fNIRS-EEG BCIs for Motor Rehabilitation: A Review.

Motor impairment has a profound impact on a significant number of individuals, leading to a substantial demand for rehabilitation services. Through brain-computer interfaces (BCIs), people with severe motor disabilities could have improved communication with others and control appropriately designed robotic prosthetics, so as to (at least partially) restore their motor abilities. BCI plays a pivotal role in promoting smoother communication and interactions between individuals with motor impairments and others. Moreover, they enable the direct control of assistive devices through brain signals. In particular, their most significant potential lies in the realm of motor rehabilitation, where BCIs can offer real-time feedback to assist users in their training and continuously monitor the brain's state throughout the entire rehabilitation process. Hybridization of different brain-sensing modalities, especially functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), has shown great potential in the creation of BCIs for rehabilitating the motor-impaired populations. EEG, as a well-established methodology, can be combined with fNIRS to compensate for the inherent disadvantages and achieve higher temporal and spatial resolution. This paper reviews the recent works in hybrid fNIRS-EEG BCIs for motor rehabilitation, emphasizing the methodologies that utilized motor imagery. An overview of the BCI system and its key components was introduced, followed by an introduction to various devices, strengths and weaknesses of different signal processing techniques, and applications in neuroscience and clinical contexts. The review concludes by discussing the possible challenges and opportunities for future development.

Wearable, high-density fNIRS and diffuse optical tomography technologies: a perspective.

Recent progress in optoelectronics has made wearable and high-density functional near-infrared spectroscopy (fNIRS) and diffuse optical tomography (DOT) technologies possible for the first time. These technologies have the potential to open new fields of real-world neuroscience by enabling functional neuroimaging of the human cortex at a resolution comparable to fMRI in almost any environment and population. In this perspective article, we provide a brief overview of the history and the current status of wearable high-density fNIRS and DOT approaches, discuss the greatest ongoing challenges, and provide our thoughts on the future of this remarkable technology.

Reliability and similarity of resting state functional connectivity networks imaged using wearable, high-density diffuse optical tomography in the home setting.

BACKGROUND: When characterizing the brain's resting state functional connectivity (RSFC) networks, demonstrating networks' similarity across sessions and reliability across different scan durations is essential for validating results and possibly minimizing the scanning time needed to obtain stable measures of RSFC. Recent advances in optical functional neuroimaging technologies have resulted in fully wearable devices that may serve as a complimentary tool to functional magnetic resonance imaging (fMRI) and allow for investigations of RSFC networks repeatedly and easily in non-traditional scanning environments. METHODS: Resting-state cortical hemodynamic activity was repeatedly measured in a single individual in the home environment during COVID-19 lockdown conditions using the first ever application of a 24-module (72 sources, 96 detectors) wearable high-density diffuse optical tomography (HD-DOT) system. Twelve-minute recordings of resting-state data were acquired over the pre-frontal and occipital regions in fourteen experimental sessions over three weeks. As an initial validation of the data, spatial independent component analysis was used to identify RSFC networks. Reliability and similarity scores were computed using metrics adapted from the fMRI literature. RESULTS: We observed RSFC networks over visual regions (visual peripheral, visual central networks) and higher-order association regions (control, salience and default mode network), consistent with previous fMRI literature. High similarity was observed across testing sessions and across chromophores (oxygenated and deoxygenated haemoglobin, HbO and HbR) for all functional networks, and for each network considered separately. Stable reliability values (described here as a <10% change between time windows) were obtained for HbO and HbR with differences in required scanning time observed on a network-by-network basis. DISCUSSION: Using RSFC data from a highly sampled individual, the present work demonstrates that wearable HD-DOT can be used to obtain RSFC measurements with high similarity across imaging sessions and reliability across recording durations in the home environment. Wearable HD-DOT may serve as a complimentary tool to fMRI for studying RSFC networks outside of the traditional scanning environment and in vulnerable populations for whom fMRI is not feasible.

Wearable, Integrated EEG-fNIRS Technologies: A Review.

There has been considerable interest in applying electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) simultaneously for multimodal assessment of brain function. EEG-fNIRS can provide a comprehensive picture of brain electrical and hemodynamic function and has been applied across various fields of brain science. The development of wearable, mechanically and electrically integrated EEG-fNIRS technology is a critical next step in the evolution of this field. A suitable system design could significantly increase the data/image quality, the wearability, patient/subject comfort, and capability for long-term monitoring. Here, we present a concise, yet comprehensive, review of the progress that has been made toward achieving a wearable, integrated EEG-fNIRS system. Significant marks of progress include the development of both discrete component-based and microchip-based EEG-fNIRS technologies; modular systems; miniaturized, lightweight form factors; wireless capabilities; and shared analogue-to-digital converter (ADC) architecture between fNIRS and EEG data acquisitions. In describing the attributes, advantages, and disadvantages of current technologies, this review aims to provide a roadmap toward the next generation of wearable, integrated EEG-fNIRS systems.

Time resolved speckle contrast optical spectroscopy at quasi-null source-detector separation for non-invasive measurement of microvascular blood flow.

Time (or path length) resolved speckle contrast optical spectroscopy (TD-SCOS) at quasi-null (2.85 mm) source-detector separation was developed and demonstrated. The method was illustrated by in vivo studies on the forearm muscle of an adult subject. The results have shown that selecting longer photon path lengths results in higher hyperemic blood flow change and a faster return to baseline by a factor of two after arterial cuff occlusion when compared to SCOS without time resolution. This indicates higher sensitivity to the deeper muscle tissue. In the long run, this approach may allow the use of simpler and cheaper detector arrays compared to time resolved diffuse correlation spectroscopy that are based on readily available technologies. Hence, TD-SCOS may increase the performance and decrease cost of devices for continuous non-invasive, deep tissue blood flow monitoring.

Evaluating a new generation of wearable high-density diffuse optical tomography technology via retinotopic mapping of the adult visual cortex.

Significance: High-density diffuse optical tomography (HD-DOT) has been shown to approach the resolution and localization accuracy of blood oxygen level dependent-functional magnetic resonance imaging in the adult brain by exploiting densely spaced, overlapping samples of the probed tissue volume, but the technique has to date required large and cumbersome optical fiber arrays. Aim: To evaluate a wearable HD-DOT system that provides a comparable sampling density to large, fiber-based HD-DOT systems, but with vastly improved ergonomics. Approach: We investigated the performance of this system by replicating a series of classic visual stimulation paradigms, carried out in one highly sampled participant during 15 sessions to assess imaging performance and repeatability. Results: Hemodynamic response functions and cortical activation maps replicate the results obtained with larger fiber-based systems. Our results demonstrate focal activations in both oxyhemoglobin and deoxyhemoglobin with a high degree of repeatability observed across all sessions. A comparison with a simulated low-density array explicitly demonstrates the improvements in spatial localization, resolution, repeatability, and image contrast that can be obtained with this high-density technology. Conclusions: The system offers the possibility for minimally constrained, spatially resolved functional imaging of the human brain in almost any environment and holds particular promise in enabling neuroscience applications outside of the laboratory setting. It also opens up new opportunities to investigate populations unsuited to traditional imaging technologies.

Design and validation of a mechanically flexible and ultra-lightweight high-density diffuse optical tomography system for functional neuroimaging of newborns.

Significance: Neonates are a highly vulnerable population. The risk of brain injury is greater during the first days and weeks after birth than at any other time of life. Functional neuroimaging that can be performed longitudinally and at the cot-side has the potential to improve our understanding of the evolution of multiple forms of neurological injury over the perinatal period. However, existing technologies make it very difficult to perform repeated and/or long-duration functional neuroimaging experiments at the cot-side. Aim: We aimed to create a modular, high-density diffuse optical tomography (HD-DOT) technology specifically for neonatal applications that is ultra-lightweight, low profile and provides high mechanical flexibility. We then sought to validate this technology using an anatomically accurate dynamic phantom. Approach: An advanced 10-layer rigid-flexible printed circuit board technology was adopted as the basis for the DOT modules, which allows for a compact module design that also provides the flexibility needed to conform to the curved infant scalp. Two module layouts were implemented: dual-hexagon and triple-hexagon. Using in-built board-to-board connectors, the system can be configured to provide a vast range of possible layouts. Using epoxy resin, thermochromic dyes, and MRI-derived 3D-printed moulds, we constructed an electrically switchable, anatomically accurate dynamic phantom. This phantom was used to quantify the imaging performance of our flexible, modular HD-DOT system. Results: Using one particular module configuration designed to cover the infant sensorimotor system, the device provided 36 source and 48 detector positions, and over 700 viable DOT channels per wavelength, ranging from 10 to ∼ 45 mm over an area of approximately 60 cm 2 . The total weight of this system is only 70 g. The signal changes from the dynamic phantom, while slow, closely simulated real hemodynamic response functions. Using difference images obtained from the phantom, the measured 3D localization error provided by the system at the depth of the cortex was in the of range 3 to 6 mm, and the lateral image resolution at the depth of the neonatal cortex is estimated to be as good as 10 to 12 mm. Conclusions: The HD-DOT system described is ultra-low weight, low profile, can conform to the infant scalp, and provides excellent imaging performance. It is expected that this device will make functional neuroimaging of the neonatal brain at the cot-side significantly more practical and effective.

Functional imaging of the developing brain with wearable high-density diffuse optical tomography: A new benchmark for infant neuroimaging outside the scanner environment.

Studies of cortical function in the awake infant are extremely challenging to undertake with traditional neuroimaging approaches. Partly in response to this challenge, functional near-infrared spectroscopy (fNIRS) has become increasingly common in developmental neuroscience, but has significant limitations including resolution, spatial specificity and ergonomics. In adults, high-density arrays of near-infrared sources and detectors have recently been shown to yield dramatic improvements in spatial resolution and specificity when compared to typical fNIRS approaches. However, most existing fNIRS devices only permit the acquisition of ~20-100 sparsely distributed fNIRS channels, and increasing the number of optodes presents significant mechanical challenges, particularly for infant applications. A new generation of wearable, modular, high-density diffuse optical tomography (HD-DOT) technologies has recently emerged that overcomes many of the limitations of traditional, fibre-based and low-density fNIRS measurements. Driven by the development of this new technology, we have undertaken the first study of the infant brain using wearable HD-DOT. Using a well-established social stimulus paradigm, and combining this new imaging technology with advances in cap design and spatial registration, we show that it is now possible to obtain high-quality, functional images of the infant brain with minimal constraints on either the environment or on the infant participants. Our results are consistent with prior low-density fNIRS measures based on similar paradigms, but demonstrate superior spatial localization, improved depth specificity, higher SNR and a dramatic improvement in the consistency of the responses across participants. Our data retention rates also demonstrate that this new generation of wearable technology is well tolerated by the infant population.

Dual wavelength spread-spectrum time-resolved diffuse optical instrument for the measurement of human brain functional responses.

Near-infrared spectroscopy has proven to be a valuable method to monitor tissue oxygenation and haemodynamics non-invasively and in real-time. Quantification of such parameters requires measurements of the time-of-flight of light through tissue, typically achieved using picosecond pulsed lasers, with their associated cost, complexity, and size. In this work, we present an alternative approach that employs spread-spectrum excitation to enable the development of a small, low-cost, dual-wavelength system using vertical-cavity surface-emitting lasers. Since the optimal wavelengths and drive parameters for optical spectroscopy are not served by commercially available modules as used in our previous single-wavelength demonstration platform, we detail the design of a custom instrument and demonstrate its performance in resolving haemodynamic changes in human subjects during apnoea and cognitive task experiments.

High-density speckle contrast optical tomography of cerebral blood flow response to functional stimuli in the rodent brain.

Noninvasive, three-dimensional, and longitudinal imaging of cerebral blood flow (CBF) in small animal models and ultimately in humans has implications for fundamental research and clinical applications. It enables the study of phenomena such as brain development and learning and the effects of pathologies, with a clear vision for translation to humans. Speckle contrast optical tomography (SCOT) is an emerging optical method that aims to achieve this goal by directly measuring three-dimensional blood flow maps in deep tissue with a relatively inexpensive and simple system. High-density SCOT is developed to follow CBF changes in response to somatosensory cortex stimulation. Measurements are carried out through the intact skull on the rat brain. SCOT is able to follow individual trials in each brain hemisphere, where signal averaging resulted in comparable, cortical images to those of functional magnetic resonance images in spatial extent, location, and depth. Sham stimuli are utilized to demonstrate that the observed response is indeed due to local changes in the brain induced by forepaw stimulation. In developing and demonstrating the method, algorithms and analysis methods are developed. The results pave the way for longitudinal, nondestructive imaging in preclinical rodent models that can readily be translated to the human brain.

Non-invasive and quantitative in vivo monitoring of gold nanoparticle concentration and tissue hemodynamics by hybrid optical spectroscopies.

Owing to their unique combination of chemical and physical properties, inorganic nanoparticles show a great deal of potential as suitable agents for early diagnostics and less invasive therapies. Yet, their translation to the clinic has been hindered, in part, by the lack of non-invasive methods to quantify their concentration in vivo while also assessing their effect on the tissue physiology. In this work, we demonstrate that diffuse optical techniques, employing near-infrared light, have the potential to address this need in the case of gold nanoparticles which support localized surface plasmons. An orthoxenograft mouse model of clear cell renal cell carcinoma was non-invasively assessed by diffuse reflectance and correlation spectroscopies before and over several days following a single intravenous tail vein injection of polyethylene glycol-coated gold nanorods (AuNRs-PEG). Our platform enables to resolve the kinetics of the AuNR-PEG uptake by the tumor in quantitative agreement with ex vivo inductively coupled plasma mass spectroscopy. Furthermore, it allows for the simultaneous monitoring of local tissue hemodynamics, enabling us to conclude that AuNRs-PEG do not significantly alter the animal physiology. We note that the penetration depth of this current probe was a few millimeters but can readily be extended to centimeters, hence gaining clinical relevance. This study and the methodology presented here complement the nanomedicine toolbox by providing a flexible platform, extendable to other absorbing agents that can potentially be translated to human trials.

High-resolution mapping of infraslow cortical brain activity enabled by graphene microtransistors.

Recording infraslow brain signals (<0.1 Hz) with microelectrodes is severely hampered by current microelectrode materials, primarily due to limitations resulting from voltage drift and high electrode impedance. Hence, most recording systems include high-pass filters that solve saturation issues but come hand in hand with loss of physiological and pathological information. In this work, we use flexible epicortical and intracortical arrays of graphene solution-gated field-effect transistors (gSGFETs) to map cortical spreading depression in rats and demonstrate that gSGFETs are able to record, with high fidelity, infraslow signals together with signals in the typical local field potential bandwidth. The wide recording bandwidth results from the direct field-effect coupling of the active transistor, in contrast to standard passive electrodes, as well as from the electrochemical inertness of graphene. Taking advantage of such functionality, we envision broad applications of gSGFET technology for monitoring infraslow brain activity both in research and in the clinic.

Reproducibility of parameters of postocclusive reactive hyperemia measured by diffuse optical tomography.

The application of near-infrared spectroscopy (NIRS) to assess microvascular function has shown promising results. An important limitation when using a single source-detector pair, however, is the lack of depth sensitivity. Diffuse optical tomography (DOT) overcomes this limitation using an array of sources and detectors that allow the reconstruction of volumetric hemodynamic changes. This study compares the key parameters of postocclusive reactive hyperemia measured in the forearm using standard NIRS and DOT. We show that while the mean parameter values are similar for the two techniques, DOT achieves much better reproducibility, as measured by the intraclass correlation coefficient (ICC). We show that DOT achieves high reproducibility for muscle oxygen consumption (ICC: 0.99), time to maximal HbO2 (ICC: 0.94), maximal HbO2 (ICC: 0.99), and time to maximal HbT (ICC: 0.99). Absolute reproducibility as measured by the standard error of measurement is consistently smaller and close to zero (ideal value) across all parameters measured by DOT compared to NIRS. We conclude that DOT provides a more robust characterization of the reactive hyperemic response and show how the availability of volumetric hemodynamic changes allows the identification of areas of temporal consistency, which could help characterize more precisely the microvasculature.

Reduced-order modeling of light transport in tissue for real-time monitoring of brain hemodynamics using diffuse optical tomography.

This paper proposes a new reconstruction method for diffuse optical tomography using reduced-order models of light transport in tissue. The models, which directly map optical tissue parameters to optical flux measurements at the detector locations, are derived based on data generated by numerical simulation of a reference model. The reconstruction algorithm based on the reduced-order models is a few orders of magnitude faster than the one based on a finite element approximation on a fine mesh incorporating a priori anatomical information acquired by magnetic resonance imaging. We demonstrate the accuracy and speed of the approach using a phantom experiment and through numerical simulation of brain activation in a rat's head. The applicability of the approach for real-time monitoring of brain hemodynamics is demonstrated through a hypercapnic experiment. We show that our results agree with the expected physiological changes and with results of a similar experimental study. However, by using our approach, a three-dimensional tomographic reconstruction can be performed in ∼3 s per time point instead of the 1 to 2 h it takes when using the conventional finite element modeling approach.