Neural basis of global resting-state fMRI activity

Abstract

Functional MRI (fMRI) has uncovered widespread hemodynamic fluctuations in the brain during rest. Recent electroencephalographic work in humans and microelectrode recordings in anesthetized monkeys have shown this activity to be correlated with slow changes in neural activity. Here we report that the spontaneous fluctuations in the local field potential (LFP) measured from a single cortical site in monkeys at rest exhibit widespread, positive correlations with fMRI signals over nearly the entire cerebral cortex. This correlation was especially consistent in a band of upper gamma-range frequencies (40-80 Hz), for which the hemodynamic signal lagged the neural signal by 6-8 s. A strong, positive correlation was also observed in a band of lower frequencies (2-15 Hz), albeit with a lag closer to zero. The global pattern of correlation with spontaneous fMRI fluctuations was similar whether the LFP signal was measured in occipital, parietal, or frontal electrodes. This coupling was, however, dependent on the monkey's behavioral state, being stronger and anticipatory when the animals' eyes were closed. These results indicate that the often discarded global component of fMRI fluctuations measured during the resting state is tightly coupled with underlying neural activity.

Fig. 1.

Simultaneous fMRI and electrophysiology, and data analysis. (A) Position of implanted MR-compatible electrodes in V1 and regions of interest for each monkey. (B) Example of electrophysiological signal (BLP) and fMRI signal (rCBV) measured in this study. Each signal, collected over the course of 30 min, consisted of 700 data points.

Fig. 2.

Cross-correlation between the fMRI (ROI data) and LFP power time courses as a function of LFP constituent frequency. (A) Cross-correlation over all frequencies, expressed as a function of temporal lag (abscissa), averaged over all sessions in three monkeys. Dashed horizontal lines indicate apparent divisions between processes corresponding to frequency ranges. These were classified for further analysis as low (2–15 Hz), middle (15–40 Hz), and high (40–80 Hz). (B) Cross-correlations, for each of the three monkeys, from band-limited power signals derived from each of the three frequency ranges indicated in A.

Fig. 3.

Spatial extent of the correlation between the neural signal in V1 and spontaneous fMRI fluctuations. (A) Correlation maps from one run, obtained at a temporal lag of 7.8 s, are shown for 19 coronal slices in monkey A. The image at the top left corner is from the most posterior slice. The position of the electrode is shown in green on slice 2. Correlation maps from monkeys V and S are shown in Figs. S2 and S3. (B) Correlation maps from the same run as a function of temporal lag are shown on an inflated 3D reconstruction of the monkey's brain. The position of the electrode is shown as a black dot. The temporal coupling between the two signals, as well as the large spatial extent of the correlations, are clearly visible.

Fig. 4.

Spatial extent of the fMRI correlation with high-frequency LFP in frontal area 6d, parietal area 7a, and occipital area V4. (A) In all cases, spatial correlations are bilateral and spread over large swathes of the cerebral cortex. (B) Cross-correlation functions for three electrodes outside V1, for the three frequency ranges. For details, see Fig. 2. Also, see Figs. S8 and S9 for examples of LFP/fMRI correlations with other electrode contacts in each array.

Fig. 5.

Nonstationarity of coupling between fMRI and LFP signal. (A) Example where the use of a sliding window (100 TR) revealed large changes in the fMRI/LFP correlation strength over the course of a run. (B) The corresponding high-frequency LFP power and mean voxel time course from the ROI did not visibly change during this run (top and middle), although the opening and closure of the monkey's eyes appeared linked to the correlation strength (bottom). (C) Analysis of all runs from both monkeys A and S revealed stronger neurovascular coupling when the monkeys’ eyes were mostly (>80% of the time) closed (top) to when they were mostly open (bottom). Monkey V was excluded from this analysis, as her eyes were never closed for more than a few seconds.