Evidence for the importance of measuring total brain activity in neuroimaging.

A principal goal in neuroscience is to understand how neuronal populations across different brain regions process information from the vibrant world, rich in moment-to-moment variations of sight, smell, sound, touch, etc. Traditional inquiries examine how the evoked neuronal responses differ with stimuli (e.g., sound or touch). However, the brain detects stimuli reliably even when ambient (or background) conditions shift owing to external (e.g., light vs. dark) and/or internal (e.g., alert vs. sleepy) factors. Recent investigations have assessed whether evoked neuronal activity (ΔN) varies when the brain’s operational (or baseline) state is altered, whereby including an independent measure of baseline (or spontaneous) neuronal activity (No) provides a total measure of neuronal activity for the perturbed state (N). In PNAS, Li et al. (1) demonstrate in the rat’s olfactory bulb that total bulbar activity level reached upon odor exposure (i.e., N = ΔN + No)—measured by extracellular recordings—is independent of the bulb’s baseline activity level. This result agrees well with previous observations from other cortical sensory systems, using a variety of neuroimaging techniques [e.g., functional MRI (fMRI), optical imaging, and electrophysiology (2–9)]. Taken together, these studies (1– 9) imply that theremaybe inherentneuronal mechanisms to ensure a similar level of information transfer from sensory input, regardless of external/internal situations that may impact the brain’s baseline state (10). Li et al. (1) measured odor-induced bulbar activity under different baseline states. Whereas spontaneous neuronal activity in the two baseline states (achieved by varying anesthetic doses) differed by approximately twofold, nearly identical levels of total neuronal activity were reached upon the same odor exposure from each baseline state. This phenomenon was observed regardless of which bulbar layer (mitral, granular) the recordings were obtained from, the type of anesthetic (pentobarbital, chloral hydrate) that was used to achieve the baseline state, and the type (aldehyde, ketone, ester) and concentration (up to fivefold difference) of the odor that was exposed to the rat. Previous optical imaging and fMRI studies examined odor-induced bulbar activity patterns and how topologies and intensities vary with concentration (11, 12). For a given odor the topology of the bulbar activity pattern is largely independent of concentration, but the intensity of bulbar activity correlates positively with concentration. Because these studies were conducted with only one baseline state, results from Li et al. (1) extend the previous findings regarding the neuronal encoding of quality (with pattern topology) and concentration of odor (with pattern intensity) across different baseline states. If the baseline state variation studies of the olfactory bulb (1) are combined with similar studies of the olfactory cortex (13), we may deduce that, regardless of the baseline state, maintaining high-fidelity transmission of smell signals—from the olfactory epithelium, through the olfactory bulb, to the olfactory cortex—could be a system-level phenomenon. Indeed, numerous laboratories (1–9) using a variety of neuroimaging techniques (e.g., fMRI, optical imaging, electrophysiology), studying dissimilar primary sensory systems (e.g., somatosensory cortex, visual cortex, olfactory bulb), across various species (e.g., rat, cat, monkey, human), and under diverse experimental conditions (e.g., awake and anesthetized with volatile and nonvolatile agents) observe that the total neuronal activity reached upon stimulation is, to a first order, independent of the spontaneous (i.e., nonevoked) baseline state neuronal activity (10).