The amount of information acquired with functional neuroimaging techniques, particularly fNIRS and fMRI, is rapidly growing and has enormous potential for studying human brain functioning. Therefore, many scientists focus on solving computational neuroimaging and Big Data issues to advance the discipline. However, the main obstacle—the accurate translation of the hemodynamic response (HR) by the investigation of a physiological phenomenon called neurovascular coupling—is still not fully overcome and, more importantly, often overlooked in this context. This article provides a brief and critical overview of significant findings from cellular biology and in vivo brain physiology with a focus on advancing existing HR modelling paradigms. A brief historical timeline of these disciplines of neuroscience is presented for readers to grasp the concept better, and some possible solutions for further scientific discussion are provided.

This study investigated the potential role of sex and handedness on the performance of a computerised Wisconsin Card Sorting Test (WCST) in healthy participants by applying functional near-infrared spectroscopy (fNIRS). We demonstrated significant (p < 0.05) sex-related differences of hemodynamic response in the prefrontal cortex of 70 healthy participants (female, n = 35 and male, n = 35; right-handed, n = 40 and left-handed, n = 30). In contrast, behavioural results of the WCST do not show sex bias, which is consistent with previous literature. Because of this, we compared ours and sparse previous fNIRS studies on the WCST. We propose that, according to recent studies of neurovascular coupling, this contradiction between neuroimaging and behavioural results may be explained by normal variability in neurovascular dynamics.