Biomedical subjects

Steven J Schiff

Publications and source records attributed to Steven J Schiff.

14 recordsLinked to original sources

PubMed2006

Interneuron and pyramidal cell interplay during in vitro seizure-like events.

Excitatory and inhibitory (EI) interactions shape network activity. However, little is known about the EI interactions in pathological conditions such as epilepsy. To investigate EI interactions during seizure-like events (SLEs), we performed simultaneous dual and triple whole cell and extracellular recordings in pyramidal cells and oriens interneurons in rat hippocampal CA1. We describe a novel pattern of interleaving EI activity during spontaneous in vitro SLEs generated by the potassium channel blocker 4-aminopyridine in the presence of decreased magnesium. Interneuron activity was increased during interictal periods. During ictal discharges interneurons entered into long-lasting depolarization block (DB) with suppression of spike generation; simultaneously, pyramidal cells produced spike trains with increased frequency (6-14 Hz) and correlation. After this period of runaway excitation, interneuron postictal spiking resumed and pyramidal cells became progressively quiescent. We performed correlation measures of cell-pair interactions using either the spikes alone or the subthreshold postsynaptic interspike signals. EE spike correlation was notably increased during interneuron DB, whereas subthreshold EE correlation decreased. EI spike correlations increased at the end of SLEs, whereas II subthreshold correlations increased during DB. Our findings underscore the importance of complex cell-type-specific neuronal interactions in the formation of seizure patterns.

Action Potentials↗

PubMed2005

Neuronal spatiotemporal pattern discrimination: the dynamical evolution of seizures.

We developed a modern numerical approach to the multivariate linear discrimination of Fisher from 1936 based upon singular value decomposition that is sufficiently stable to permit widespread application to spatiotemporal neuronal patterns. We demonstrate this approach on an old problem in neuroscience--whether seizures have distinct dynamical states as they evolve with time. A practical result was the first demonstration that human seizures have distinct initiation and termination dynamics, an important characterization as we seek to better understand how seizures start and stop. Our approach is broadly applicable to a wide variety of neuronal data, from multichannel EEG or MEG, to sequentially acquired optical imaging data or fMRI.

Adult↗

PubMed2005

Control of traveling waves in the Mammalian cortex.

We experimentally confirmed predictions that modulation of the neuronal threshold with electrical fields can speed up, slow down, and even block traveling waves in neocortical slices. The predictions are based on a Wilson-Cowan-type integro-differential equation model of propagating neocortical activity. Wave propagation could be modified quickly and reversibly within targeted regions of the network. To the best of our knowledge, this is the first example of direct modulation of the threshold to control wave propagation in a neural system.

Action Potentials↗

PubMed2005

Multivariate linear discrimination of seizures.

OBJECTIVE: To discriminate seizures from interictal dynamics based on multivariate synchrony measures, and to identify dynamics of a pre-seizure state. METHODS: A linear discriminator was constructed from two different measures of synchronization: cross-correlation and phase synchronization. We applied this discriminator to a sequence of seizures recorded from the intracranial EEG of a patient monitored over 6 days. RESULTS: Surprisingly, we found that this bivariate measure of synchronization was not a reliable seizure discriminator for 7 of 9 seizures. Furthermore, the method did not appear to reliably detect a pre-seizure state. An association between anti-convulsant dosage, frequency of clinical seizures, and discriminator performance was noted. CONCLUSIONS: Using a bivariate measure of synchronization failed to reliably differentiate seizures from non-seizure periods in these data, nor did such methods show reliable detection of a synchronous pre-seizure state. The non-stationary variables of decreasing antiepileptic medication (without available serum concentration measurements), and concomitant increasing seizure frequency contributed to the difficulties in validating a seizure prediction tool on such data. SIGNIFICANCE: The finding that these seizures were not a simple reflection of increasing synchronization in the EEG has important implications. The non-stationary characteristics of human post-implantation intracranial EEG is an inherent limitation of pre-resection data sets.

Anticonvulsants↗

PubMed2005

A model of the effects of applied electric fields on neuronal synchronization.

We examine the effects of applied electric fields on neuronal synchronization. Two-compartment model neurons were synaptically coupled and embedded within a resistive array, thus allowing the neurons to interact both chemically and electrically. In addition, an external electric field was imposed on the array. The effects of this field were found to be nontrivial, giving rise to domains of synchrony and asynchrony as a function of the heterogeneity among the neurons. A simple phase oscillator reduction was successful in qualitatively reproducing these domains. The findings form several readily testable experimental predictions, and the model can be extended to a larger scale in which the effects of electric fields on seizure activity may be simulated.

Action Potentials↗

PubMed2005

Dangerous phase.

"Use a quiet reference." How many times have we heard this mantra during training or practice, interpreting electroencephalogram (EEG) tracings, or implanting intracranial electrodes? How many of us have used common reference EEG for synchrony studies in recent years? Far too many.Perhaps one source of this problem is the number 104. This is the relatively small number of citations to the reference Fein et al. (1988), which should have put to rest any further use of referential EEG for coherence measurements. And in retrospect, a more careful reading by us of Nunez's (1981) text would have instructed us not to do this. How such warnings have managed to escape integration into common knowledge and practice is troublesome. Electrical potentials are all measured with respect to other potentials. Technically, a potential difference is calculated by integrating the electrical field over a given path from one place to another in EEG terms, we mea sure a potential with respect to another potential, measured at one or more electrodes. All EEG potential measurements reflect the paths used to measure those potentials, and do not directly reflect localized regions of the brain beneath one electrode. Worse, in scalp EEG, the layers of cerebrospinal fluid, dura, skull, and scalp serve to smooth, filter, spread out, and redirect currents generated within the brain so that the measured scalp potentials bear a rather tenuous relationship to the underlying (presumably dipole) current sources. In calculating coherence, it is easy to show that if the potential differences are all made with respect to a common reference, then the amplitude of the reference can dominate the coherence estimate (Fein et al., 1988). In recent years, phase synchronization has been increasingly applied to analyze the dynamics of nonlinear systems (Pikovsky et al., 2000). In Guevara et al. (in this issue), we see the extension of Fein's results for phase coherency. The geometry of Fig. 1 in Guevara et al. should be imprinted on all of us the amplitude of a common reference can dominate the calculated phase syn chronization. There is far too much literature within the past decade that calculated phase synchronization from common referenced EEG. The good news is that the fix to remove common reference artifacts is simple. The bad news is that the interpretation of reference- free synchronization results from brain signals requires considerable caution.

Algorithms↗

PubMed2004

Spiral waves in disinhibited mammalian neocortex.

Spiral waves are a basic feature of excitable systems. Although such waves have been observed in a variety of biological systems, they have not been observed in the mammalian cortex during neuronal activity. Here, we report stable rotating spiral waves in rat neocortical slices visualized by voltage-sensitive dye imaging. Tissue from the occipital cortex (visual) was sectioned parallel to cortical lamina to preserve horizontal connections in layers III-V (500-mum-thick, approximately 4 x 6 mm(2)). In such tangential slices, excitation waves propagated in two dimensions during cholinergic oscillations. Spiral waves occurred spontaneously and alternated with plane, ring, and irregular waves. The rotation rate of the spirals was approximately 10 turns per second, and the rotation was linked to the oscillations in a one-cycle- one-rotation manner. A small (<128 mum) phase singularity occurred at the center of the spirals, about which were observed oscillations of widely distributed phases. The phase singularity drifted slowly across the tissue ( approximately 1 mm/10 turns). We introduced a computational model of a cortical layer that predicted and replicated many of the features of our experimental findings. We speculate that rotating spiral waves may provide a spatial framework to organize cortical oscillations.

Action Potentials↗

PubMed2004

Analytical coupling detection in the presence of noise and nonlinearity.

A rigorous analytical approach is developed to test for the existence of a continuous nonlinear functional relationship between systems. We compare the application of this nonlinear local technique to the existing analytical linear global approach in the setting of increasing additive noise. For natural systems with unknown levels of noise and nonlinearity, we propose a general framework for detecting coupling. Lastly, we demonstrate the applicability of this method to detect coupling between simultaneous, experimentally measured, intracellular voltages between neurons within a mammalian neuronal network.

Animals↗

PubMed2003

Interplay of electroencephalogram phase and auditory-evoked neural activity.

Auditory-evoked potentials (AEPs) were triggered in real time as a function of ongoing electroencephalogram (EEG) phase. Phase triggering on-line or retrospective phase-selective averaging introduces phase artifacts such as spurious troughs or peaks, which mask mid-latency and affect the amplitude of late AEPs. We developed a method to control for phase artifacts by phase-selective averaging of trials, recorded without stimulation, and used this to uncover a previously unknown phase dependency of AEPs. Not only are such findings inconsistent with the standard additive evoked potential model, but we identified clear neural correlates at fixed latencies, which are inconsistent with the recently proposed phase-resetting model. Our findings suggest that a new conceptualization is required to account for the interplay between the correlates of neural-evoked activity and modulation of ongoing EEG that together constitute evoked potentials.

Acoustic Stimulation↗

PubMed2003

Sensitivity of neurons to weak electric fields.

Weak electric fields modulate neuronal activity, and knowledge of the interaction threshold is important in the understanding of neuronal synchronization, in neural prosthetic design, and in the public health assessment of environmental extremely low frequency fields. Previous experimental measurements have placed the threshold between 1 and 5 mV/mm, although theory predicts that elongated neurons should have submillivolt per millimeter sensitivity near 100 microV/mm. We here provide the first experimental confirmation that neuronal networks are detectably sensitive to submillivolt per millimeter electrical fields [Gaussian pulses 26 msec full width at half-maximal, 140 microV/mm root mean square (rms), 295 microV/mm peak amplitude], an order of magnitude below previous findings, and further demonstrate that these networks are more sensitive than the average single neuron threshold (185 microV/mm rms, 394 microV/mm peak amplitude) to field modulation.

Action Potentials↗

PubMed2003

In vivo modulation of hippocampal epileptiform activity with radial electric fields.

PURPOSE: Electric field stimulation can interact with brain activity in a subthreshold manner. Electric fields have been previously adaptively applied to control seizures in vitro. We report the first results from establishing suitable electrode geometries and trajectories, as well as stimulation and recording electronics, to apply this technology in vivo. METHODS: Electric field stimulation was performed in a rat kainic acid injection seizure model. Radial electric fields were generated unilaterally in hippocampus from an axial depth electrode. Both sinusoidal and multiphasic stimuli were applied. Hippocampal activity was recorded bilaterally from tungsten microelectrode pairs. Histologic examination was performed to establish electrode trajectory and characterize lesioning. RESULTS: Electric field modulation of epileptiform neural activity in phase with the stimulus was observed in five of six sinusoidal and six of six multiphasic waveform experiments. Both excitatory and suppressive modulation were observed in the two experiments with stimulation electrodes most centrally placed within the hippocampus. Distinctive modulation was observed in the period preceding seizure-onset detection in two of six experiments. Short-term histologic tissue damage was observed in one of six experiments associated with high unbalanced charge delivery. CONCLUSIONS: We demonstrated in vivo electric field modulation of epileptiform hippocampal activity, suggesting that electric field control of in vivo seizures may be technically feasible. The response to stimulation before seizure could be useful for triggering control systems, and may be a novel approach to define a preseizure state.

Amplifiers, Electronic↗

PubMed2002

Decreased neuronal synchronization during experimental seizures.

Synchronization between CA1 pyramidal neurons was studied using dual-cell patch-clamp techniques simultaneous with an extracellular measurement of network activity. We explored various linear and nonlinear methods to detect weak synchronization in this network, using cross-correlation, mutual information in one and two dimensions, and phase correlation in both broad and narrow band. The linear and nonlinear methods demonstrated different patterns of sensitivity to detect synchrony in this network, depending on the dynamical state of the network. Bursts in 4-amino-pyridine (4AP) were highly synchronous events. Unexpectedly, seizure-like events in 4AP were desynchronous events, both in comparison with interictal periods preceding the seizure without bursts (cut Schaffer collateral tract) and in comparison with bursts preceding the seizures (intact Schaffer collateral tract). The finding that seizure-like events are associated with desynchronization in such networks is consistent with recent theoretical work, suggesting that asynchrony is necessary to maintain a high level of activity in neuronal networks for sustained periods of time and that synchrony may disrupt such activity.

4-Aminopyridine↗

PubMed2002

Limits to the experimental detection of nonlinear synchrony.

Chaos synchronization is often characterized by the existence of a continuous function between the states of the components. However, in coupled systems without inherent symmetries, the synchronization set can be extremely complicated. We describe and illustrate three typical complications that can arise, and we discuss how existing methods for detecting synchronization will be hampered by the presence of these features.

Models, Biological↗

PubMed2002

Failure of single-unit neuronal activity to differentiate globus pallidus internus and externus in Parkinson disease.

OBJECT: The authors examine the validity of single-unit neuronal recordings as a method of differentiating the globus pallidus internus (GPi) from the GP externus (GPe) in Parkinson Disease. METHODS: One hundred twenty-eight recordings of apparent single-unit activity used to help guide final electrode placement in eight patients who underwent pallidotomy were analyzed using sophisticated spike sorting methods, and 185 neurons were characterized for mean firing frequency and percent of firing within bursts. In addition, the total spectral power was calculated on the full measured waveform for each of 128 samples without spike sorting. No correlation was identified between these measures of neuronal activity and depth within the GP. CONCLUSIONS: These results call into question the validity of relying on single-unit activity and microelectrode recordings in the operating room to localize lesion or electrode placement within the GPi during stereotactic pallidal surgery.

Action Potentials↗