Direct magnetic resonance detection of neuronal electrical activity

Abstract

Present noninvasive neuroimaging methods measure neuronal activity indirectly, via either cerebrovascular changes or extracranial measurements of electrical/magnetic signals. Recent studies have shown evidence that MRI may be used to directly and noninvasively map electrical activity associated with human brain activation, but results are inconclusive. Here, we show that MRI can detect cortical electrical activity directly. We use organotypic rat-brain cultures in vitro that are spontaneously active in the absence of a cerebrovascular system. Single-voxel magnetic resonance (MR) measurements obtained at 7 T were highly correlated with multisite extracellular local field potential recordings of the same cultures before and after blockade of neuronal activity with tetrodotoxin. Similarly, for MR images obtained at 3 T, the MR signal changed solely in voxels containing the culture, thus allowing the spatial localization of the active neuronal tissue.

Fig. 1.

EEG showing the spontaneous synchronized neuronal activity in one culture. (a) Net activity exhibited in the culture over a period of 1,000 s (≈17 min) obtained from averaging the 60 MEA channels. (b) Power spectrum of the EEG shown in a. High power associated with activity is concentrated in the <15 Hz range. The power spectrum range is 0–500 Hz (sampling at 1 kHz); however, for visibility, only 0–100 Hz is shown.

Fig. 2.

EEG and MR spectra obtained from two cultures (a and b) plus the control (c). To compare between the MR and EEG spectra, only the 0–5 Hz frequency range is shown for the EEG. (a and b) Signal power is reduced after TTX administration (green vs. black lines). Residual peaks in the TTX phase spectra, also present in the PRE state, are possibly due to systematic noise. (c) For the control experiment, there was no significant change in signal power after TTX administration.

Fig. 3.

Comparison between EEG and MR data. (a) Signal power decrease (0–5 Hz) between PRE and TTX states, for MR magnitude (+), and MR phase (Δ) vs. EEG (n = 5, plus control). (b) Spectral center frequency (spectral centroid 0–5 Hz) for MR magnitude (+) and MR phase (Δ) vs. EEG (n = 5, plus control). The control experiment was performed with no culture on the MEA, but all other conditions were identical.

Fig. 4.

Imaging results obtained for one culture. (a) Single-voxel phase and magnitude spectra for the culture region. (b–d) Single-voxel phase and magnitude spectra for three artificial cerebrospinal fluid (ACSF) locations. A peak corresponding to the culture site is observed solely in the PRE phase spectrum, marked as A (≈0.14 Hz), possibly representing the activation burst frequency of the culture. The spectral peak marked as C corresponds to the scanner cooling-pump frequency and is present in all conditions. (e) Structural fast-spin-echo image obtained during the same MR session. (f and g) Phase map (f) and magnitude map (g), showing the difference in signal power between the PRE and TTX conditions for peak A. The spectra shown in a correspond to a voxel in the culture area indicated by the box in e and f. The spectra shown in (b–d) are marked by orange arrows on the phase map (clockwise from culture). The increased signal power for peak A is localized on the culture in the phase map, seen also in the overplot of A on the anatomical image in e. The high-intensity region indicated by the white arrow (f, upper left) reflects elevated signal power in the PRE state at all frequencies, possibly due to hardware instabilities or imperfect shimming.