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Sample records for epileptic human hippocampus

  1. The functional organization of human epileptic hippocampus.

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-08-20

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

  5. Spread of epileptic activity in human brain

    NASA Astrophysics Data System (ADS)

    Milton, John

    1997-03-01

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

  6. Evolving networks in the human epileptic brain

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

  7. Hippocampus and epilepsy: Findings from human tissues.

    PubMed

    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

  8. Hippocampus and epilepsy: findings from human tissues

    PubMed Central

    Huberfeld, Gilles; Blauwblomme, Thomas; Miles, Richard

    2015-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Concepts of Connectivity and Human Epileptic Activity

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  13. Mnemonic convergence in the human hippocampus.

    PubMed

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

    2016-01-01

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

  14. Mnemonic convergence in the human hippocampus

    PubMed 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

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

    NASA Astrophysics Data System (ADS)

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

    2008-09-01

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

  16. Gene expression profiling in developing human hippocampus.

    PubMed

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

    2002-10-15

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

  17. Traveling Theta Waves in the Human Hippocampus.

    PubMed

    Zhang, Honghui; Jacobs, Joshua

    2015-09-01

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

  18. Attention Stabilizes Representations in the Human Hippocampus.

    PubMed

    Aly, Mariam; Turk-Browne, Nicholas B

    2016-02-01

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

  19. Proteome map of the human hippocampus.

    PubMed

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

    1999-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed 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

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

    NASA Astrophysics Data System (ADS)

    Lehnertz, Klaus

    2006-03-01

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

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

    PubMed

    Tankus, Ariel

    2016-05-01

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

  4. Musical Training Induces Functional Plasticity in Human Hippocampus

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Soltanian-Zadeh, Hamid; Siadat, Mohammad-Reza

    1999-05-01

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

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

    PubMed

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Li, Dingzhou

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

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

    SciTech Connect

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

    1982-10-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2005-01-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    2010-03-23

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

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

    PubMed

    Szabó, C Ákos; Salinas, Felipe S

    2016-08-01

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

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

    PubMed

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

    2016-06-10

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    PubMed Central

    Villa, Chiara; Combi, Romina

    2016-01-01

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

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

    PubMed

    Villa, Chiara; Combi, Romina

    2016-01-01

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

  1. Dopamine regulates stimulus generalization in the human hippocampus

    PubMed Central

    Kahnt, Thorsten; Tobler, Philippe N

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Hobbs, Jonathan Paul

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2002-10-01

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

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

    PubMed

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

    2002-11-12

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

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

    PubMed Central

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

    2002-01-01

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

  8. Domoic acid epileptic disease.

    PubMed

    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

  9. 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

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

    PubMed

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

    1996-06-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2009-02-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2005-10-01

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

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

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2002-09-01

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

  20. 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…

  1. 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

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

    NASA Astrophysics Data System (ADS)

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

    1995-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2004-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-01-01

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

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

    PubMed

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

    1992-09-01

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

  11. Antidepressants increase neural progenitor cells in the human hippocampus

    PubMed Central

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

    2009-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Neiman, Alexander

    2000-03-01

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

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

    PubMed

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

    1982-08-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2004-01-01

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

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

    PubMed

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

    2012-10-16

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  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. Electroencephalographic features of familial spontaneous epileptic cats.

    PubMed

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

    2014-08-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-05-01

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

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

    PubMed Central

    Clark, Robert E.; Squire, Larry R.

    2013-01-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Whittington, M A; Jefferys, J G

    1994-01-01

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

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

    PubMed

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

    2016-08-01

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

  16. Wavelet analysis of epileptic spikes

    NASA Astrophysics Data System (ADS)

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

    2003-05-01

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

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

    PubMed

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

    2008-07-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    1998-01-01

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

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

    SciTech Connect

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

    1995-10-10

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

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

    PubMed

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

    2016-01-01

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

  2. Analysis of epileptic seizures with complex network.

    PubMed

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

    2014-01-01

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

  3. [Unusual dreams in epileptics].

    PubMed

    Boldyrev, A I

    1984-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2009-01-01

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

  9. Treatment of epileptic encephalopathies.

    PubMed

    McTague, Amy; Cross, J Helen

    2013-03-01

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

  10. Human hippocampal theta activity during virtual navigation.

    PubMed

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

    2005-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2015-01-01

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

  13. The rat brain hippocampus proteome.

    PubMed

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

    2005-05-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2005-05-15

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

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

    PubMed

    Ito, Rutsuko; Lee, Andy C H

    2016-10-15

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

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

    PubMed

    Goldsmith, S K; Joyce, J N

    1994-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  19. De novo mutations in epileptic encephalopathies.

    PubMed

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

    2013-09-12

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

  20. [Genes Responsible for Epileptic Syndromes].

    PubMed

    Kato, Mitsuhiro

    2016-02-01

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

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

    PubMed

    Regesta, G; Tanganelli, P

    2000-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2007-02-01

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

  7. Epileptic activity recognition in EEG recording

    NASA Astrophysics Data System (ADS)

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

    1999-12-01

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

  8. Imaging DC MEG Fields Associated with Epileptic Onset

    NASA Astrophysics Data System (ADS)

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

    2004-10-01

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

  9. Global Interactions Analysis of Epileptic ECoG Data

    NASA Astrophysics Data System (ADS)

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

    2007-05-01

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

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

    PubMed Central

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

    2014-01-01

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

  11. Hsp60 response in experimental and human temporal lobe epilepsy

    PubMed Central

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

    2015-01-01

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

  12. Fractal Dimension in Epileptic EEG Signal Analysis

    NASA Astrophysics Data System (ADS)

    Uthayakumar, R.

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

  13. How Sleep Activates Epileptic Networks?

    PubMed Central

    Halász, Peter

    2013-01-01

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

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

    PubMed

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

    2016-02-01

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

  15. Epileptic Seizure Forewarning by Nonlinear Techniques

    SciTech Connect

    Hively, L.M.

    2002-04-19

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

  16. Nonlinear analysis of EEG for epileptic seizures

    SciTech Connect

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

    1995-04-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2011-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2009-10-01

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

  1. [Drivers license qualification for epileptics].

    PubMed

    Egli, M; Hartmann, H; Hess, R

    1977-03-26

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-05-15

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

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

    PubMed

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

    2016-02-01

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

  5. The bumps on the hippocampus

    NASA Astrophysics Data System (ADS)

    Gao, Yi; Ver Hoef, Lawrence

    2016-03-01

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

  6. The hippocampus: a special place for time.

    PubMed

    Ranganath, Charan; Hsieh, Liang-Tien

    2016-04-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. Neurotransmission in the hippocampus

    SciTech Connect

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

    1988-01-01

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

  9. Metabolic Causes of Epileptic Encephalopathy

    PubMed Central

    Pearl, Phillip L.

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-07-01

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

  12. Post-epileptic headache and migraine.

    PubMed Central

    Schon, F; Blau, J N

    1987-01-01

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

  13. Current understanding and neurobiology of epileptic encephalopathies.

    PubMed

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

    2016-08-01

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

  14. Ambroxol-induced focal epileptic seizure.

    PubMed

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

    2014-01-01

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

  15. Newer anti-epileptic drugs.

    PubMed

    Aneja, S; Newton, R W

    1996-01-01

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

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

    PubMed

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

    2009-06-01

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

  17. Clinical review of genetic epileptic encephalopathies

    PubMed Central

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

    2012-01-01

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

  18. Chewing Maintains Hippocampus-Dependent Cognitive Function

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  20. Epileptic encephalopathies: new genes and new pathways.

    PubMed

    Nieh, Sahar Esmaeeli; Sherr, Elliott H

    2014-10-01

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

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

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2011-10-01

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

  3. Music and its association with epileptic disorders.

    PubMed

    Maguire, Melissa

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  5. Cell Signaling Underlying Epileptic Behavior

    PubMed Central

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

    2011-01-01

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

  6. 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…

  7. 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…

  8. Predicting Epileptic Seizures in Advance

    PubMed Central

    Moghim, Negin; Corne, David W.

    2014-01-01

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

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

    PubMed 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

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

    PubMed

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

    2015-09-01

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

  11. Pediatric Epileptic Encephalopathies: Pathophysiology and Animal Models.

    PubMed

    Shao, Li-Rong; Stafstrom, Carl E

    2016-05-01

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

  12. Sleep in epileptic beagles and antiepileptics.

    PubMed

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

    1986-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Hofmann, Markus J.; Kuchinke, Lars

    2015-06-01

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

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

    NASA Astrophysics Data System (ADS)

    Persinger, M. A.; Psych, C.

    1995-12-01

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

  15. Psychogenic non-epileptic seizures (PNES).

    PubMed

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

    2016-01-01

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

  16. [Psychodynamic aspects of the epileptic experience].

    PubMed

    Mazza, S; Azzoni, A

    1989-01-01

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

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

    PubMed

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

    1994-12-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. [Civil and criminal responsibility of epileptics].

    PubMed

    Villanueva, F

    1997-03-01

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

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

    NASA Astrophysics Data System (ADS)

    Trost, Wiebke; Frühholz, Sascha

    2015-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-09-01

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

  5. 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

  6. 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

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

    PubMed

    Sumerkina, M L

    1997-01-01

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

  8. Localizing epileptic seizure onsets with Granger causality

    NASA Astrophysics Data System (ADS)

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

    2013-09-01

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

  9. Cognitive and behavioural concerns in epileptic children.

    PubMed

    Tamer, S K

    1999-01-01

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

  10. The role of inhibition in epileptic networks.

    PubMed

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

    2015-06-01

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

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

    PubMed

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

    2010-09-01

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

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

    PubMed

    Fábera, P; Mareš, P

    2014-01-01

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

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

    PubMed

    Abdelhalim, K; Smolyakov, V; Genov, R

    2011-10-01

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

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

    NASA Astrophysics Data System (ADS)

    Strange, Bryan A.; Yebra, Mar

    2015-06-01

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

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

    PubMed

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

    2011-04-01

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

  16. Impaired picture recognition in transient epileptic amnesia.

    PubMed

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

    2015-01-01

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

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

    PubMed

    Rossetti, Andrea O; Vulliémoz, Serge

    2016-04-27

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

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

    PubMed

    Haglund, Michael M

    2012-06-01

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

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

    PubMed

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

    2016-09-01

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

  20. Contributions of the hippocampus to feedback learning.

    PubMed

    Dickerson, Kathryn C; Delgado, Mauricio R

    2015-12-01

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

  1. 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.

  2. Oxidative Status in Epileptic Children Using Carbamazepine

    PubMed Central

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

    2015-01-01

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

  3. The Piriform Cortex and Human Focal Epilepsy

    PubMed Central

    Vaughan, David N.; Jackson, Graeme D.

    2014-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2010-02-01

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

  6. Distribution entropy analysis of epileptic EEG signals.

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    1997-08-01

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

  9. Epileptic Seizure Forewarning by Nonlinear Techniques

    SciTech Connect

    Hively, LM

    2001-02-05

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

  10. [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

  11. 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

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

    PubMed

    Rogacheva, T A; Boldyrev, A I

    1986-01-01

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

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

    PubMed

    Bartsch, T; Wulff, P

    2015-11-19

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

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

    PubMed

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

    2016-06-01

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

  15. Hippocampus, microcircuits and associative memory.

    PubMed

    Cutsuridis, Vassilis; Wennekers, Thomas

    2009-10-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Neurogenesis in a young dog with epileptic seizures.

    PubMed

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

    2012-09-01

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

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

    PubMed

    Shbarou, Rolla; Mikati, Mohamad A

    2016-05-01

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

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

    PubMed

    Jehi, Lara; Wyllie, Elaine; Devinsky, Orrin

    2015-10-01

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

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

    PubMed Central

    Li, Jing; Zhen, Xiantong; Liu, Xianzeng

    2014-01-01

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

  2. Two types of isolated epileptic nystagmus: case report

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  5. Stress Effects on the Hippocampus: A Critical Review

    ERIC Educational Resources Information Center

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

    2015-01-01

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

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

    PubMed

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

    2010-12-17

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

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

    PubMed

    Sharma, D; Singh, R

    1995-05-01

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

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

    PubMed

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

    2015-11-01

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

  9. Emergence of semiology in epileptic seizures.

    PubMed

    Chauvel, Patrick; McGonigal, Aileen

    2014-09-01

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

  10. Neural Representations of Location Outside the Hippocampus

    ERIC Educational Resources Information Center

    Knierim, James J.

    2006-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

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

  13. De novo mutations in the classic epileptic encephalopathies

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  15. Cerebrospinal fluid findings after epileptic seizures.

    PubMed

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

    2015-12-01

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

  16. Disposition of sodium valproate in epileptic patients.

    PubMed Central

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

    1978-01-01

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

  17. Asynchronous electrical activity in epileptic seizures

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed

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

    2015-12-01

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

  2. A Novel Dynamic Update Framework for Epileptic Seizure Prediction

    PubMed Central

    Wang, Minghui; Hong, Xiaojun; Han, Jie

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Ruggieri, Víctor L; Arberas, Claudia L

    2013-09-01

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

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

    PubMed

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

    2015-01-01

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

  6. Block term decomposition for modelling epileptic seizures

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

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

    PubMed

    Razali, Salleh Mohd; Yassin, Azhar Mohd

    2008-09-01

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

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

    PubMed

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

    2013-10-01

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

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

    PubMed

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

    2010-01-01

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

  10. Acute transient deafness representing a negative epileptic phenomenon.

    PubMed

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

    2010-07-01

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