Neural activity can propagate as waves in the brain. Such waves of activity may be important in processing of sensory information when awake, are present during deep sleep, and may be involved with spread of epileptic seizures. In this present paper, we predicted from a mathematical model of wave propagation, then confirmed experimentally, that externally applied electrical fields can slow such waves sufficiently to stop them. Specifically, we demonstrated that by using electric fields to modulate neuronal excitability, we can speed up, slow down and even halt propagation of seizure-like waves of activity in rat brain slices. An important application of such control over the propagation of waves of activity in human brain would allow for the development of implantable seizure control electrical devices that can be used to contain seizure activity within a small localized region and thereby prevent such seizures from spreading throughout the brain.
Abstract: We experimentally confirmed predictions that modulation of 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 integrodifferential 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 threshold to control wave propagation in a neural systems.
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 successfulin 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.
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.
Weak electric fields modulate neuronal activity, and knowlede of th 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 perdicts that elongated neurons should have submillivolt per millimeter sensitivity near 100 mV/mm. We here provide the first experimental confirmation that neuronal networks are detectably sensitive to submillivolt per millimeter electric fields [Gaussian pulses 26msec full width at half-maximal, 140 mV/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 mV/mm peak amplitude) to field modulation.
Motived by the observation that applied fields modulate hippocampal seizures, and that seizures may be asynchronous, we modeled synaptically-coupled 2-compartment hippocampal pyramidal neurons embedded within an electrically resistive lattice in order to examine network sychronization properties under the influence of externally applied electric fields. Excitatory electric fields were shown to synchronize or desynchronize the network dependin on the natural frequency mismatch between the neurons. Such frequency mismatch was found to decrease as a function of increasing electric field amplitude. These findings provide testable hypotheses for future seizure control experiments.
We describe a novel method of adaptively controlling epileptic seizure-like events in hippocampal brain slices using electric fields. Extracellular neuronal activity is continuously recorded during field application through differential extracellular recording techniques, and the applied electric field strength is continuously updated using a computer-controlled proportional feedback algorithm. This approach appears capable of sustained amelioration of seizure events in this preparation when used with negative feedback. Seizures can be induced or enhanced by using fields of opposite polarity through positive feedback. In negative feedback mode, such findings may offer a novel technology for seizure control. In positive feedback mode, adaptively applied electric fields may offer a more physiological means of neural modulation for prosthetic purposes than previously possible.
- 1. The effects of relatively small external DC electric fields on synchronous activity in CA1 and CA3 from transverse and longitudinal type hippocampal slices were studied.
- 2. To record neuronal activity during significant field changes, differential DC amplification was employed with a reference electrode aligned along an isopotential with the recording electrode.
- 3. Suppression of epileptiform activity was observed in 31 of 33 slices independent of region studied and type of slice but was highly dependent on field orientation with respect to the apical dendritic-somatic axis.
- Modulation of neuronal activity in these experiments was readily observed at field strengths <5-10 mv/mm. Suppression was seen with the field oriented (positive to negative potential) from the soma to the apical dentrites.
- In vivo application of these results may be feasible.