In Vivo Magnetic Recording of Neuronal Activity

Abstract

Neuronal activity generates ionic flows and thereby both magnetic fields and electric potential differences, i.e., voltages. Voltage measurements are widely used but suffer from isolating and smearing properties of tissue between source and sensor, are blind to ionic flow direction, and reflect the difference between two electrodes, complicating interpretation. Magnetic field measurements could overcome these limitations but have been essentially limited to magnetoencephalography (MEG), using centimeter-sized, helium-cooled extracranial sensors. Here, we report on in vivo magnetic recordings of neuronal activity from visual cortex of cats with magnetrodes, specially developed needle-shaped probes carrying micron-sized, non-cooled magnetic sensors based on spin electronics. Event-related magnetic fields inside the neuropil were on the order of several nanoteslas, informing MEG source models and efforts for magnetic field measurements through MRI. Though the signal-to-noise ratio is still inferior to electrophysiology, this proof of concept demonstrates the potential to exploit the fundamental advantages of magnetophysiology.

Keywords: MEG; Magnetic fields; magnetic sensors; magnetoencephalography; spin electronics.

Figure 1. Magnetrode description and magnetic characteristics

(A) Scanning Electron Microscopy picture of a magnetrode containing 2 GMR elements, each with a meandering configuration. The elements are deposited on a 200 µm thick silicon substrate that is 150 µm wide before narrowing at an 18° angle towards the tip. The sensitive direction is in the plane of the elements and orthogonal to the long axis of the tip. A platinum electrode (blue square) has additionally been deposited, but no recordings were achieved with it. Scale bar 100 µm. (B) Output voltage of the GMR sensor as a function of the magnetic field. The sensor is used for very weak magnetic fields around zero, which lead to outputs within the steep linear part of the curve. In the linear part, the slope is 1.8%/mT. (C) Equivalent-field noise spectral density S_B from 1 Hz to 10 kHz of the corresponding probe for 500 mV and 1 V peak-to-peak AC voltage of the GMR element. To obtain S_B, the output voltage is converted in field-equivalent by applying a calibrated magnetic signal at 30 Hz. See also Figure S1.

Figure 2. Experimental setup

Recordings were performed in primary visual cortex of the anesthetized cat. To activate the area, a visual stimulus was applied directly to the contralateral eye using blue LED light. The magnetrode, containing the GMR sensor, was positioned within visual cortex. A tungsten electrode was targeted to be less than 1 mm from the magnetrode, to simultaneously obtain an independent electric recording. The zoomed-in inset illustrates the expected configuration of the magnetrode and electrode in the neuropil. The output signal from the GMR sensor was demodulated. Subsequently, the GMR and the electrode signal were amplified, filtered and digitized.

Figure 3. GMR output in AC mode to electric and magnetic field inputs

(A) The black line shows in arbitrary units the magnetic field input to the GMR, generated by a respective phantom. The input signal was an exponential chirp, i.e. a sinusoidal current with frequency varying exponentially from 1 Hz to 2 kHz. The GMR output was demodulated, and the in-phase output is shown in red, the out-of-phase output in green. Magnetic input is expected to be reflected primarily in the in-phase output, which is confirmed. (B) Same as (A), but with an electric field input (black line, in arbitrary units). Electric field input is expected to be reflected more in the out-of-phase output, which is confirmed, particularly for higher frequencies. See also Figure S2.

Figure 4. Validation of the magnetic nature of in vivo recordings

(A) GMR output after in-phase (red) and out-of-phase (green) demodulation, which would be expected (based on the phantom measurements shown in Fig. 3), if the input were a purely electric field with the waveform of an ERP (black). (B) Same as (A), if the input were a purely magnetic field with the same waveform. (C) Experimentally observed GMR output after in-phase (red) and out-of-phase (green) demodulation. The ERP recorded simultaneously from an independent tungsten electrode is shown in black. The ERP and the GMR outputs are averages over 1000 stimulus repetitions. See also Figure S2.

Figure 5. Comparison between simultaneously recorded event-related potentials (ERPs) and event-related fields (ERFs)

(A) ERF obtained in cat 1 by averaging the GMR in-phase output over 1000 stimulus repetitions. The dashed vertical lines indicate onset and offset of the 100 ms long visual stimulus. (B) ERP obtained simultaneously by averaging the signal from an independent tungsten electrode, over the same 1000 stimulus repetitions. For both the ERF and the ERP, the gray shaded regions show ±1 SEM. The error region of the ERP can be visually appreciated by magnifying the figure. (C) Direct comparison of the waveforms of the ERF (red) and the ERP (green). (D) Pearson correlation coefficient between the ERF and the ERP as a function of time lag. (E–H) Same as (A–D), but for a recording session in cat 2. (I–L) Same as (E–H), but for a separate recording session in cat 2, using a 500 ms long visual stimulus.

Figure 6. Evaluation of signal quality

(A) Signal-to-noise ratio (SNR) of the ERF as a function of the number of trials that were averaged. As specified in the color legend, different colors refer to different recording sessions, and color saturation indicates significance. (B) Same as (A), but zoomed in on the transition to significance. (C) Same as (A), but for the simultaneously recorded ERP. (D) Pearson correlation coefficient between a template ERF averaged over 500 trials and a subset-ERF averaged over the number of trials specified on the x-axis. Template and subset ERF always averaged non-overlapping sets of trials. (E) Same as (D), but enlarged around the transition to significance. (E) Same as (D), but for the simultaneously recorded ERP. Note that metrics for ERFs and ERPs are shown with different y-axis scales. The correlation values for ERPs of cat 2A and cat 2B (F) are very similar and largely overlap.