A BOLD window into brain waves

The brain is never inactive. Neurons fire at leisurely rates most of the time, even in sleep (1), although occasionally they fire more intensely, for example, when presented with certain stimuli. Coordinated changes in the activity and excitability of many neurons underlie spontaneous fluctuations in the electroencephalogram (EEG), first observed almost a century ago. These fluctuations can be very slow (infraslow oscillations, <0.1 Hz; slow oscillations, <1 Hz; and slow waves or delta waves, 1–4 Hz), intermediate (theta, 4–8 Hz; alpha, 8–12 Hz; and beta, 13–20 Hz), and fast (gamma, >30 Hz). Moreover, slower fluctuations appear to group and modulate faster ones (1, 2). The BOLD signal underlying functional magnetic resonance imaging (fMRI) also exhibits spontaneous fluctuations at the timescale of tens of seconds (infraslow, <0.1 Hz), which occurs at all times, during task-performance as well as during quiet wakefulness, rapid eye movement (REM) sleep, and non-REM sleep (NREM). Although the precise mechanism underlying the BOLD signal is still being investigated (3–5), it is becoming clear that spontaneous BOLD fluctuations are not just noise, but are tied to fluctuations in neural activity. In this issue of PNAS, He et al. (6) have been able to directly investigate the relationship between BOLD fluctuations and fluctuations in the brain's electrical activity in human subjects. He et al. (6) took advantage of the seminal observation by Biswal et al. (7) that spontaneous BOLD fluctuations in regions belonging to the same functional system are strongly correlated. As expected, He et al. saw that fMRI BOLD fluctuations were strongly correlated among regions within the sensorimotor system, but much less between sensorimotor regions and control regions (nonsensorimotor). The twist was that they did the fMRI recordings in subjects who had been implanted with intracranial electrocorticographic (ECoG) electrodes to record regional EEG signals (to localize epileptic foci). In a separate session, He et al. examined correlations in EEG signals between different regions. They found that, just like the BOLD fluctuations, infraslow and slow fluctuations in the EEG signal from sensorimotor-sensorimotor pairs of electrodes were positively correlated, whereas signals from sensorimotor-control pairs were not. Moreover, the correlation persisted across arousal states: in waking, NREM, and REM sleep. Finally, using several statistical approaches, they found a remarkable correspondence between regional correlations in the infraslow BOLD signal and regional correlations in the infraslow-slow EEG signal (