Infraslow LFP correlates to resting-state fMRI BOLD signals

Abstract

The slow fluctuations of the blood-oxygenation-level dependent (BOLD) signal in resting-state fMRI are widely utilized as a surrogate marker of ongoing neural activity. Spontaneous neural activity includes a broad range of frequencies, from infraslow (<0.5 Hz) fluctuations to fast action potentials. Recent studies have demonstrated a correlative relationship between the BOLD fluctuations and power modulations of the local field potential (LFP), particularly in the gamma band. However, the relationship between the BOLD signal and the infraslow components of the LFP, which are directly comparable in frequency to the BOLD fluctuations, has not been directly investigated. Here we report a first examination of the temporal relation between the resting-state BOLD signal and infraslow LFPs using simultaneous fMRI and full-band LFP recording in rat. The spontaneous BOLD signal at the recording sites exhibited significant localized correlation with the infraslow LFP signals as well as with the slow power modulations of higher-frequency LFPs (1-100 Hz) at a delay comparable to the hemodynamic response time under anesthesia. Infraslow electrical activity has been postulated to play a role in attentional processes, and the findings reported here suggest that infraslow LFP coordination may share a mechanism with the large-scale BOLD-based networks previously implicated in task performance, providing new insight into the mechanisms contributing to the resting state fMRI signal.

Fig. 1

Time-lagged correlation between BOLD and infraslow LFP during spontaneous activity. Correlation was calculated between infraslow LFPs (< 0.1 Hz in ISO; < 0.25 Hz in DMED), left or right hemisphere at S1FL, and BOLD (< 0.1 Hz in ISO; < 0.25 Hz in DMED) signals from each voxel in the imaged slice of the brain. The results for the two anesthetic groups are shown separately in the top row (under ISO) and the bottom row (under DMED). Time-lagged correlation maps of representative results are shown on the left, with average ROI results from all rats on the right. The arrow head indicates the ROI of the recording site, which exhibits the highest correlation between infraslow LFP and BOLD at 4 sec lag under ISO (A1 and A2) and 2.5 sec lag under DMED (A2 and B2). The hemisphere opposite the recording site also shows high BOLD/infraslow LFP correlation. The number at the left bottom corner of each brain represents the BOLD time lag (sec). The average correlation values (mean ± SEM) are plotted against time lag on the right column (B1, ISO, n = 6 rats; B2, DMED, n = 7 rats), showing BOLD/infraslow LFP correlation as a function of time lag. The stars indicate significant differences from the mean value of the first two points (p < 0.05, paired t-test on z values, z=0.5*ln((1+r)/(1−r)), corrected for multiple comparisons). The significant BOLD/infraslow LFP correlation (FDR corrected, p < 0.05) at the peak time lag for each group is shown in warm colors (B1 and B2). The left side of the brain is on the left side of the image. Color bar values represent Pearson r.

Fig. 2

Simultaneous DC recording from CP during fMRI. The recording site in the caudate putamen (CP) is illustrated at left panel. The BOLD/infraslow LFP correlation results with varied BOLD lags (−2.5 sec to 9.5 sec) are shown in the right panel. The maximum correlation is observed in bilateral CP when the BOLD signal is delayed by 2.5 sec relative to infraslow LFP under dexmedetomidine. The left side of the brain is on the left side of the image.

Fig. 3

Frequency contribution to BOLD/infraslow LFP coupling. Coherence analysis showed high BOLD/infraslow LFP coherence in the low frequencies (blue, mean ± SEM), peaking below 0.1 Hz in ISO anesthesia (A) and below 0.25 Hz in DMED (B). The same analysis was performed with time-reversed infraslow LFP signals as a control. The BOLD/time-reversed infraslow LFP coherence for each frequency is plotted in gray (mean ± SEM). The significant difference (p < 0.05, corrected) between the coherences of real data and the control are indicated with a star (*). All significant differences are around coherence peak frequencies. To estimate the frequency contribution to BOLD/infraslow LFP correlation, the low frequency range was compared with the neighboring higher frequency range (indicated by a bracket, 0.2–0.3 Hz in ISO or 0.25–0.5 Hz in DMED). Examples of BOLD/infraslow LFP correlation from a representative rat for each range are shown above the coherence plot. Notably, strong BOLD/infraslow LFP correlation at the recording site was observed with the signals filtered in the low frequency ranges (< 0.1 Hz in ISO or < 0.25 Hz in DMED, indicated with brackets), but not the nearby higher frequencies (0.2–0.3 Hz in ISO or 0.25–0.5 Hz in DMED).

Fig. 4

Average coherence between BOLD and BLP. The low frequencies (A1: below ~0.1 Hz in ISO; B1: below ~0.25 in DMED) exhibited high average coherence between BOLD signals and power changes of various frequency bands of conventional LFP (BLPs). Broadband BLPs were coherent with BOLD in the ISO group, while in the DMED group, the strongest coherence was in the lower frequency bands. As a control, the time-reversed BOLD signals were used for the coherence analysis, shown in A2 and B2. A paired t-test revealed significant difference (p < 0.05) between real and sham data for the average of all bands for the peak frequencies (revealed by BOLD/infraslow LFP coherence, indicated with stars in Fig. 3, also indicated above the frequency axis with dark lines).

Fig. 5

Coherence difference between BOLD/infraslow LFP and BOLD/BLP. The differences of average BOLD coherence with infraslow LFP and with BLP of various LFP bands (indicate above the traces) are plotted for the ISO and DMED groups separately. The frequency points with a significant difference (p < 0.05, paired t-test, FDR corrected for multiple comparison) are marked with ‘*’. There are no significant differences between BOLD coherence with infraslow LFP and with BLP in ISO group; some points around 0.1–0.2 Hz in DMED group show significant coherence differences between BOLD/infra slow LFP and BOLD/BLP of the alpha band (4–8 Hz) and the gamma band (> 25 Hz).