Investigation of functional near-infrared spectroscopy signal quality and development of the hemodynamic phase correlation signal

Abstract. Significance: There is a longstanding recommendation within the field of fNIRS to use oxygenated (HbO2) and deoxygenated (HHb) hemoglobin when analyzing and interpreting results. Despite this, many fNIRS studies do focus on HbO2 only. Previous work has shown that HbO2 on its own is susceptible to systemic interference and results may mostly reflect that rather than functional activation. Studies using both HbO2 and HHb to draw their conclusions do so with varying methods and can lead to discrepancies between studies. The combination of HbO2 and HHb has been recommended as a method to utilize both signals in analysis. Aim: We present the development of the hemodynamic phase correlation (HPC) signal to combine HbO2 and HHb as recommended to utilize both signals in the analysis. We use synthetic and experimental data to evaluate how the HPC and current signals used for fNIRS analysis compare. Approach: About 18 synthetic datasets were formed using resting-state fNIRS data acquired from 16 channels over the frontal lobe. To simulate fNIRS data for a block-design task, we superimposed a synthetic task-related hemodynamic response to the resting state data. This data was used to develop an HPC-general linear model (GLM) framework. Experiments were conducted to investigate the performance of each signal at different SNR and to investigate the effect of false positives on the data. Performance was based on each signal’s mean T-value across channels. Experimental data recorded from 128 participants across 134 channels during a finger-tapping task were used to investigate the performance of multiple signals [HbO2, HHb, HbT, HbD, correlation-based signal improvement (CBSI), and HPC] on real data. Signal performance was evaluated on its ability to localize activation to a specific region of interest. Results: Results from varying the SNR show that the HPC signal has the highest performance for high SNRs. The CBSI performed the best for medium-low SNR. The next analysis evaluated how false positives affect the signals. The analyses evaluating the effect of false positives showed that the HPC and CBSI signals reflect the effect of false positives on HbO2 and HHb. The analysis of real experimental data revealed that the HPC and HHb signals provide localization to the primary motor cortex with the highest accuracy. Conclusions: We developed a new hemodynamic signal (HPC) with the potential to overcome the current limitations of using HbO2 and HHb separately. Our results suggest that the HPC signal provides comparable accuracy to HHb to localize functional activation while at the same time being more robust against false positives.


Comparison of virtual reality and hands on activities in science education via fNIRS
Lamb, R 2018 HbO2 The relationship between the superior frontal cortex and alpha oscillation in a flanker task: Simultaneous recording of EEG and NIRS Suzuki, K 2018 Other Negative affect is related to reduced differential neural responses to social and non-social stimuli in 5-to-8 month old infants: A fNIRS study Van Der Kant, A 2018 HbO2 and HbR Cooperation makes two less-creative individuals turn into a highly-creative pair Xue, H 2018 HbO2 Brain-to-brain synchrony in parent child dyads and the relationship with emotion regulation revealed by fNIRS-based hyperscanning Reindl, V 2018 HbO2 Interpersonal brain synchronization associated with working alliance during psychological counselling Zhang, Y 2018 HbO2 A transferable high-intensity intermittent exercise improves executive performance in association with dorsolateral prefrontal activation in young adults Kujach, S 2018

HbO2 and HbR
Neural basis for reduced executive performance with hypoxic exercise Ochi, G 2018 HbO2 Eye contact modulates facial mimicry in 4-month-old infants: An EMG and fNIRS study de Klerk, CCJM 2018 HbO2 and HbR Changes in cerebral activation in individuals with and without visual vertigo during optic flow: A fNIRS study Hoppes, C 2018 HbO2 Relationship between sensorimotor cortical activation as assessed fNIRS and lower extremity motor coordination in bilateral cerebral palsy Sukal-Moulton, T 2018 HbT Meditation and the brain -Neuronal correlates of mindfulness as assessed with NIRS Gundel, F 2018 HbR Inter-brain synchrony in mother-child dyads during cooperation: An fNIRS hyperscanning study Miller, J 2019 HbO2 Brain activation and adaption of deception processing during dyadic face-to-face interaction Tang The effects of CACNA1C gene polymorphism on prefrontal cortex in both schizophrenia patients and healthy controls Zhang, Z 2019

HbO2 and HbR
Changes of functional response in sensorimotor cortex of preterm and full-term infants during the first year: An fNIRS study Rosa de Oliveira, S 2019

HbO2 and HbR
The role of the right prerontal cortex in recognition of facial expressions in depressed individuals: fNIRS study Mannelis, A 2019 HbR English spoken word segmentation activates the prefrontal cortex and temporo-parietal junction in Chinese ESL learners: A fNIRS study Li, Y 2020 HbO2 Infant brain responses to live face-to-face interaction with their mothers: Combining fNIRS with a modified still-face paradigm Behrendt, H F 2020 HbO2 So young, yet so mature? Electrophysiological and vascular correlates of phonotactic processing in 18-month-olds Steber, S 2020 HbO2 and HbR Evaluation of neurocognitive function of prefrontal cortex in ornithine transcarbamylase deficiency Anderson, A 2020 CBSI Behavioral and brain synchronization differences between expert and novice teachers when collaborating with students Sun, B 2020 HbO2 Linguistic and non-linguistic non-adjacent dependency learning in early development Van Der Kant, A 2020 HbO2 and HbR The influence of maternal anxiety and depression symptoms on fNIRS brain responses to emotional faces in 5-and 7-month-old infants Porto, J A 2020 HbO2 Cortical activity measured by functional near infrared spectroscopy during a theory of mind task in subjects with schizophrenia, bipolar disorder and healthy controls Sayar-Akaslan, D HbO2 and HbR Similar activation patterns in the prefrontal cortex for Chinese and Japanese verbal fluency tests with syllable cues as revealed by near-infrared spectroscopy Song, M 2020 HbO2 Neural correlates of mindful emotion regulation in high and low ruminators Rosenbaum, D 2020 CBSI Increased prefrontal oxygenation prior to and at the onset of over-ground locomotion in humans Matsukawa, K 2020 HbO2 Hemodynamic and behavioral peculiarities in response to emotional stimuli in children with attention deficit hyperactivity disorder: An fNIRS study Mauri, M 2020 HbO2 and HbR Neural alignment during face-to-face spontaneous deception: Does gender make a difference?
Chen, M 2020 HbO2 Which obstacle attributes place additional demands on higher-level cognitive function in patients with Parkinson's disease?
Sharon, T 2020 CBSI Dyad sex composition effect on inter-brain synchronization in face-to-face cooperation Li, Y 2020 HbO2 Different strategies, distinguished cooperation efficiency, and brain synchronization for couples: An fNIRS-based hyperscanning study Tang, Y 2020 HbO2 Exhaustion disorder and altered brain activity in frontal cortex detected with fNIRS Skau, S 2020 HbO2 and HbR Self-other overlap and interpersonal neural synchronization serially mediate the effect of behavioral synchronization on prosociality Feng, X 2020 HbO2 Functional near-infrared spectroscopy (fNIRS) as a tool to assist the diagnosis of major psychiatric disorders in a Chinese population Wei, Y 2020 HbO2 and HbR Social exclusion influences conditioned fear acquisition and generalization: A mediating effect from the medial prefrontal cortex Dou, H 2020 HbO2 Uncovering electrophysiological and vascular signatures of implicit emotional prosody Steber, S 2020

HbO2 and HbR
The "gift effect" on functional brain connectivity. Inter-brain synchronization when prosocial behavior is in action Balconi, M 2020

HbO2 and HbR
The Brain Differentially Prepares Inner and Overt Speech Production: Electrophysiological and Vascular Evidence Stephan, F 2020 HbO2 and HbR Developmental Differences in Cortical Activation During Action Observation, Action Execution and Interpersonal Synchrony: An fNIRS Study Su, WC 2020 HbO2 The averaged inter-brain coherence between the audience and a violinist predicts the popularity of violin performanc Hou, Y 2020 HbO2 Instructor-learner brain coupling discriminates between instructional approaches and predicts learning Pan, Y 2020 CBSI Functional lateralization of arithmetic processing in the intraparietal sulcus is associated with handedness Artemenko, C 2020 CBSI Affiliative bonding between teachers and students through interpersonal synchronisation in brain activity Zheng, L 2020 HbO2

Effects of Tai Chi Chuan on Inhibitory Control in Elderly Women: An fNIRS Study
Yang, Y 2020 HbO2 How the Brain Understands Spoken and Sung Sentences Rossi, S 2020 HbO2 and HbR Stimulus modality influences the acquisition and use of the rule-based strategy and the similarity-based strategy in category learning Wu, J 2020 Not Stated Fixed and flexible: Dynamic prefrontal activations and working memory capacity relationships vary with memory demand Shah, A M 2020 HbO2 Autism Symptoms Modulate Interpersonal Neural Synchronization in Children with Autism Spectrum Disorder in Cooperative Interactions Wang, Q 2020 HbO2

Table S4
List of papers reviewed to determine signal usage.

Channel Configurations
Figure S11 Hitachi Channel Configuration. Used to acquire resting state fNIRS data for the formation of synthetic data.

Figure S12
Shimadzu LABNIRS Channel Configuration. Used to acquire data from finger tapping experiment.  Table S5 MNI coordinates of channels and corresponding anatomical locations for Shimadzu Configuration.

Figure S13
Method of detecting HbO2 and HHb reversal pattern. Example output for typical and reversed data is shown. The red and blue shaded regions refer to the positive and negative areas of the Z-scored HbDiff signal.
N1 Synthetic data to test the reversal pattern identification method was generated by reversing the polarity of HbO2 and HHb of the task-related HRF for three random task blocks in each dataset for the high SNR signal (see Fig. 2 in the main text). We then tested the method with a ratio threshold of 1, which included more non-reversed blocks. Lowering this to 0.5 was able to improve the specificity of the method.

Figure S14
Raw beta values obtained from the synthetic analysis. The top panel is from the SNR test, the middle panel is the result from reversing the HHb signal, and the bottom is reversing the HbO2 signal.