Broadband local field potentials correlate with spontaneous fluctuations in functional magnetic resonance imaging signals in the rat somatosensory cortex under isoflurane anesthesia

Abstract

Resting-state functional magnetic resonance imaging (fMRI) is widely used for exploring spontaneous brain activity and large-scale networks; however, the neural processes underlying the observed resting-state fMRI signals are not fully understood. To investigate the neural correlates of spontaneous low-frequency fMRI fluctuations and functional connectivity, we developed a rat model of simultaneous fMRI and multiple-site intracortical neural recordings. This allowed a direct comparison to be made between the spontaneous signals and interhemispheric connectivity measured with the two modalities. Results show that low-frequency blood oxygen level-dependent (BOLD) fluctuations (<0.1 Hz) correlate significantly with slow power modulations (<0.1 Hz) of local field potentials (LFPs) in a broad frequency range (1-100 Hz) under isoflurane anesthesia (1%-1.8%). Peak correlation occurred between neural and hemodynamic activity when the BOLD signal was delayed by ~4 sec relative to the LFP signal. The spatial location and extent of correlation was highly reproducible across studies, with the maximum correlation localized to a small area surrounding the site of microelectrode recording and to the homologous area in the contralateral hemisphere for most rats. Interhemispheric connectivity was calculated using BOLD correlation and band-limited LFP (1-4, 4-8, 8-14, 14-25, 25-40, and 40-100 Hz) coherence. Significant coherence was observed for the slow power changes of all LFP frequency bands as well as in the low-frequency BOLD data. A preliminary investigation of the effect of anesthesia on interhemispheric connectivity indicates that coherence in the high-frequency LFP bands declines with increasing doses of isoflurane, whereas coherence in the low-frequency LFP bands and the BOLD signal increases. These findings suggest that resting-state fMRI signals might be a reflection of broadband LFP power modulation, at least in isoflurane-anesthetized rats.

FIG. 1.

(A) Anatomical schematic showing the location of the implanted electrodes. (B) A typical EPI image is shown with two microelectrodes implanted separately in S1FL of left and right hemispheres. There are no obvious artifacts in EPI image due to the electrodes. In traditional seed-based functional connectivity analysis, the seed of S1FL (mean time courses from a few voxels in left S1FL, the solid arrow in C) correlated significantly with the seed region and the opposite S1FL across hemispheres (open arrow in C) during the resting state under isoflurane anesthesia. Color bar represents Peason r.

FIG. 2.

Illustration of the artifacts in electrophysiological recordings induced by magnetic field alternations during the fMRI scan and artifact removal. The original recording from a typical rat under 1% isoflurane is shown (A), including noisy recordings during fMRI imaging (middle dark section). The major artifacts during scanning (solid bar, seen in B and C) are saturated recordings due to gradient field switching). The noise structure (D) can be extracted by averaging all scan cycles of recordings (one of scan period: between red arrows in B). The brief periods of saturation (20 ms of each scan cycle of 500 ms) were refilled with a linear function to maintain continuity (E). After artifact removal, the denoised recordings (F) were used for further analysis. fMRI, functional magnetic resonance imaging.

FIG. 3.

Similar imaging-induced noise profiles in recordings in the case of absent neural activity. During extremely deep anesthesia (isoflurane >2.5%), the neural spontaneous activity was largely suppressed (red). The noise profile (blue) is similar to the original recording (green) due to the largely absent neural activity. The noise structure appears nearly identical to recordings acquired in a moderately anesthetized state where more neural activity is present (Fig. 2D), and includes three components, an initial brief low-amplitude oscillation induced by the RF coil, a period of saturated oscillations related to rapid switching of the gradient, followed by induced oscillations that gradually attenuated to zero over ∼0.2 sec (blue).

FIG. 4.

Synchronized burst activity across hemispheres and spectrum from one rat under 1.5% isoflurane. During isoflurane anesthesia, the neural activity typically showed general suppression with intervening irregular burst activation (red arrow). The bursts of LFP and its power were highly synchronized in SI regions of left (blue) and right (green) hemispheres. The synchronized LFP powers were similar in phase across all LFP frequency bands from 1 to 100 Hz. Correlation between the time courses from each electrode was also calculated for each animal and is shown in Figure 7. LFP, local field potential.

FIG. 5.

Correlation analysis between power modulation of LFPs (1–300 Hz) and BOLD at the recording site of interest. The left panel (A) shows averaged results from all 15 sessions of 7 rats (B). Strong correlation between the BOLD signal and LFPs is observed across the broad range of frequencies. The strongest correlations for all 15 data sets are below 150 Hz. Due to the use of a notch filter at 60 Hz, the recordings at this frequency were attenuated. (C) The mean correlation showed the peak correlation at lags ranging from 2 to 6 sec in the individual data (gray), with the average delay at ∼4 sec time lag for BOLD (mean±standard errors (dark)). BOLD, blood oxygen level dependent.

FIG. 6.

Correlation analysis between power modulation of LFPs (1–100 Hz) and BOLD across a coronal image of the brain. The correlation is spatially restricted to the site of the microelectrode implantation (top panel, each arrow points to recording site with maximum correlation for each electrode; bottom panel, the individual correlation maps from left- or right-electrode recording for all 15 sessions from all 7 rats) and to SI in the contralateral hemisphere. The BOLD time lags are indicated at the left bottom corner of each map. The time courses of power fluctuations of broadband LFPs and 4-sec lagged BOLD (from the voxel with the highest correlation at the recording site) are shown in middle panel.

FIG. 7.

Interhemispheric correlation in power modulation of LFPs across frequency bands. Despite differences in anesthesia levels across 15 study sessions, the pooled data showed a significant negative trend of interhemispheric coherence from high-frequency bands to low-frequency bands (y=−0.0532x+0.5819, R²=0.273, p<0.001).

FIG. 8.

Anesthesia modulation of interhemispheric correlations. The neural suppression induced by 1%–1.8% isoflurane was quantified as neural suppression index (NSI) for each session. The pooled data (15 sessions) show that the high- and low-frequency bands are significantly correlated with NSI, but with different trends: negative for gamma/beta (A–C), but positive for theta/delta (E and F). No correlation was observed for the alpha band (D). The BOLD (G) was in line with theta/delta in response to anesthesia effects.

FIG. 9.

Direct comparison between interhemispheric BOLD correlation and interhemispheric correlation in different bands of LFP. The pooled data (15 sessions) show that interhemispheric correlation in the BOLD signal behaved similarly to interhemispheric correlation in the low-frequency bands of LFPs (theta/delta) when modulated by levels of anesthesia.