Modelling confounding effects from extracerebral contamination and systemic factors on functional near-infrared spectroscopy

Haemodynamics-based neuroimaging is widely used to study brain function. Regional blood flow changes characteristic of neurovascular coupling provide an important marker of neuronal activation. However, changes in systemic physiological parameters such as blood pressure and concentration of CO2 can also affect regional blood flow and may confound haemodynamics-based neuroimaging. Measurements with functional near-infrared spectroscopy (fNIRS) may additionally be confounded by blood flow and oxygenation changes in extracerebral tissue layers. Here we investigate these confounds using an extended version of an existing computational model of cerebral physiology, 'BrainSignals'. Our results show that confounding from systemic physiological factors is able to produce misleading haemodynamic responses in both positive and negative directions. By applying the model to data from previous fNIRS studies, we demonstrate that such potentially deceptive responses can indeed occur in at least some experimental scenarios. It is therefore important to record the major potential confounders in the course of fNIRS experiments. Our model may then allow the observed behaviour to be attributed among the potential causes and hence reduce identification errors

Investigating the effects of systemic physiology on Functional Near-Infrared Spectroscopy based resting-state functional connectivity networks

The use of neuroimaging has enhanced our understanding of the human brain and its associated functions. Research and development of these neuroimaging techniques have made it possible to study the brain in both healthy and patient populations, including neurological and psychiatric conditions (Pinti et al., 2020). The present thesis aims to contribute to the research and development of neuroimaging techniques by improving the functional near-infrared spectroscopy (fNIRS) technology. The objective of this thesis is to improve the research application of fNIRS-based resting state functional connectivity (rsFC) studies and enhance the clinical relevance of fNIRS

Systematic investigation of changes in oxidized cerebral cytochrome c oxidase concentration during frontal lobe activation in healthy adults

Using transcranial near-infrared spectroscopy (NIRS) to measure changes in the redox state of cerebral cytochrome c oxidase (Δ[oxCCO]) during functional activation in healthy adults is hampered by instrumentation and algorithm issues. This study reports the Δ[oxCCO] response measured in such a setting and investigates possible confounders of this measurement. Continuous frontal lobe NIRS measurements were collected from 11 healthy volunteers during a 6-minute anagram-solving task, using a hybrid optical spectrometer (pHOS) that combines multi-distance frequency and broadband components. Only data sets showing a hemodynamic response consistent with functional activation were interrogated for a Δ[oxCCO] response. Simultaneous systemic monitoring data were also available. Possible influences on the Δ[oxCCO] response were systematically investigated and there was no effect of: 1) wavelength range chosen for fitting the measured attenuation spectra; 2) constant or measured, with the pHOS in real-time, differential pathlength factor; 3) systemic hemodynamic changes during functional activation; 4) changes in optical scattering during functional activation. The Δ[oxCCO] response measured in the presence of functional activation was heterogeneous, with the majority of subjects showing significant increase in oxidation, but others having a decrease. We conclude that the heterogeneity in the Δ[oxCCO] response is physiological and not induced by confounding factors in the measurements. © 2012 Optical Society of America

Best practices for fNIRS publications

The application of functional near-infrared spectroscopy (fNIRS) in the neurosciences has been expanding over the last 40 years. Today, it is addressing a wide range of applications within different populations and utilizes a great variety of experimental paradigms. With the rapid growth and the diversification of research methods, some inconsistencies are appearing in the way in which methods are presented, which can make the interpretation and replication of studies unnecessarily challenging. The Society for Functional Near-Infrared Spectroscopy has thus been motivated to organize a representative (but not exhaustive) group of leaders in the field to build a consensus on the best practices for describing the methods utilized in fNIRS studies. Our paper has been designed to provide guidelines to help enhance the reliability, repeatability, and traceability of reported fNIRS studies and encourage best practices throughout the community. A checklist is provided to guide authors in the preparation of their manuscripts and to assist reviewers when evaluating fNIRS papers

Systemic physiology augmented functional near-infrared spectroscopy: a powerful approach to study the embodied human brain.

In this Outlook paper, we explain why an accurate physiological interpretation of functional near-infrared spectroscopy (fNIRS) neuroimaging signals is facilitated when systemic physiological activity (e.g., cardiorespiratory and autonomic activity) is measured simultaneously by employing systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). The rationale for SPA-fNIRS is twofold: (i) SPA-fNIRS enables a more complete interpretation and understanding of the fNIRS signals measured at the head since they contain components originating from neurovascular coupling and from systemic physiological sources. The systemic physiology signals measured with SPA-fNIRS can be used for regressing out physiological confounding components in fNIRS signals. Misinterpretations can thus be minimized. (ii) SPA-fNIRS enables to study the embodied brain by linking the brain with the physiological state of the entire body, allowing novel insights into their complex interplay. We envisage the SPA-fNIRS approach will become increasingly important in the future

Frequency-domain analysis of fNIRS fluctuations induced by rhythmic mental arithmetic

Functional near-infrared spectroscopy (fNIRS) is an increasingly used technology for imaging neural correlates of cognitive processes. However, fNIRS signals are commonly impaired by task-evoked and spontaneous hemodynamic oscillations of non-cerebral origin, a major challenge in fNIRS research. In an attempt to isolate the task-evoked cortical response, we investigated the coupling between hemodynamic changes arising from superficial and deep layers during mental effort. For this aim, we applied a rhythmic mental arithmetic task to induce cyclic hemodynamic fluctuations suitable for effective frequency-resolved measurements. Twenty university students aged 18–25 years (eight males) underwent the task while hemodynamic changes were monitored in the forehead using a newly developed NIRS device, capable of multi-channel and multi-distance recordings. We found significant task-related fluctuations for oxy-and deoxy-hemoglobin, highly coherent across shallow and deep tissue layers, corroborating the strong influence of surface hemodynamics on deep fNIRS signals. Importantly, after removing such surface contamination by linear regression, we show that the frontopolar cortex response to a mental math task follows an unusual inverse oxygenation pattern. We confirm this finding by applying for the first time an alternative method to estimate the neural signal, based on transfer function analysis and phasor algebra. Altogether, our results demonstrate the feasibility of using a rhythmic mental task to impose an oscillatory state useful to separate true brain functional responses from those of non-cerebral origin. This separation appears to be essential for a better understanding of fNIRS data and to assess more precisely the dynamics of the neuro-visceral link

Effects of Systemic Physiology on Mapping Resting-State Networks Using Functional Near-Infrared Spectroscopy

Resting-state functional connectivity (rsFC) has gained popularity mainly due to its simplicity and potential for providing insights into various brain disorders. In this vein, functional near-infrared spectroscopy (fNIRS) is an attractive choice due to its portability, flexibility, and low cost, allowing for bedside imaging of brain function. While promising, fNIRS suffers from non-neural signal contaminations (i.e., systemic physiological noise), which can increase correlation across fNIRS channels, leading to spurious rsFC networks. In the present work, we hypothesized that additional measurements with short channels, heart rate, mean arterial pressure, and end-tidal CO2 could provide a better understanding of the effects of systemic physiology on fNIRS-based resting-state networks. To test our hypothesis, we acquired 12 min of resting-state data from 10 healthy participants. Unlike previous studies, we investigated the efficacy of different pre-processing approaches in extracting resting-state networks. Our results are in agreement with previous studies and reinforce the fact that systemic physiology can overestimate rsFC. We expanded on previous work by showing that removal of systemic physiology decreases intra- and inter-subject variability, increasing the ability to detect neural changes in rsFC across groups and over longitudinal studies. Our results show that by removing systemic physiology, fNIRS can reproduce resting-state networks often reported with functional magnetic resonance imaging (fMRI). Finally, the present work details the effects of systemic physiology and outlines how to remove (or at least ameliorate) their contributions to fNIRS signals acquired at rest

Optical imaging and spectroscopy for the study of the human brain: status report

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions

Optical imaging and spectroscopy for the study of the human brain: status report.

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions