Magnetoencephalography of epilepsy with a microfabricated atomic magnetrode

Abstract

Magnetoencephalography has long held the promise of providing a noninvasive tool for localizing epileptic seizures in humans because of its high spatial resolution compared with the scalp EEG. Yet, this promise has been elusive, not because of a lack of sensitivity or spatial resolution but because the large size and immobility of present cryogenic (superconducting) technology prevent long-term telemetry required to capture these very infrequent epileptiform events. To circumvent this limitation, we used Micro-Electro-Mechanical Systems technology to construct a noncryogenic (room temperature) microfabricated atomic magnetometer ("magnetrode") based on laser spectroscopy of rubidium vapor and similar in size and flexibility to scalp EEG electrodes. We tested the magnetrode by measuring the magnetic signature of epileptiform discharges in a rat model of epilepsy. We were able to measure neuronal currents of single epileptic discharges and more subtle spontaneous brain activity with a high signal-to-noise ratio approaching that of present superconducting sensors. These measurements are a promising step toward the goal of high-resolution noninvasive telemetry of epileptic events in humans with seizure disorders.

Keywords: MEG; atomic; epilepsy; magnetomoeter; seizure.

Figure 1.

Theory and operation of the μAM. A, Rubidium (⁸⁷Rb) atoms are spin-polarized by transferring the spin of resonant laser light. B, Precession, or wobble, of electron spin is imparted by external magnetic fields, changing the light transmitted through the atomic vapor. C, Plot of light transmission with magnetic field strength (black; right) and the demodulated signal (gray; left). D, μAM (right) with photodiode removed to expose ⁸⁷Rb vapor cell inside of vacuum package. The μAM is shown compared with a standard scalp EEG electrode (left) and grain of rice (top).

Figure 2.

Simultaneous magnetic and electric recording of spontaneous spikes in the rat. A, Sagittal view of the rat skull (caudal is toward the right) showing positions of the ⁸⁷Rb cell for MEG, and parietal cranial window for ECoG, recording in Experiment 1. The circle with arrows indicates the direction of magnetic fields expected during the negative peak of spikes in the left hemisphere ECoG. At the level of the MEG sensor, the tangential component of the magnetic field is pointed caudally. B, Top, Raw MEG (gray) and ECoG (black) of nonepileptiform ketamine spikes (*). Bottom, Five superimposed ketamine spikes (thin traces) and their average (thick traces). C, Similar to B but showing an example of a single epileptiform spike after focal injection of bicuculline methiodide via the cranial window. Top, Bottom, Single unaveraged spikes. D, Dorsal view showing bilateral placement of magnetrodes over the parietotemporal ridges and bilateral parietal ECoG electrodes. E, Averaged (n = 20) ketamine spikes using the left MEG response peak (arrow) to align the average. The MEG spike (gray) is lateralized to the left hemisphere and attenuated over the right. The averaged ECoG spike is confined to the left hemisphere. F, Similar to E but using the right MEG response peak (arrow) to align averaging. Note a complete shift of the MEG and ECoG response to the right hemisphere. The magnetic field is reversed to a rostral direction, as expected for a right hemisphere equivalent dipole reflecting intradendritic current flowing away from the cortical surface toward the deeper cortical layers.