Investigation of the Pattern of the Hemodynamic Response as Measured by Functional Near-Infrared Spectroscopy (fNIRS) Studies in Newborns, Less Than a Month Old: A Systematic Review

Abstract

It has been 20 years since functional near-infrared spectroscopy (fNIRS) was first used to investigate the evoked hemodynamic response to a stimulus in newborns. The hemodynamic response to functional activation is well-established in adults, with an observed increase in concentration change of oxygenated hemoglobin (Δ[HbO2]) and decrease in deoxygenated hemoglobin (Δ[HHb]). However, functional studies in newborns have revealed a mixed response, particularly with Δ[HHb] where an inconsistent change in direction is observed. The reason for this heterogeneity is unknown, with potential explanations arising from differing physiology in the developing brain, or differences in instrumentation or methodology. The aim of this review is to collate the findings from studies that have employed fNIRS to monitor cerebral hemodynamics in term newborn infants aged 1 day−1 month. A total of 46 eligible studies were identified; some studies investigated more than one stimulus type, resulting in a total of 51 reported results. The NIRS parameters reported varied across studies with 50/51 cases reporting Δ[HbO2], 39/51 reporting Δ[HHb], and 13/51 reporting total hemoglobin concentration Δ[HbT] (Δ[HbO2] + Δ[HHb]). However, of the 39 cases reporting Δ[HHb] in graphs or tables, only 24 studies explicitly discussed the response (i.e., direction of change) of this variable. In the studies where the fNIRS responses were discussed, 46/51 cases observed an increase in Δ[HbO2], 7/51 observed an increase or varied Δ[HHb], and 2/51 reported a varied or negative Δ[HbT]. An increase in Δ[HbO2] and decrease or no change in Δ[HHb] was observed in 15 studies. By reviewing this body of literature, we have identified that the majority of research articles reported an increase in Δ[HbO2] across various functional tasks and did not report the response of Δ[HHb]. Confirming the normal, healthy hemodynamic response in newborns will allow identification of unhealthy patterns and their association to normal neurodevelopment.

Cerebral hemodynamic responses in preterm-born neonates to visual stimulation: classification according to subgroups and analysis of frontotemporal–occipital functional connectivity

“…46 In a recently published review investigating the pattern of the HR in fNIRS studies in term newborns less than 1 month old, the authors came to the conclusion that the typical response in newborns is not well established. 2 The majority of papers identified for this review reported an increase in Δ½O 2 Hb, with only some of them reporting a decrease in Δ½HHb. Furthermore, they did not observe a clear association between the reported response and stimulus type.…”

“…Neuroimaging with fNIRS has the potential to provide insights into the origin of neonatal brain lesions, as well as into functional development of both the normal and the abnormal brain. 2,3 The ability of fNIRS to access neurovascular coupling associated with neuronal activity offers a useful opportunity to investigate, for example, the neural basis of visual cognitive development in infants. This is of special interest in preterm-born infants, as many of them develop visual cognitive impairment in later childhood.…”

“…12 Neuroimaging with fNIRS has been shown to be a practical and powerful tool to examine the status of hemodynamic physiology in infants as well as in adults. 2,13,14 Neuronal activity is associated with changes in tissue metabolism (neurometabolic coupling) and tissue hemodynamics (neurovascular coupling). These changes lead in turn to characteristic changes in the oxygenated (oxyhemoglobin, O 2 Hb) and deoxygenated (deoxyhemoglobin, HHb) states of hemoglobin: a distinct increase in the concentration in [O 2 Hb] and a slight decrease in [HHb].…”

“…[18][19][20] However, the development of the HRF pattern in the human brain remained unclear; some fNIRS studies reported an inverted HRF pattern (i.e., a decrease in blood flow or [O 2 Hb]) in young infants in response to perceptual stimuli, whereas some studies did not. 2,21,22 This has been a controversial issue, and investigations about this aspect in preterm-born neonates are particularly sparse, partly because the investigation of HRFs of these neonates using fNIRS is a relatively new subject. [22][23][24] Notably, a recent fNIRS study 23 reported developmental changes in phase differences of spontaneous low-frequency oscillations of [O 2 Hb] and [HHb] in pretermborn infants.…”

A Mini-Review on Functional Near-Infrared Spectroscopy (fNIRS): Where Do We Stand, and Where Should We Go?

“…Aasted [40] Statistical analysis of fNIRS data 2014 Tak [41] Pattern of hemodynamic response in newborn < 1 month 2018 de Roever [42] Pattern of hemodynamic response in infants 2018 Issard [43] Integration of fNIRS with: The advantages and disadvantages of fNIRS have been widely reported in several recent review articles [5,47,48]. Unlike other neuroimaging modalities, fNIRS has a very high experimental flexibility.…”