Previous research has demonstrated changes in neurovascular activation of the prefrontal cortex to increased working memory load. The primary purpose of the current paper was to investigate overload of working memory capacity using functional near-infrared spectroscopy (fNIRS) within the framework of motivational intensity theory. A secondary goal was to explore the influence of the correlation-based signal improvement (CBSI) as a method for correcting the influence of systemic variables. In study one, 30 participants (15 female, mean age = 21.09 years, s.d. = 2.9 years) performed a verbal version of the n-back working memory task under four levels of demand (easy, hard, very hard, and impossible). In contrast to the raw data, CBSI-transformed fNIRS data indicated that neurovascular coupling was highest at hard demand when the task was challenging but success was possible. The second study (N  =  30; 15 female, mean age = 22.4 years, s.d. = 5.3) replicated the working memory manipulation with the addition of low versus high levels of financial reward. Analyses of CBSI-transformed levels of oxygenated (HbO) and deoxygenated (HHb) hemoglobin replicated the first study at right lateral regions of the prefrontal cortex (BA46). HHb_CBSI data were significantly reduced at impossible demand for participants receiving the higher level of financial reward. The study is the first to support predictions from the motivational intensity model using neurovascular data. In addition, the application of CBSI to fNIRS data was found to improve the sensitivity of HbO and Hbb to the independent variables.

We implemented a wide field-of-view visible-light optical coherence microscope (OCM) for investigating ex-vivo brain tissue of patients diagnosed with Alzheimer’s disease (AD) and of a mouse model of AD. A submicrometer axial resolution in tissue was achieved using a broad visible light spectrum. The use of various objective lenses enabled reaching micrometer transversal resolution and the acquisition of images of microscopic brain features, such as cell structures, vessels, and white matter tracts. Amyloid-beta plaques in the range of 10 to 70  μm were visualized. Large field-of-view images of young and old mouse brain sections were imaged using an automated x  −  y  −  z stage. The plaque load was characterized, revealing an age-related increase. Human brain tissue affected by cerebral amyloid angiopathy was investigated and hyperscattering structures resembling amyloid beta accumulations in the vessel walls were identified. All results were in good agreement with histology. A comparison of plaque features in both human and mouse brain tissue was performed, revealing an increase in plaque load and a decrease in reflectivity for mouse as compared with human brain tissue. Based on the promising outcome of our experiments, visible light OCM might be a powerful tool for investigating microscopic features in ex-vivo brain tissue.

We present a dual-modality imaging system combining laser speckle contrast imaging and oxygen-dependent quenching of phosphorescence to simultaneously map cortical blood flow and oxygen tension (pO2) in mice. Phosphorescence signal localization is achieved through the use of a digital micromirror device (DMD) that allows for selective excitation of arbitrary regions of interest. By targeting both excitation maxima of the oxygen-sensitive Oxyphor PtG4, we are able to examine the effects of excitation wavelength on the measured phosphorescence lifetime. We demonstrate the ability to measure the differences in pO2 between arteries and veins and large changes during a hyperoxic challenge. We dynamically monitor blood flow and pO2 during DMD-targeted photothrombotic occlusion of an arteriole and highlight the presence of an ischemia-induced depolarization. Chronic tracking of the ischemic lesion over eight days revealed a rapid recovery, with the targeted vessel fully reperfusing and pO2 returning to baseline values within five days. This system has broad applications for studying the acute and chronic pathophysiology of ischemic stroke and other vascular diseases of the brain.

A good understanding of age-dependent changes and modifications in brain networks is crucial for fully exploring the effects of aging on the human brain. Few reports have been found in studies of functional brain networks using functional near-infrared spectroscopy (fNIRS). Moreover, little is known about the feasibility of using fNIRS to assess age-related changes in brain connectomes. This study applied whole brain fNIRS measurement, combined with graph theory analysis, to assess the age-dependent changes in resting-state brain networks. Five to eight minutes of resting-state brain hemodynamic signals were recorded from 48 participants (18 young adults and 30 older adults) with 133 optical channels covering the majority of the cortical regions. Both local and global graph metrics were computed to identify the age-related changes of topographical brain networks. Older adults showed an overall decline of both global and local efficiency compared to young adults, as well as the decline of small-worldness. In addition, young adults showed the abundance of hubs in the prefrontal cortex, whereas older adults revealed the hub shifts to the sensorimotor cortex. These obvious shifts of hubs may potentially indicate decreases of the decision-making, memory, and other high-order functions as people age. Our results showed consistent findings with published literature and also demonstrated the feasibility of whole-head fNIRS measurements to assess age-dependent changes in resting-state brain networks.

Coherent Raman fiber probes have not yet found their way into the clinic despite their immense potential for label-free sensing and imaging. This is mainly due to the traditional bulky laser systems required to create the high peak power laser pulses needed for coherent Raman, as well as the complications that arise from the propagation of this type of energy through silica. Specifically, a coherent anti-Stokes Raman scattering (CARS) probe that could select its integration volume at high resolution, away from the tip of the fiber, is particularly interesting in the case of electrode implantation neurosurgeries, wherein it is possible to place optical fibers on-board the chronic electrode and provide optical guidance during its implantation, through the semi-transparent tip. To this clinical end, we have created an all fiber CARS system, consisting of small, rapidly tunable, turn-key fiber-lasers, capable of creating high wavenumber CARS spectra on the order of tens-of-milliseconds. The use of traditional silica fibers is made possible by the use of the laser’s long pulse-widths (25 ps). The probe itself has an outer diameter of 250  μm allowing it to fit within commercially available metal tubes that can replace deep brain stimulation (DBS) stylets. Using this system, we identified brain tissue types in intact nonhuman primates’ brains and showed the ability to delineate white and gray matters with high resolution. Its advantages over spontaneous Raman stem from the orders of magnitude improvement in spatial resolution, its inherent translatability to three-dimensional (3-D) imaging, as well as the theoretical ability to remove parasitic Raman signal from probe encasements, such as a DBS electrode. The system is planned to have clinical implications in neurosurgical guidance as well as diseased tissue detection.

Though optical imaging of human brain function is gaining momentum, widespread adoption is restricted in part by a tradeoff among cap wearability, field of view, and resolution. To increase coverage while maintaining functional magnetic resonance imaging (fMRI)-comparable image quality, optical systems require more fibers. However, these modifications drastically reduce the wearability of the imaging cap. The primary obstacle to optimizing wearability is cap weight, which is largely determined by fiber diameter. Smaller fibers collect less light and lead to challenges in obtaining adequate signal-to-noise ratio. Here, we report on a design that leverages the exquisite sensitivity of scientific CMOS cameras to use fibers with ∼30  ×   smaller cross-sectional area than current high-density diffuse optical tomography (HD-DOT) systems. This superpixel sCMOS DOT (SP-DOT) system uses 200-μm-diameter fibers that facilitate a lightweight, wearable cap. We developed a superpixel algorithm with pixel binning and electronic noise subtraction to provide high dynamic range (>105), high frame rate (>6  Hz), and a low effective detectivity threshold (∼200  fW  /  Hz1/2-mm2), each comparable with previous HD-DOT systems. To assess system performance, we present retinotopic mapping of the visual cortex (n  =  5 subjects). SP-DOT offers a practical solution to providing a wearable, large field-of-view, and high-resolution optical neuroimaging system.

Recently, a variety of tissue optical clearing techniques have been developed to reduce light scattering for imaging deeper and three-dimensional reconstruction of tissue structures. Combined with optical imaging techniques and diverse labeling methods, these clearing methods have significantly promoted the development of neuroscience. Each of them has its own characteristics with certain advantages and disadvantages. Though there are some comparison results, the clearing methods covered are limited and the evaluation indices lack uniformity, which made it difficult to select a best-fit protocol from numerous methods for clearing in practical applications. Hence, it is necessary to systematically assess and compare these clearing methods. We evaluated the performance of seven typical clearing methods, including 3-D imaging of solvent-cleared organs (3DISCO), ultimate DISCO (uDISCO), see deep brain (SeeDB), ScaleS, ClearT2, clear, unobstructed brain imaging cocktails and computational analysis, and passive CLARITY technique (PACT), on mouse brain samples. First, we compared the clearing effect and clearing time as well as size deformation on brain tissues. Further, we evaluated the fluorescence preservation and the increase of imaging depth induced by different methods. The results showed that 3DISCO, uDISCO, and PACT possessed excellent clearing capability on mouse brains, ScaleS and SeeDB rendered moderate transparency, whereas ClearT2 performed the worst. uDISCO and 3DISCO induced substantial size reduction on brain sections, and PACT expanded the mouse brain most seriously. Among those methods, ScaleS performed best on fluorescence retention, 3DISCO induced the biggest decline of the fluorescence. PACT achieved the highest increase of imaging depth, and SeeDB and ClearT2 possessed the shallowest imaging depth. This study is expected to provide important reference for users in choosing the most suitable brain optical clearing method.

Autism spectrum disorder (ASD) is characterized by impairment in social communication and the presence of restricted and repetitive behaviors and interests. Executive function impairment is reportedly partially responsible for these symptoms. Executive function includes planning, flexibility, and inhibitory control. Although planning and flexibility in ASD have been consistently reported as atypical, the atypicality of inhibitory control remains controversial. As most previous studies have used nonsocial stimuli to investigate inhibitory control in ASD, the effects of socially relevant information on the inhibitory control system in individuals with ASD remain unclear. Therefore, we developed a go/no-go task with gaze stimuli and measured hemodynamic responses in the right prefrontal cortex (PFC), involved in inhibitory processing in both typically developing (TD) children and children with ASD, using functional near-infrared spectroscopy. Direct gaze induced commission errors to similar extents in both groups. Contrary to the behavioral responses, neural activation in the right PFC was modulated by gaze direction only in the TD group. These findings suggest that the gaze-processing mechanisms in the prefrontal region may be affected by atypical gaze processing in other brain regions during an inhibitory control task with socially relevant information in ASD.

The position of each source and detector “optode” on the scalp, and their relative separations, determines the sensitivity of each functional near-infrared spectroscopy (fNIRS) channel to the underlying cortex. As a result, selecting appropriate scalp locations for the available sources and detectors is critical to every fNIRS experiment. At present, it is standard practice for the user to undertake this task manually; to select what they believe are the best locations on the scalp to place their optodes so as to sample a given cortical region-of-interest (ROI). This process is difficult, time-consuming, and highly subjective. Here, we propose a tool, Array Designer, that is able to automatically design optimized fNIRS arrays given a user-defined ROI and certain features of the available fNIRS device. Critically, the Array Designer methodology is generalizable and will be applicable to almost any subject population or fNIRS device. We describe and validate the algorithmic methodology that underpins Array Designer by running multiple simulations of array design problems in a realistic anatomical model. We believe that Array Designer has the potential to end the need for manual array design, and in doing so save researchers time, improve fNIRS data quality, and promote standardization across the field.