Collapsing perisomatic inhibition leads to epileptic fast ripple oscillations caused by pseudosynchronous firing of CA3 pyramidal neurons.

Reduced Spike-Timing Reliability Correlates with the Emergence of Fast Ripples in the Rat Epileptic Hippocampus

Neurons Skip a Beat during Fast Ripples

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.

We have demonstrated the loss of transverse spatial coherence of an atomic wave function after a single spontaneous emission. ${\mathrm{He}}^{*}$ atoms were both diffracted and excited by a standing light wave with a variable period. After the interaction, the excited atoms decay by a single spontaneously emitted photon. By changing the period of the standing light wave, we have mapped the loss of spatial coherence as a function of the transverse coordinate. By detecting the emitted photon one could "erase" the position information available and recover the transverse coherence in a correlation experiment, or realize a Heisenberg microscope.

Spontaneous fluctuations in neuronal activity emerge at many spatial and temporal scales in cortex. Population measures found these fluctuations to organize as scale-invariant neuronal avalanches, suggesting cortical dynamics to be critical. Macroscopic dynamics, though, depend on physiological states and are ambiguous as to their cellular composition, spatiotemporal origin, and contributions from synaptic input or action potential (AP) output. Here, we study spontaneous firing in pyramidal neurons (PNs) from rat superficial cortical layers in vivo and in vitro using 2-photon imaging. As the animal transitions from the anesthetized to awake state, spontaneous single neuron firing increases in irregularity and assembles into scale-invariant avalanches at the group level. In vitro spike avalanches emerged naturally yet required balanced excitation and inhibition. This demonstrates that neuronal avalanches are linked to the global physiological state of wakefulness and that cortical resting activity organizes as avalanches from firing of local PN groups to global population activity.DOI: http://dx.doi.org/10.7554/eLife.07224.001

A method for the topographical identification and quantification of high frequency oscillations in intracranial electroencephalography recordings

In a previous paper, the authors developed a technique known as Vector Linear Prediction (VLP) which achieved super-resolution processing for polarimetric SAR tomography. In this paper, the performance of this multivariate super-resolution processing technique is investigated. Both simulations and field data are used to assess the limitations of this technique due to the loss of spatial and polarimetric coherence. The model assumes two scattering centers in each image pixel. The study shows that if one component remains linearly polarized, while the other is fully depolarized, then meaningful interferometric information can still be retrieved for the linearly polarized scattering center. However, if the depolarized component is also spatially decorrelated (loss of spatial coherence), then the interferometric phase estimates of both components are prone to significant errors. The field data is used to verify and validate the observations obtained with the simulations.

WORKING FORUM -- PANEL DISCUSSIONCOMPONENTS RESEARCH DIRECTIONSModerator: Leo Baiser, CBS LaboratoriesPanel: Robert D. Anwyl, Eastman Kodak CompanyGeorge D. Cody, RCA LaboratoriesVernon Fowler, GTE LaboratoriesRobert Hopkins, Tropel, Inc.Theodore Maiman, Laser Video, Inc.R. M. Montgomery, Harris CorporationThe transcript opens during a discussionof internally scanned lasers, shortlyafter the start of the session.V. FOWLER: When you internally scan alaser, you inevitably wind up with adevice that has somewhat less powercapability and efficiency than withexternal modulation, some loss of co-herence and some loss of resolvingpower or spatial coherence. The bestway to design a system with technologythat is available today is in building -block fashion: get a good laser, pre-serve its spatial coherence, get a goodmodulator, do a good job at hanging thepieces together so the resolution ispreserved throughout the system; inother words, hang the system on thiscoherent beam. It's not necessarilythe only way to go. I think that inthe future if we come up with a singledevice that serves multiple functions,it would be nice to get around the costof that modulator, for example.

Network mechanisms for fast ripple activity in epileptic tissue

Hub GABA Neurons Mediate Gamma-Frequency Oscillations at Ictal-like Event Onset in the Immature Hippocampus

Information processing in neuronal networks involves the recruitment of selected neurons into coordinated spatiotemporal activity patterns. This sparse activation results from widespread synaptic inhibition in conjunction with neuron-specific synaptic excitation. We report the selective recruitment of hippocampal pyramidal cells into patterned network activity. During ripple oscillations in awake mice, spiking is much more likely in cells in which the axon originates from a basal dendrite rather than from the soma. High-resolution recordings in vitro and computer modeling indicate that these spikes are elicited by synaptic input to the axon-carrying dendrite and thus escape perisomatic inhibition. Pyramidal cells with somatic axon origin can be activated during ripple oscillations by blocking their somatic inhibition. The recruitment of neurons into active ensembles is thus determined by axonal morphological features.

Fast ripples are a type of transient high-frequency oscillations recorded from the epileptogenic regions of the hippocampus and the temporal cortex of epileptic humans and rodents. These events presumably reflect hypersynchronous bursting of pyramidal cells. However, the oscillatory spectral content of fast ripples varies from 250 to 800 Hz, well above the maximal firing frequency of most hippocampal pyramidal neurons. How such high-frequency oscillations are generated is therefore unclear. Here, we combine computational simulations of fast ripples with multisite and juxtacellular recordings in vivo to examine the underlying mechanisms in the hippocampus of epileptic rats. We show that populations of bursting cells firing individually at 100-400 Hz can create fast ripples according to two main firing regimes: (1) in-phase synchronous firing resulting in "pure" fast ripples characterized by single spectral peaks that reflect single-cell behavior and (2) out-of-phase firing that results in "emergent" fast ripples. Using simulations, we found that fast ripples generated under these two different regimes can be quantitatively separated by their spectral characteristics, and we took advantage of this separability to examine their dynamics in vivo. We found that in-phase firing can reach frequencies up to 300 Hz in the CA1 and up to 400 Hz in the dentate gyrus. The organization of out-of-phase firing is determined by firing delays between cells discharging at low frequencies. The two firing regimes compete dynamically, alternating randomly from one fast ripple event to the next, and they reflect the functional dynamic organization of the different regions of the hippocampus.

Epilepsy treatment with anti-seizure medications (ASMs) is based on careful assessment of the balance between the likelihood of further seizures and the risk of side effects of treatment. However, there is currently no established biomarker to ascertain seizure control status with ASMs. High-frequency oscillations (HFOs), transient bursts of EEG activity with frequencies beyond 80 Hz, are a new and promising noninvasive epilepsy biomarker. We compared the risk of scalp HFO appearance between pediatric patients with good and poor seizure control by treatment with ASMs. A total of 72 epilepsy patients (aged 0-18 years, 39 males) with good and poor seizure control with ASMs participated in this study. We applied a validated automated detector to determine HFO and spike. We calculated the odds ratios (ORs) for scalp HFO and spike appearance according to seizure control status by multiple logistic regression analysis. Scalp HFO was seen more commonly and with a significantly higher detection rate in patients with poor seizure control as compared with patients with good seizure control for both ripple and fast ripple. These significant associations were found for both focal and generalized epilepsy. The ORs for scalp HFO appearance adjusted for confounding factors were significantly higher in patients with poor seizure control compared to those with good seizure control (ripple: OR [95% CI] = 11.91 [2.21-64.30], p = 0.004; fast ripple: 4.98 [1.03-24.09], p = 0.046). There were no significant associations between spike appearance and seizure control status. We found an increased risk of scalp HFO appearance in patients with poor seizure control. The results of this study support that scalp HFO is associated with patients having frequent seizures after treatment in both ripple and fast ripple. This study analyzed scalp high-frequency oscillations and spikes in pediatric patients with various types of epilepsy who were being treated using ASMs. The results showed that an increased risk of scalp HFO appearance was observed in patients with poor seizure control compared to those with good seizure control. These findings were observed in both the ripple (80-250 Hz) and fast ripple (250-500 Hz) bands. The scalp HFO is associated with patients having frequent seizures after treatment in both ripple and fast ripple.

Visual Deprivation Suppresses L5 Pyramidal Neuron Excitability by Preventing the Induction of Intrinsic Plasticity

Ripple oscillations (80–200 Hz) in the normal hippocampus are involved in memory consolidation during rest and sleep. In the epileptic brain, increased ripple and fast ripple (200–600 Hz) rates serve as a biomarker of epileptogenic brain. We report that both ripples and fast ripples exhibit a preferred phase angle of coupling with the trough-peak (or On-Off) state transition of the sleep slow wave in the hippocampal seizure onset zone (SOZ). Ripples on slow waves in the hippocampal SOZ also had a lower power, greater spectral frequency, and shorter duration than those in the non-SOZ. Slow waves in the mesial temporal lobe modulated the baseline firing rate of excitatory neurons, but did not significantly influence the increased firing rate associated with ripples. In summary, pathological ripples and fast ripples occur preferentially during the On-Off state transition of the slow wave in the epileptogenic hippocampus, and ripples do not require the increased recruitment of excitatory neurons.