Evidence for the importance of measuring total brain activity in neuroimaging

Abstract

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 (N o ) 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 + N o )-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 there may be inherent neuronal 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...

Glutamatergic Function in the Resting Awake Human Brain is Supported by Uniformly High Oxidative Energy

“…The magnitude of neuronal signaling in the human brain, and by inference the commensurate energy demand, underscores the functional relevance of resting activity and has profound implications for interpreting fMRI experiments in humans. [12][13][14] Given the rapidly increasing use of resting-state fMRI in mapping networks-defined as a subset of cortical and subcortical gray-matter regions that function together 15,16 -it is important to quantitatively establish if in the resting human the metabolic demand for neuronal signaling is high, as has been established for the rodent, 5,[7][8][9] and to what extent metabolic demand varies across gray-matter regions. 13 C magnetic resonance spectroscopy (MRS) of 13 C-labeled substrates (e.g., glucose and acetate) can measure rates of 13 C label incorporation into cell-specific pools (e.g., glutamate and gamino butyric acid (GABA) are predominantly neuronal and glutamine is predominantly glial) thereby estimating metabolic fluxes 17 of neuronal glucose oxidation (CMR glc(ox),N ) and of total glutamate neurotransmitter cycling (V cyc(tot) ).…”

Quantitative fMRI and oxidative neuroenergetics

“…While recent experimental evidence is changing the opinion that spontaneous neuronal activity is simply “noise” (for recent reviews see (Hyder and Rothman, 2011; Northoff et al, 2010; Ringach, 2009; Shulman et al, 2007)), it should be noted that classical studies had raised the importance of spontaneous activity for understanding brain function (Adrian, 1941). Future studies need considerations about properties of the stimulus (e.g., amplitude, contrast, etc.)…”

Poststimulus undershoots in cerebral blood flow and BOLD fMRI responses are modulated by poststimulus neuronal activity

“…The optimal definition of a baseline signal in BOLD data is not straightforward because the brain is never truly at rest (31,32). Here we calculate the mean baseline value for each subject from the average signal in the 24-to 30-s time period, and use this value to convert all single trials to percent signal change.…”