, GABRB3 mutations have been identified in a few patients with infantile spasms and Lennox-Gastaut syndrome. We report the clinical and electrographic features of a novel case of GABRB3-related early-onset epileptic encephalopathy. Our patient presented with neonatal hypotonia and feeding difficulties, then developed pharmacoresistant epileptic encephalopathy, characterized by multiple seizure types from 3 months of age. Electroencephalography demonstrated ictal generalized and interictal multifocal epileptiform abnormalities. Using a SureSelectXT custom multiple gene panel covering 48 early infantile epileptic encephalopathy/developmental delay genes, a novel de novo GABRB3 heterozygous missense mutation, c.860C>T (p.Thr287Ile), was identified and confirmed on Sanger sequencing. GABRB3 is an emerging cause of early-onset epilepsy. Novel genetic technologies, such as whole-exome/genome sequencing and multiple gene panels, will undoubtedly identify further cases, allowing more detailed electroclinical delineation of the GABRB3-related genotypic and phenotypic spectra.

  17. 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.

  18. Usefulness of MEG magnetometer for spike detection in patients with mesial temporal epileptic focus.

    PubMed

    Enatsu, R; Mikuni, N; Usui, K; Matsubayashi, J; Taki, J; Begum, T; Matsumoto, R; Ikeda, A; Nagamine, T; Fukuyama, H; Hashimoto, N

    2008-07-15

    The present study investigated the sensitivity of magnetoencephalography (MEG) for spikes depending on sensor type in patients with mesial temporal epileptic focus. We recorded MEG in 6 patients with mesial temporal epileptic focus using two sensor types (magnetometer and gradiometer) simultaneously. The number of spikes detected and the corresponding equivalent current dipole (ECD) parameters (distance from the coordinated head center (radius), and dipole moment) were evaluated with respect to sensor type. Among 426 MEG 'consensus spikes' determined by 3 reviewers, 378 spikes satisfied the predetermined criteria for source localization. Comparing ECD parameters, spikes detected by magnetometer alone displayed a smaller radius and larger dipole moment than those detected by gradiometer alone. Spikes estimated in the mesial temporal area were more frequently detected by magnetometer alone (38.5%) than by gradiometer alone (11.5%), whereas spikes in the lateral temporal area were detected less by magnetometer alone (3.7%) than by gradiometer alone (53.9%). The present results suggest that a magnetometer is advantageous for spike detection in patients with mesial temporal epileptic focus. This also implies the higher sensitivity of magnetometer for deep sources.

  19. Epileptic Pattern Recognition and Discovery of the Local Field Potential in Amygdala Kindling Process.

    PubMed

    Wang, Yu-Lin; Chen, Yin-Lin; Su, Alvin Wen-Yu; Shaw, Fu-Zen; Liang, Sheng-Fu

    2016-03-01

    Epileptogenesis, which occurs in an epileptic brain, is an important focus for epilepsy. The spectral analysis has been popularly applied to study the electrophysiological activities. However, the resolution is dominated by the window function of the algorithm used and the sample size. In this report, a temporal waveform analysis method is proposed to investigate the relationship of electrophysiological discharges and motor outcomes with a kindling process. Wistar rats were subjected to electrical amygdala kindling to induce temporal lobe epilepsy. During the kindling process, different morphologies of afterdischarges (ADs) were found and a recognition method, using template matching techniques combined with morphological comparators, was developed to automatically detect the epileptic patterns. The recognition results were compared to manually labeled results, and 79%-91% sensitivity was found. In addition, the initial ADs (the first 10 s) of different seizure stages were specifically utilized for recognition, and an average of 85% sensitivity was achieved. Our study provides an alternative viewpoint away from frequency analysis and time-frequency analysis to investigate epileptogenesis in an epileptic brain. The recognition method can be utilized as a preliminary inspection tool to identify remarkable changes in a patient's electrophysiological activities for clinical use. Moreover, we demonstrate the feasibility of predicting behavioral seizure stages from the early epileptiform discharges.

  20. 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

  1. Hippocampus, delay discounting, and vicarious trial-and-error.

    PubMed

    Bett, David; Murdoch, Lauren H; Wood, Emma R; Dudchenko, Paul A

    2015-05-01

    In decision-making, an immediate reward is usually preferred to a delayed reward, even if the latter is larger. We tested whether the hippocampus is necessary for this form of temporal discounting, and for vicarious trial-and-error at the decision point. Rats were trained on a recently developed, adjustable delay-discounting task (Papale et al. (2012) Cogn Affect Behav Neurosci 12:513-526), which featured a choice between a small, nearly immediate reward, and a larger, delayed reward. Rats then received either hippocampus or sham lesions. Animals with hippocampus lesions adjusted the delay for the larger reward to a level similar to that of sham-lesioned animals, suggesting a similar valuation capacity. However, the hippocampus lesion group spent significantly longer investigating the small and large rewards in the first part of the sessions, and were less sensitive to changes in the amount of reward in the large reward maze arm. Both sham- and hippocampus-lesioned rats showed a greater amount of vicarious trial-and-error on trials in which the delay was adjusted. In a nonadjusting version of the delay discounting task, animals with hippocampus lesions showed more variability in their preference for a larger reward that was delayed by 10 s compared with sham-lesioned animals. To verify the lesion behaviorally, rat were subsequently trained on a water maze task, and rats with hippocampus lesions were significantly impaired compared with sham-lesioned animals. The findings on the delay discounting tasks suggest that damage to the hippocampus may impair the detection of reward magnitude.

  2. 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.

  3. 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

  4. Estrogen Receptors, the Hippocampus, and Memory

    PubMed Central

    Bean, Linda A.; Ianov, Lara; Foster, Thomas C.

    2015-01-01

    Estradiol effects on memory depend on hormone levels and the interaction of different estrogen receptors within neural circuits. Estradiol induces gene transcription and rapid membrane signaling mediated by estrogen receptor-alpha (ERα), estrogen receptor-beta (ERβ), and a recently characterized G-protein coupled estrogen receptor, each with distinct distributions and ability to influence estradiol-dependent signaling. Investigations using receptor specific agonists suggest that all three receptors rapidly activate kinase-signaling and have complex dose-dependent influences on memory. Research employing receptor knockout mice demonstrate that ERα maintains transcription and memory as estradiol levels decline. This work indicates a regulatory role of ERβ in transcription and cognition, which depends on estradiol levels and the function of ERα. The regulatory role of ERβ is due in part to ERβ acting as a negative regulator of ERα-mediated transcription. Vector-mediated expression of estrogen receptors in the hippocampus provides an innovative research approach and suggests that memory depends on the relative expression of ERα and ERβ interacting with estradiol levels. Notably, the ability of estradiol to improve cognition declines with advanced age along with decreased expression of estrogen receptors. Thus, it will be important for future research to determine the mechanisms that regulate estrogen receptor expression during aging. PMID:24510074

  5. 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

  6. Encoding and retrieval along the long axis of the hippocampus and their relationships with dorsal attention and default mode networks: The HERNET model.

    PubMed

    Kim, Hongkeun

    2015-04-01

    The encoding of sensory input is intertwined with external attention, whereas retrieval is intrinsically related to internal attention. This study proposes a model in which the encoding of sensory input involves mainly the anterior hippocampus and the external attention network, whereas retrieval, the posterior hippocampus and the internal attention network. This model is referred to as the HERNET (hippocampal encoding/retrieval and network) model. Functional neuroimaging studies have identified two intrinsic large-scale networks closely associated with external and internal attention, respectively. The dorsal attention network activates during any externally oriented mental activity, whereas the default mode network shows increased activity during internally oriented mental activity. Therefore, the HERNET model may predict the activation of the anterior hippocampus and the dorsal attention network during the encoding and activation of the posterior hippocampus and the default mode network during retrieval. To test this prediction, this study provides a meta-analysis of three memory-imaging paradigms: subsequent memory, laboratory-based recollection, and autobiographical memory retrieval. The meta-analysis included 167 individual studies and 2,856 participants. The results provide support for the HERNET model and suggest that the anterior-posterior gradient of encoding and retrieval includes amygdala regions. More broadly, humans continuously oscillate between external and internal attention and thus between encoding and retrieval processes. These oscillations may involve repetitive and spontaneous activity switching between the anterior hippocampus/dorsal attention network and the posterior hippocampus/default mode network.

  7. Relating Hippocampus to Relational Memory Processing across Domains and Delays

    PubMed Central

    Monti, Jim M.; Cooke, Gillian E.; Watson, Patrick D.; Voss, Michelle W.; Kramer, Arthur F.; Cohen, Neal J.

    2015-01-01

    The hippocampus has been implicated in a diverse set of cognitive domains and paradigms, including cognitive mapping, long-term memory, and relational memory, at long or short study–test intervals. Despite the diversity of these areas, their association with the hippocampus may rely on an underlying commonality of relational memory processing shared among them. Most studies assess hippocampal memory within just one of these domains, making it difficult to know whether these paradigms all assess a similar underlying cognitive construct tied to the hippocampus. Here we directly tested the commonality among disparate tasks linked to the hippocampus by using PCA on performance from a battery of 12 cognitive tasks that included two traditional, long-delay neuropsychological tests of memory and two laboratory tests of relational memory (one of spatial and one of visual object associations) that imposed only short delays between study and test. Also included were different tests of memory, executive function, and processing speed. Structural MRI scans from a subset of participants were used to quantify the volume of the hippocampus and other subcortical regions. Results revealed that the 12 tasks clustered into four components; critically, the two neuropsychological tasks of long-term verbal memory and the two laboratory tests of relational memory loaded onto one component. Moreover, bilateral hippocampal volume was strongly tied to performance on this component. Taken together, these data emphasize the important contribution the hippocampus makes to relational memory processing across a broad range of tasks that span multiple domains. PMID:25203273

  8. Effects of antiepileptic drugs on the serum folate and vitamin B12 in various epileptic patients

    PubMed Central

    Huang, Hong-Li; Zhou