There is a growing interest in the possibility of using functional neuroimaging techniques to aid in detecting covert awareness in patients who are thought to be suffering from a disorder of consciousness. Immerging optical techniques such as time-resolved functional near-infrared spectroscopy (TR-fNIRS) are ideal for such applications due to their low-cost, portability, and enhanced sensitivity to brain activity. The aim of this case study was to investigate for the first time the ability of TR-fNIRS to detect command driven motor imagery (MI) activity in a functionally locked-in patient suffering from Guillain–Barré syndrome. In addition, the utility of using TR-fNIRS as a brain–computer interface (BCI) was also assessed by instructing the patient to perform an MI task as affirmation to three questions: (1) confirming his last name, (2) if he was in pain, and (3) if he felt safe. At the time of this study, the patient had regained limited eye movement, which provided an opportunity to accurately validate a BCI after the fNIRS study was completed. Comparing the two sets of responses showed that fNIRS provided the correct answers to all of the questions. These promising results demonstrate for the first time the potential of using an MI paradigm in combination with fNIRS to communicate with functionally locked-in patients without the need for prior training.

This article introduces the second part of the Neurophotonics Special Section on Functional Near Infrared Spectroscopy.

Understanding how cortical networks interact in response to task demands is important both for providing insight into the brain’s processing architecture and for managing neurological diseases and mental disorders. High-density diffuse optical tomography (HD-DOT) is a neuroimaging technique that offers the significant advantages of having a naturalistic, acoustically controllable environment and being compatible with metal implants, neither of which is possible with functional magnetic resonance imaging. We used HD-DOT to study the effective connectivity and assess the modulatory effects of speech intelligibility and syntactic complexity on functional connections within the cortical speech network. To accomplish this, we extend the use of a generalized psychophysiological interaction (PPI) analysis framework. In particular, we apply PPI methods to event-related HD-DOT recordings of cortical oxyhemoglobin activity during auditory sentence processing. We evaluate multiple approaches for selecting cortical regions of interest and for modeling interactions among these regions. Our results show that using subject-based regions has minimal effect on group-level connectivity maps. We also demonstrate that incorporating an interaction model based on estimated neural activity results in significantly stronger effective connectivity. Taken together our findings support the use of HD-DOT with PPI methods for noninvasively studying task-related modulations of functional connectivity.

Safe locomotion is a crucial aspect of human daily living that requires well-functioning motor control processes. The human neuromotor control of daily activities such as walking relies on the complex interaction of subcortical and cortical areas. Technical developments in neuroimaging systems allow the quantification of cortical activation during the execution of motor tasks. Functional near-infrared spectroscopy (fNIRS) seems to be a promising tool to monitor motor control processes in cortical areas in freely moving subjects. However, so far, there is no established standardized protocol regarding the application and data processing of fNIRS signals that limits the comparability among studies. Hence, this systematic review aimed to summarize the current knowledge about application and data processing in fNIRS studies dealing with walking or postural tasks. Fifty-six articles of an initial yield of 1420 publications were reviewed and information about methodology, data processing, and findings were extracted. Based on our results, we outline the recommendations with respect to the design and data processing of fNIRS studies. Future perspectives of measuring fNIRS signals in movement science are discussed.

Regular physical exercise has been shown to benefit neurocognitive functions, especially enhancing neurogenesis in the hippocampus. However, the effects of a single exercise session on cognitive functions are controversial. To address this issue, we measured hemodynamic changes in the brain during physical exercise using near-infrared spectroscopy (NIRS) and investigated related effects on memory consolidation processes. Healthy young participants underwent two experimental visits. During each visit, they performed an associative memory task in which they first encoded a series of pictures, then spent 30-min exercising or resting, and finally were asked to recall the picture associations. We used NIRS to track changes in oxygenated hemoglobin concentration over the prefrontal cortex during exercise and rest. To characterize local tissue oxygenation and perfusion, we focused on low frequency oscillations in NIRS, also called vasomotion. We report a significant increase in associative memory consolidation after exercise, as compared to after rest, along with an overall increase in vasomotion. Additionally, performance improvement after exercise correlated positively with power in the neurogenic component (0.02 to 0.04 Hz) and negatively with power in the endothelial component (0.003 to 0.02 Hz). Overall, these results suggest that changes in vasomotion over the prefrontal cortex during exercise may promote memory consolidation processes.

Transcranial magnetic stimulation (TMS) is a noninvasive method used to excite or inhibit cortical activity for experimental, diagnostic, and therapeutic interventions. However, nonmotor regions of the brain targeted in TMS therapies, such as the dorsolateral prefrontal cortex (DLPFC), offer no extrinsic response to stimulation, resulting in a need for a practical method for the evaluation of treatment. We sought to determine the capability of a continuous-wave light emitting diodes (LED)-based functional near-infrared spectroscopy (fNIRS) system to measure evoked cortical hemoglobin changes in the DLPFC during the simultaneous application of TMS to the left-DLPFC under brief stimulation paradigms used in the clinic. Seventeen healthy participants received short TMS trains at F3 in four different stimulation conditions (single pulse, high frequency, intermittent theta burst, and sham) while adjacent fNIRS measurements were recorded. Ten 2-s trains of each stimulation type were delivered with an intertrial interval of 40 s. Results indicated that high-frequency stimulation produces a larger and more evident response than other measured conditions. These findings show that a continuous-wave LED-based fNIRS system can be used to measure TMS-evoked responses and that future TMS applications can benefit from concurrent assessment of localized cortical activation changes.

Occupational noise frequently occurs in the work environment in military intelligence, surveillance, and reconnaissance operations. This impacts cognitive performance by acting as a stressor, potentially interfering with the analysts’ decision-making process. We investigated the effects of different noise stimuli on analysts’ performance and workload in anomaly detection by simulating a noisy work environment. We utilized functional near-infrared spectroscopy (fNIRS) to quantify oxy-hemoglobin (HbO) and deoxy-hemoglobin concentration changes in the prefrontal cortex (PFC), as well as behavioral measures, which include eye tracking, reaction time, and accuracy rate. We hypothesized that noisy environments would have a negative effect on the participant in terms of anomaly detection performance due to the increase in workload, which would be reflected by an increase in PFC activity. We found that HbO for some of the channels analyzed were significantly different across noise types (p<0.05). Our results also indicated that HbO activation for short-intermittent noise stimuli was greater in the PFC compared to long-intermittent noises. These approaches using fNIRS in conjunction with an understanding of the impact on human analysts in anomaly detection could potentially lead to better performance by optimizing work environments.

Functional near-infrared spectroscopy (fNIRS) has been proposed as an affordable, fast, and robust alternative to many neuroimaging modalities yet it still has long way to go to be adapted in the clinic. One request from the clinicians has been the delivery of a simple and straightforward metric (a so-called biomarker) from the vast amount of data a multichannel fNIRS system provides. We propose a simple-straightforward signal processing algorithm derived from fNIRS-HbO2 data collected during a modified version of the color-word matching Stroop task that consists of three different conditions. The algorithm starts with a wavelet-transform-based preprocessing, then uses partial correlation analysis to compute the functional connectivity matrices at each condition and then computes the global efficiency values. To this end, a continuous wave 16 channels fNIRS device (ARGES Cerebro, Hemosoft Inc., Turkey) was used to measure the changes in HbO2 concentrations from 12 healthy volunteers. We have considered 10% of strongest connections in each network. A strong Stroop interference effect was found between the incongruent against neutral condition (p=0.01) while a similar significance was observed for the global efficiency values decreased from neutral to congruent to incongruent conditions [F(2,33)=3.46, p=0.043]. The findings bring us closer to delivering a biomarker derived from fNIRS data that can be reliably and easily adopted by the clinicians.

Anesthesia monitoring currently needs a reliable method to evaluate the effects of the anesthetics on its primary target, the brain. This study focuses on investigating the clinical usability of a functional near-infrared spectroscopy (fNIRS)-derived machine learning classifier to perform automated and real-time classification of maintenance and emergence states during sevoflurane anesthesia. For 19 surgical procedures, we examine the entire continuum of the maintenance–transition–emergence phases and evaluate the predictive capability of a support vector machine (SVM) classifier during these phases. We demonstrate the robustness of the predictions made by the SVM classifier and compare its performance with that of minimum alveolar concentration (MAC) and bispectral (BIS) index-based predictions. The fNIRS-SVM investigated in this study provides evidence to the usability of the fNIRS signal for anesthesia monitoring. The method presented enables classification of the signal as maintenance or emergence automatically as well as in real-time with high accuracy, sensitivity, and specificity. The features local mean HbTotal, std HbO2, local min Hb and HbO2, and range Hb and HbO2 were found to be robust biomarkers of this binary classification task. Furthermore, fNIRS-SVM was capable of identifying emergence before movement in a larger number of patients than BIS and MAC.

Functional near-infrared spectroscopy (fNIRS) offers an advantage over traditional functional imaging methods [such as functional magnetic resonance imaging (fMRI)] by allowing participants to move and speak relatively freely. However, neuroimaging while actively speaking has proven to be particularly challenging due to the systemic artifacts that tend to be located in the critical brain areas. To overcome these limitations and enhance the utility of fNIRS, we describe methods for investigating cortical activity during spoken language tasks through refinement of deoxyhemoglobin (deoxyHb) signals with principal component analysis (PCA) spatial filtering to remove global components. We studied overt picture naming and compared oxyhemoglobin (oxyHb) and deoxyHb signals with and without global component removal using general linear model approaches. Activity in Broca’s region and supplementary motor cortex was observed only when the filter was applied to the deoxyHb signal and was shown to be spatially comparable to fMRI data acquired using a similar task and to meta-analysis data. oxyHb signals did not yield expected activity in Broca’s region with or without global component removal. This study demonstrates the utility of a PCA spatial filter on the deoxyHb signal in revealing neural activity related to a spoken language task and extends applications of fNIRS to natural and ecologically valid conditions.

Extracorporeal membrane oxygenation (ECMO) is a life-supporting therapy for critically ill patients with severe respiratory and/or cardiovascular failure. Cerebrovascular impairment can result in hemorrhagic and ischemic complications commonly seen in the patients supported on ECMO. We investigated the degree of cerebral autoregulation impairment during ECMO as well as whether it is predictive of neuroimaging abnormalities. Spontaneous fluctuations of mean arterial pressure (MAP) and cerebral tissue oxygen saturation (SctO2) were continuously measured during the ECMO run. The dynamic relationship between the MAP and SctO2 fluctuations was assessed based on wavelet transform coherence (WTC). Neuroimaging was conducted during and/or after ECMO as standard of care, and the abnormalities were evaluated based on a scoring system that had been previously validated among ECMO patients. Of the 25 patients, 8 (32%) had normal neuroimaging, 7 (28%) had mild to moderate neuroimaging abnormalities, and the other 10 (40%) had severe neuroimaging abnormalities. The degrees of cerebral autoregulation impairment quantified based on WTC showed significant correlations with the neuroimaging scores (R=0.66; p<0.0001). Evidence that cerebral autoregulation impairment during ECMO was related to the patients’ neurological outcomes was provided.

Multimodal monitoring has become particularly common in the study of human brain function. In this context, combined, synchronous measurements of functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) are getting increased interest. Because of the absence of electro-optical interference, it is quite simple to integrate these two noninvasive recording procedures of brain activity. fNIRS and EEG are both scalp-located procedures. fNIRS estimates brain hemodynamic fluctuations relying on spectroscopic measurements, whereas EEG captures the macroscopic temporal dynamics of brain electrical activity through passive voltages evaluations. The “orthogonal” neurophysiological information provided by the two technologies and the increasing interest in the neurovascular coupling phenomenon further encourage their integration. This review provides, together with an introduction regarding the principles and future directions of the two technologies, an evaluation of major clinical and nonclinical applications of this flexible, low-cost combination of neuroimaging modalities. fNIRS–EEG systems exploit the ability of the two technologies to be conducted in an environment or experimental setting and/or on subjects that are generally not suited for other neuroimaging modalities, such as functional magnetic resonance imaging, positron emission tomography, and magnetoencephalography. fNIRS–EEG brain monitoring settles itself as a useful multimodal tool for brain electrical and hemodynamic activity investigation.

With the aim of transitioning functional near-infrared spectroscopy (fNIRS) technology from the laboratory environment to everyday applications, the field has seen a recent push toward the development of wearable/miniaturized, multiwavelength, multidistance, and modular instruments. However, it is challenging to unite all these requirements in a precision instrument with low noise, low drift, and fast sampling characteristics. We present the concept and development of a wearable fNIRS instrument that combines all these key features with the goal of reliably and accurately capturing brain hemodynamics. The proposed instrument consists of a modular network of miniaturized optode modules that include a four-wavelength light source and a highly sensitive silicon photomultiplier detector. Simultaneous measurements with short-separation (7.5 mm; containing predominantly extracerebral signals) and long-separation (20 mm or more; containing both extracerebral and cerebral information) channels are used with short-channel regression filtering methods to increase robustness of fNIRS measurements. Performance of the instrument was characterized with phantom measurements and further validated in human in vivo measurements, demonstrating the good raw signal quality (signal-to-noise ratio of 64 dB for short channels; robust measurements up to 50 mm; dynamic optical range larger than 160 dB), the valid estimation of concentration changes (oxy- and deoxyhemoglobin, and cytochrome-c-oxidase) in muscle and brain, and the detection of task-evoked brain activity. The results of our preliminary tests suggest that the presented fNIRS instrument outperforms existing instruments in many aspects and bears high potential for real-time single-trial fNIRS applications as required for wearable brain–computer interfaces.

By exploiting a multichannel portable instrument for time-domain near-infrared spectroscopy (TD-NIRS), we characterized healthy neonates’ brains in term of optical properties and hemodynamic parameters. In particular, we assessed the absolute values of the absorption and reduced scattering coefficients at two wavelengths, together with oxy-, deoxy- and total hemoglobin concentrations, and the blood oxygen saturation of the neonates’ brains. In this study, 33 healthy full-term neonates were tested, obtaining the following median values: 0.28 and 0.31  cm−1 for μa at 690 and 820 nm, respectively; 5.8 and 5.3  cm−1 for μs′ at 690 and 820 nm, respectively; 103  μM for cO2Hb; 42.6  μM for cHHb; 146  μM for ctHb; 72% for sO2. In general, the agreement of these values with the sparse existing literature appears not always consistent. These findings demonstrate the first measurements of optical properties of the healthy neonate brain using TD-NIRS and show the need for clarification of optical properties across methods and populations.

This editorial introduces the Special issue from SPIE Brain 2017.

An automated massive histology setup combined with an optical coherence tomography (OCT) microscope was used to image a total of n=5 whole mouse brains. Each acquisition generated a dataset of thousands of OCT volumetric tiles at a sampling resolution of 4.9×4.9×6.5  μm. This paper describes techniques for reconstruction and segmentation of the sliced brains. In addition to the measured OCT optical reflectivity, a single scattering photon model was used to compute the attenuation coefficients within each tissue slice. Average mouse brain templates were generated for both the OCT reflectivity and attenuation contrasts and were used with an n-tissue segmentation algorithm. To better understand the brain tissue OCT contrast origin, one of the mouse brains was acquired using dMRI and coregistered to its corresponding assembled brain. Our results indicate that the optical reflectivity in a fiber bundle varies with its orientation, its fiber density, and the number of fiber orientations it contains. The OCT mouse brain template generation and coregistration to dMRI data demonstrate the potential of this massive histology technique to pursue cross-sectional, multimodal, and multisubject investigations of small animal brains.

As the optogenetic field expands, the need for precise targeting of neocortical circuits only grows more crucial. This work demonstrates a technique for using Solidworks® computer-aided design (CAD) and readily available stereotactic brain atlases to create a three-dimensional (3-D) model of the dorsal region of area visual cortex 4 (V4D) of the macaque monkey (Macaca fascicularis) visual cortex. The 3-D CAD model of the brain was used to customize an 8×6 Utah optrode array (UOA) after it was determined that a high-density (13×13) UOA caused extensive damage to marmoset (Callithrix jacchus) primary visual cortex as assessed by electrophysiological recording of spiking activity through a 1.5-mm-diameter through glass via. The 8×6 UOA was customized for optrode length (400  μm), optrode width (≤100  μm), optrode pitch (400  μm), backplane thickness (500  μm), and overall form factor (3.45  mm×2.65  mm). Two 8×6 UOAs were inserted into layer VI of macaque V4D cortices with minimal damage as assessed in fixed tissue cytochrome oxidase staining in nonrecoverable surgeries. Additionally, two 8×6 arrays were implanted in mice (Mus musculus) motor cortices, providing early evidence for long-term tolerability (over 6 months), and for the ability to integrate the UOA with a Holobundle light delivery system toward patterned optogenetic stimulation of cortical networks.

Alterations to cerebral blood flow (CBF) have been implicated in diverse neurological conditions. Near-infrared spectroscopy (NIRS)-measured regional cerebral tissue oxygen saturation (rSO2) provides an estimate of oxygenation of interrogated cerebral volume useful in identifying variations in oxygen supply to cerebral tissue and in monitoring cerebrovascular function. CO2-inhalation-based hypercapnic breathing challenges were used to simulate CBF dysregulation, utilizing NIRS to monitor the CBF autoregulatory response. A breathing circuit was designed to administer CO2-compressed air mixtures and assess CBF regulatory responses to hypercapnia in 26 healthy young adults. One to three hypercapnic challenges of 5 or 10 min duration were delivered to each subject while continuously monitoring rSO2, partial pressure of end tidal CO2 (PETCO2), and vital signs. Change in rSO2 (ΔrSO2) during CO2 inhalation positively correlated to ΔPETCO2 (R2=0.40). Grouping subjects into three exercise factor levels (h/week), (1) 0, (2) <0 and <10, and (3) <10 showed significantly greater ΔrSO2 responses to CO2 challenges for level 3 subjects but similar PETCO2 responses for the three groups. Exercising greater than 10 h/week may produce a higher resting cerebrovascular reactivity (CVR) to CO2 inhalation. Establishing baseline values of rSO2 and CVR to CO2 may aid in early detection of CBF changes.

Turbo-Satori is a neurofeedback and brain–computer interface (BCI) toolbox for real-time functional near-infrared spectroscopy (fNIRS). It incorporates multiple pipelines from real-time preprocessing and analysis to neurofeedback and BCI applications. The toolbox is designed with a focus in usability, enabling a fast setup and execution of real-time experiments. Turbo-Satori uses an incremental recursive least-squares procedure for real-time general linear model calculation and support vector machine classifiers for advanced BCI applications. It communicates directly with common NIRx fNIRS hardware and was tested extensively ensuring that the calculations can be performed in real time without a significant change in calculation times for all sampling intervals during ongoing experiments of up to 6 h of recording. Enabling immediate access to advanced processing features also allows the use of this toolbox for students and nonexperts in the field of fNIRS data acquisition and processing. Flexible network interfaces allow third party stimulus applications to access the processed data and calculated statistics in real time so that this information can be easily incorporated in neurofeedback or BCI presentations.

Retinal degenerative diseases, such as retinitis pigmentosa (RP) and dry age-related macular degeneration, have led to loss of vision in millions of individuals. Currently, no surgical or medical treatment is available, although optogenetic therapies are in clinical development. We demonstrate vision restoration using multicharacteristics opsin (MCO1) in animal models with degenerated retina. MCO1 is reliably delivered to specific retinal cells via intravitreal injection of adeno-associated virus (vMCO1), leading to significant improvement in visually guided behavior conducted using a radial arm water maze. The time to reach the platform and the number of error arms decreased significantly after delivery of MCO1. Notably, the improvement in visually guided behavior was observed even at light intensity levels orders of magnitude lower than that required for channelrhodopsin-2 opsin. Viability of vMCO1-treated retina is not compromised by chronic light exposure. Safe virus-mediated MCO1 delivery has potential for effective gene therapy of diverse retinal degenerations in patients.

The use of optogenetics to activate or inhibit neurons is an important toolbox for neuroscientists. Several optogenetic devices are in use. These range from wired systems where the optoprobe is physically connected to the light source by a tether, to wireless systems that are remotely controlled. There are advantages and disadvantages of both; the wired systems are lightweight but limit movement due to the tether, and wireless systems allow unrestricted movement but may be heavier than wired systems. Both systems can be expensive to install and use. We have developed a low cost, wireless optogenetic probe, CerebraLux, built from off-the-shelf components. CerebraLux consists of two separable units; an optical component consisting of the baseplate holding the fiber-optic in place and an electronic component consisting of a light-emitting diode, custom-printed circuit board, an infrared receiver, microcontroller, and a rechargeable, lightweight lithium polymer battery. The optical component (0.5 g) is mounted on the head permanently, whereas the electronic component (2.3 g) is removable and is applied for each experiment. We describe the device, provide all designs and specifications, the methods to manufacture and use the device in vivo, and demonstrate feasibility in a mouse behavioral paradigm.

Cathodal-transcranial direct current stimulation induces therapeutic effects in animal ischemia models by preventing the expansion of ischemic injury during the hyperacute phase of ischemia. However, its efficacy is limited by an accompanying decrease in cerebral blood flow. On the other hand, peripheral sensory stimulation can increase blood flow to specific brain areas resulting in rescue of neurovascular functions from ischemic damage. Therefore, the two modalities appear to complement each other to form an integrated treatment modality. Our results showed that hemodynamics was improved in a photothrombotic ischemia model, as cerebral blood volume and hemoglobin oxygen saturation (SO2) recovered to 71% and 76% of the baseline values, respectively. Furthermore, neural activities, including somatosensory-evoked potentials (110% increase), the alpha-to-delta ratio (27% increase), and the (delta+theta)/(alpha+beta) ratio (27% decrease), were also restored. Infarct volume was reduced by 50% with a 2-fold preservation in the number of neurons and a 6-fold reduction in the number of active microglia in the infarct region compared with the untreated group. Grip strength was also better preserved (28% higher) compared with the untreated group. Overall, this nonpharmacological, nonintrusive approach could be prospectively developed into a clinical treatment modality.

Near-infrared spectroscopy-mediated neurofeedback (NIRS-NFB) is a promising therapeutic intervention for patients with neurological diseases. Studies have shown that NIRS-NFB can facilitate task-related cortical activation and induce task-specific behavioral changes. These findings indicate that the effect of neuromodulation depends on local cortical function. However, when the target cortical region has multiple functions, our understanding of the effects is less clear. This is true in the supplementary motor area (SMA), which is involved both in postural control and upper-limb movement. To address this issue, we investigated the facilitatory effect of NIRS SMA neurofeedback on cortical activity and behavior, without any specific task. Twenty healthy individuals participated in real and sham neurofeedback. Balance and hand dexterity were assessed before and after each NIRS-NFB session. We found a significant interaction between assessment periods (pre/post) and condition (real/sham) with respect to balance as assessed by the center of the pressure path length but not for hand dexterity as assessed by the 9-hole peg test. SMA activity only increased during real neurofeedback. Our findings indicate that NIRS-NFB itself has the potential to modulate focal cortical activation, and we suggest that it be considered a therapy to facilitate the SMA for patients with postural impairment.

Alterations of cellular bioenergetics are a common feature in most neurodegenerative disorders. However, there is a selective vulnerability of different brain regions, cell types, and even mitochondrial populations to these metabolic disturbances. Thus, the aim of our study was to establish and validate an in vivo metabolic imaging technique to screen for mitochondrial function on the subcellular level. Based on nicotinamide adenine dinucleotide (phosphate) fluorescence lifetime imaging microscopy [NAD(P)H FLIM], we performed a quantitative correlation to high-resolution respirometry. Thereby, we revealed mitochondrial matrix pH as a decisive factor in imaging NAD(P)H redox state. By combining both parameters, we illustrate a quantitative, high-resolution assessment of mitochondrial function in metabolically modified cells as well as in an amyloid precursor protein-overexpressing model of Alzheimer’s disease. Our metabolic imaging technique provides the basis for dissecting mitochondrial deficits not only in a range of neurodegenerative diseases, shedding light onto bioenergetic failures of cells remaining in their metabolic microenvironment.

There is not yet a comprehensive view of how the color of light affects the cerebral and systemic physiology in humans. The aim was to address this deficit through basic research. Since cerebral and systemic physiological parameters are likely to interact, it was necessary to establish an approach, which we have termed “systemic-physiology-augmented functional near-infrared spectroscopy (SPA-fNIRS) neuroimaging.” This multimodal approach measures the systemic and cerebral physiological response to exposure to light of different colors. In 14 healthy subjects (9 men, 5 women, age: 33.4±10.5 years, range: 24 to 57 years) exposed to red, green, and blue light (10-min intermittent wide-field visual color stimulation; 15×20  s blocks of visual stimulation), brain hemodynamics and oxygenation were measured by fNIRS on the prefrontal cortex (PFC) and visual cortex (VC) simultaneously, in addition with systemic parameters. This study demonstrated that (i) all colors elicited responses in the VC, whereas only blue evoked a response in the PFC; (ii) there was a color-dependent effect on cardiorespiratory activity; (iii) there was significant change in neurosystemic functional connectivity; (iv) cerebral hemodynamic responses in the PFC and changes in the cardiovascular system were gender and age dependent; and (v) electrodermal activity and psychological state showed no stimulus-evoked changes, and there was no dependence on color of light, age, and gender. We showed that short-term light exposure caused color-dependent responses in cerebral hemodynamics/oxygenation as well as cardiorespiratory dynamics. Additionally, we showed that neurosystemic functional connectivity changes even during apparently stress-free tasks—an important consideration when using any of the hemodynamic neuroimaging methods (e.g. functional magnetic resonance imaging, positron emission tomography, and fNIRS). Our findings are important for future basic research and clinical applications as well as being relevant for everyday life.

Neural activity is an important biomarker for the presence of neurodegenerative diseases, cerebrovascular alterations, and brain trauma; furthermore, it is a surrogate marker for treatment effects. These pathologies may occur and evolve in a long time-period, thus, noninvasive, transcutaneous techniques are necessary to allow a longitudinal follow-up. In the present work, we have customized noninvasive, transcutaneous, diffuse correlation spectroscopy (DCS) to localize changes in cerebral blood flow (CBF) induced by neural activity. We were able to detect changes in CBF in the somatosensory cortex by using a model of electrical forepaw stimulation in rats. The suitability of DCS measurements for longitudinal monitoring was demonstrated by performing multiple sessions with the same animals at different ages (from 6 to 18 months). In addition, functional DCS has been cross-validated by comparison with functional magnetic resonance imaging (fMRI) in the same animals in a subset of the time-points. The overall results obtained with transcutaneous DCS demonstrates that it can be utilized in longitudinal studies safely and reproducibly to locate changes in CBF induced by neural activity in the small animal brain.

Following acute traumatic brain injury (TBI), timely transport to a hospital can significantly improve the prognosis for recovery. There is, however, a dearth of quantitative biomarkers for brain injury that can be rapidly acquired and interpreted in active, field environments in which TBIs are frequently incurred. We explored potential functional indicators for TBI that can be noninvasively obtained through portable detection modalities, namely optical and electrophysiological approaches. By combining diffuse correlation spectroscopy with colocalized electrophysiological measurements in a mouse model of TBI, we observed concomitant alterations in sensory-evoked cerebral blood flow (CBF) and electrical potentials following controlled cortical impact. Injury acutely reduced the peak amplitude of both electrophysiological and CBF responses, which mostly recovered to baseline values within 30 min, and intertrial variability for these parameters was also acutely altered. Notably, the postinjury dynamics of the CBF overshoot and undershoot amplitudes differed significantly; whereas the amplitude of the initial peak of stimulus-evoked CBF recovered relatively rapidly, the ensuing undershoot did not appear to recover within 30 min of injury. Additionally, acute injury induced apparent low-frequency oscillatory behavior in CBF ( &lt;1  Hz). Histological assessment indicated that these physiological alterations were not associated with any major, persisting anatomical changes. Several time-domain features of the blood flow and electrophysiological responses showed strong correlations in recovery kinetics. Overall, our results reveal an array of stereotyped, injury-induced alterations in electrophysiological and hemodynamic responses that can be rapidly obtained using a combination of portable detection techniques.

Quantifying rapidly varying perturbations in cerebral tissue absorption and scattering can potentially help to characterize changes in brain function caused by ischemic trauma. We have developed a platform for rapid intrinsic signal brain optical imaging using macroscopically structured light. The device performs fast, multispectral, spatial frequency domain imaging (SFDI), detecting backscattered light from three-phase binary square-wave projected patterns, which have a much higher refresh rate than sinusoidal patterns used in conventional SFDI. Although not as fast as “single-snapshot” spatial frequency methods that do not require three-phase projection, square-wave patterns allow accurate image demodulation in applications such as small animal imaging where the limited field of view does not allow single-phase demodulation. By using 655, 730, and 850 nm light-emitting diodes, two spatial frequencies ( fx=0 and 0.3  mm−1), three spatial phases (120 deg, 240 deg, and 360 deg), and an overall camera acquisition rate of 167 Hz, we map changes in tissue absorption and reduced scattering parameters ( μa and μs′) and oxy- and deoxyhemoglobin concentration at ∼14  Hz. We apply this method to a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) to quantify hemodynamics and scattering on temporal scales ( Δt) ranging from tens of milliseconds to minutes. We observe rapid concurrent spatiotemporal changes in tissue oxygenation and scattering during CA and following CPR, even when the cerebral electrical signal is absent. We conclude that square-wave SFDI provides an effective technical strategy for assessing cortical optical and physiological properties by balancing competing performance demands for fast signal acquisition, small fields of view, and quantitative information content.

This note explains a publication error involving the original paper.