Significance: The reliability of functional near-infrared spectroscopy (fNIRS) measurements is reduced by systemic physiology. Short-channel regression algorithms aim at removing systemic “noise” by subtracting the signal measured at a short source–detector separation (mainly scalp hemodynamics) from the one of a long separation (brain and scalp hemodynamics). In literature, incongruent approaches on the selection of the optimal regressor signal are reported based on different assumptions on scalp hemodynamics properties.

Aim: We investigated the spatial and temporal distribution of scalp hemodynamics over the sensorimotor cortex and evaluated its influence on the effectiveness of short-channel regressions.

Approach: We performed hand-grasping and resting-state experiments with five subjects, measuring with 16 optodes over sensorimotor areas, including eight 8-mm channels. We performed detailed correlation analyses of scalp hemodynamics and evaluated 180 hand-grasping and 270 simulated (overlaid on resting-state measurements) trials. Five short-channel regressor combinations were implemented with general linear models. Three were chosen according to literature, and two were proposed based on additional physiological assumptions [considering multiple short channels and their Mayer wave (MW) oscillations].

Results: We found heterogeneous hemodynamics in the scalp, coming on top of a global close-to-homogeneous behavior (correlation 0.69 to 0.92). The results further demonstrate that short-channel regression always improves brain activity estimates but that better results are obtained when heterogeneity is assumed. In particular, we highlight that short-channel regression is more effective when combining multiple scalp regressors and when MWs are additionally included.

Conclusion: We shed light on the selection of optimal regressor signals for improving the removal of systemic physiological artifacts in fNIRS. We conclude that short-channel regression is most effective when assuming heterogeneous hemodynamics, in particular when combining spatial- and frequency-specific information. A better understanding of scalp hemodynamics and more effective short-channel regression will promote more accurate assessments of functional brain activity in clinical and research settings.