When a person performs different tasks such as movement or is stimulated visually, neurons in different regions of the cortex are activated. This functional activation requires energy and thus increases cerebral blood flow locally to replenish glucose and oxygen supply in the activated region. Neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS), use this interplay to infer spatial and temporal characteristics of neuronal activity based on measurable hemodynamic parameters. However, the brain works even at rest. Evidence of this activity has been found by careful analysis of spontaneous fluctuations of hemodynamic signals during the resting state (i.e., a state without any task or stimulation). More important, high-level activities have been observed in functionally related regions (e.g., analogous regions in the brain hemispheres) for a given activated region—a demonstration of functional connectivity. Clinical studies using fMRI have already demonstrated that resting-state functional connectivity is either weak or aberrant in various brain disorders, thus providing an emerging analysis tool to be used by clinicians.

While significant advances have been made with fMRI on this subject, NIRS can contribute to further understanding resting-state connectivity by providing high temporal resolution (~100 ms) and direct hemodynamic parameters and by targeting different populations hard to assess with other techniques, such as infants. By use of diffusing light, NIRS and tomography can probe oxyhemoglobin and deoxyhemoglobin concentrations through the skull, down to the cortex for adults and whole brain for neonates. Ultimately, NIRS with resting-state connectivity analysis may be able to give feedback to clinicians to optimally manage and treat patients with critical brain injuries or disorders.

The first applications of near-infrared technique to connectivity studies focused on using diffuse optical tomography with dense light source and detector arrangements covering motor and visual cortices. In particular, motor or visual tasks were performed to identify the region of interest (i.e., seed) for the resting-state connectivity analysis. In this manuscript, Mesquita et al. extend this emerging research method by arranging light sources and detectors into a combination of 50 pairs that allowed them to cover the whole head. By using 3.0 cm as a default distance between each source and detector, they could investigate interconnection among multiple cortical regions in frontal, temporal, parietal, and occipital lobes. The authors used resting-state-only protocol on healthy adult brains to record fluctuations of hemodynamic parameters and blood pressure as auxiliary parameter simultaneously. Although systemic contribution, such as cardiac, respiratory, and blood pressure frequencies, to the optical signal are a concern when spontaneous fluctuations are isolated, the authors show that NIRS can be utilized to reliably estimate connectivity by filtering out their contributions (especially blood pressure) with a stationary filter regression method. By choosing a source–detector pair as a seed, they computed the correlation values between the time-courses of the seed with all the other pairs and projected them onto a topographic map. They found that regions with similar functionalities are correlated, in agreement with previous literature. Seeds in the sensorimotor and visual cortices showed stronger bilateral correlations with the symmetric pair than the prefrontal region. For the group of 11 subjects, total hemoglobin concentration (i.e., the sum of oxyhemoglobin and deoxyhemoglobin concentrations) seems to exhibit the most robust correlation maps and better localization of connectivity patterns among hemodynamic parameters, similar to what has been found in (task-oriented) functional experiments with NIRS. In general, this comprehensive study establishes a baseline for resting-state functional connectivity between different regions in the healthy adult human brain. This baseline serves as a springboard for future translational clinical study involving neonate or diseased populations unable to perform functional tasks.

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