We offer a retrospective report on fNIRS 2018, along with news of the next meeting.

Multimodal imaging combining optoacoustic tomography (OAT) with magnetic resonance imaging (MRI) enables spatiotemporal resolution complementarity, improves accurate quantification, and thus yields more insights into physiology and pathophysiology. However, only manual landmark based coregistration of OAT-MRI has been used so far. We developed a toolbox (RegOA), which frames an automated registration pipeline to align OAT with high-field MR images based on mutual information. We assessed the performance of the registration method using images acquired on one phantom with fiducial markers and in vivo/ex vivo data of mouse heads/brain. The accuracy and robustness of the registration are improved using a two-step registration method with preprocessing of OAT and MRI data. The major advantages of our approach are minimal user input and quantitative assessment of the registration error. The registration with MR and standard reference atlas enables regional information extraction, facilitating the accurate, objective, and rapid analysis of large groups of rodent OAT and MR images.

A detailed theoretical analysis and optimization of high-fidelity, high-frequency firing of the red-shifted very-fast-Chrimson (vf-Chrimson) expressing neurons is presented. A four-state model for vf-Chrimson photocycle has been formulated and incorporated in Hodgkin–Huxley and Wang–Buzsaki spiking neuron circuit models. The effect of various parameters that include irradiance, pulse width, frequency, expression level, and membrane capacitance has been studied in detail. Theoretical simulations are in excellent agreement with recently reported experimental results. The analysis and optimization bring out additional interesting features. A minimal pulse width of 1.7 ms at 23  mW  /  mm² induces a peak photocurrent of 1250 pA. Optimal irradiance (0.1  mW  /  mm²) and pulse width (50  μs) to trigger action potential have been determined. At frequencies beyond 200 Hz, higher values of expression level and irradiance result in spike failure. Singlet and doublet spiking fidelity can be maintained up to 400 and 150 Hz, respectively. The combination of expression level and membrane capacitance is a crucial factor to achieve high-frequency firing above 500 Hz. Its optimization enables 100% spike probability of up to 1 kHz. The study is useful in designing new high-frequency optogenetic neural spiking experiments with desired spatiotemporal resolution, by providing insights into the temporal spike coding, plasticity, and curing neurodegenerative diseases.

Blood vessel injury during image-guided brain biopsy poses a risk of hemorrhage. Approaches that reduce this risk may minimize related patient morbidity. We present here an intraoperative imaging device that has the potential to detect the brain vasculature in situ. The device uses multiple diffuse reflectance spectra acquired in an outward-viewing geometry to detect intravascular hemoglobin, enabling the construction of an optical image in the vicinity of the biopsy needle revealing the proximity to blood vessels. This optical detection system seamlessly integrates into a commercial biopsy system without disrupting the neurosurgical clinical workflow. Using diffusive brain tissue phantoms, we show that this device can detect 0.5-mm diameter absorptive carbon rods up to ∼2  mm from the biopsy window. We also demonstrate feasibility and practicality of the technique in a clinical environment to detect brain vasculature in an in vivo model system. In situ brain vascular detection may add a layer of safety to image-guided biopsies and minimize patient morbidity.

In a pilot study on acute ischemic stroke (AIS) patients, unexpected periodic fluctuations in microvascular cerebral blood flow (CBF) had been observed. Motivated by the relative lack of information about the impact of the emergence of breathing disorders in association with stroke on cerebral hemodynamics, we hypothesized that these fluctuations are due to apneic and hypopneic events. A total of 28 patients were screened within the first week after stroke with a pulse oximeter. Five (18%) showed fluctuations of arterial blood oxygen saturation (≥3  %  ) and were included in the study. Near-infrared diffuse correlation spectroscopy (DCS) was utilized bilaterally to measure the frontal lobe CBF alongside respiratory polygraphy. Biphasic CBF fluctuations were observed with a bilateral increase of 27.1  %    ±  17.7  %   and 29.0  %    ±  17.4  %   for the ipsilesional and contralesional hemispheres, respectively, and a decrease of −19.3  %    ±  9.1  %   and −21.0  %    ±  8.9  %   for the ipsilesional and contralesional hemispheres, respectively. The polygraph revealed that, in general, the fluctuations were associated with apneic and hypopneic events. This study motivates us to investigate whether the impact of altered respiratory patterns on cerebral hemodynamics can be detrimental in AIS patients.

Cerebral asymmetry is considered an important marker of the successful development of the human brain. Recent studies have demonstrated topological asymmetries between structurally hemispheric networks in the human brain. However, it remains largely unknown whether and how the functionally topological asymmetries evolve from childhood to adulthood, a critical period that constitutes the primary peak of human brain and cognitive development. Here, we adopted resting-state functional near-infrared spectroscopy imaging data to construct hemispheric functional networks and then applied graph theory analysis to quantify the topological characteristics of the hemispheric networks. We found that the adult group exhibited consistent leftward hemispheric asymmetries in both global and local network efficiency, and the degree of leftward asymmetry in local network efficiency was significantly increased with development from childhood to adulthood. At the nodal level, the degree of leftward asymmetry in nodal efficiency, mainly involving the frontal, parietal–occipital junction, and occipital regions, increased with development. These developmental patterns of topological asymmetries suggest that the protracted maturation of functional segregation in the left hemisphere could underlie language development from childhood to adulthood and provide insight into the development of human brain functional networks.

Bioluminescence imaging (BLI) is an optical imaging method that can be translated from the cell culture dish in vitro to cell tracking in small animal models in vivo. In contrast to the more widely used fluorescence imaging, which requires light excitation, in BLI the light is exclusively generated by the enzyme luciferase. The luciferase gene can be engineered to target and monitor almost every cell and biological process quantitatively in vitro and even from deep tissue in vivo. While initially used for tumor imaging, bioluminescence was recently optimized for mouse brain imaging of neural cells and monitoring of viability or differentiation of grafted stem cells. Here, we describe the use of bright color-shifted firefly luciferases (Flucs) based on the thermostable x5 Fluc that emit red and green for effective and quantitative unmixing of two human cell populations in vitro and after transplantation into the mouse brain in vivo. Spectral unmixing predicts the ratio of luciferases in vitro and a mixture of cells precisely for cortical grafts, however, with less accuracy for striatal grafts. This dual-color approach enables the simultaneous visualization and quantification of two cell populations on the whole brain scale, with particular relevance for translational studies of neurological disorders providing information on stem cell survival and differentiation in one imaging session in vivo.

The BabyLux device is a hybrid diffuse optical neuromonitor that has been developed and built to be employed in neonatal intensive care unit for the noninvasive, cot-side monitoring of microvascular cerebral blood flow and blood oxygenation. It integrates time-resolved near-infrared and diffuse correlation spectroscopies in a user-friendly device as a prototype for a future medical grade device. We present a thorough characterization of the device performance using test measurements in laboratory settings. Tests on solid phantoms report an accuracy of optical property estimation of about 10%, which is expected when using the photon diffusion equation as the model. The measurement of the optical and dynamic properties is stable during several hours of measurements within 3% of the average value. In addition, these measurements are repeatable between different days of measurement, showing a maximal variation of 5% in the optical properties and 8% for the particle diffusion coefficient on a liquid phantom. The variability over test/retest evaluation is <3  %  . The integration of the two modalities is robust and without any cross talk between the two. We also perform in vivo measurements on the adult forearm during arterial cuff occlusion to show that the device can measure a wide range of tissue hemodynamic parameters. We suggest that this platform can form the basis of the next-generation neonatal neuromonitors to be developed for extensive, multicenter clinical testing.

Executive functions (EFs) associated with the frontal lobe are vital for goal-orientated behavior. To date, limited efforts have been made to examine the relationships among the behavior, brain activation, and topological organization of functional networks in the frontal lobe underlying various EF tasks, including inhibition, working memory, and cognitive flexibility. In this study, functional near-infrared spectroscopy neuroimaging technique was used to systematically inspect the differences in the brain activation and the topological organization of brain networks between various EF tasks in the frontal lobe. In addition, the relationships between brain activation/network properties and task performances and the relationships between brain activation and network properties were, respectively, examined for different EF tasks. Consequently, we have discovered that the nodal and global properties of the resting-state and task-evoked networks, respectively, exhibited significant correlations with the activation of various brain regions during various EF tasks. In particular, the measure that links the neural activation to the topological organization of the brain networks in the frontal lobe can serve as a synergistic indicator to examine the difference between various EF tasks, which paves a way toward a comprehensive understanding of the neural mechanism underlying EFs.

Functional near-infrared spectroscopy (fNIRS) is a noninvasive brain imaging technique to measure evoked changes in cerebral blood oxygenation. In many evoked-task studies, the analysis of fNIRS experiments is based on a temporal linear regression model, which includes block-averaging, deconvolution, and canonical analysis models. The statistical parameters of this model are then spatially mapped across fNIRS measurement channels to infer brain activity. The trade-offs in sensitivity and specificity of using variations of canonical or deconvolution/block-average models are unclear. We quantitatively investigate how the choice of basis set for the regression linear model affects the sensitivity and specificity of fNIRS analysis in the presence of variability or systematic bias in underlying evoked response. For statistical parametric mapping of amplitude-based hypotheses, we conclude that these models are fairly insensitive to the parameters of the regression basis for task durations >10  s and we report the highest sensitivity-specificity results using a low degree-of-freedom canonical model under these conditions. For shorter duration task (<10  s), the signal-to-noise ratio of the data is also important in this decision and we find that deconvolution or block-averaging models outperform the canonical models at high signal-to-noise ratio but not at lower levels.

Communication within the brain is highly dynamic. Alzheimer’s disease (AD) exhibits dynamic progression corresponding to a decline in memory and cognition. However, little is known of whether brain dynamics are disrupted in AD and its prodromal stage, mild cognitive impairment (MCI). For our study, we acquired high sampling rate functional near-infrared spectroscopy imaging data at rest from the entire cortex of 23 patients with AD dementia, 25 patients with amnestic mild cognitive impairment (aMCI), and 30 age-matched healthy controls (HCs). Sliding-window correlation and k-means clustering analyses were used to construct dynamic functional connectivity (FC) maps for each participant. We discovered that the brain’s dynamic FC variability strength (Q) significantly increased in both aMCI and AD group as compared to HCs. Using the Q value as a measurement, the classification performance exhibited a good power in differentiating aMCI [area under the curve (AUC  =  82.5  %  )] or AD (AUC  =  86.4  %  ) from HCs. Furthermore, we identified two abnormal brain FC states in the AD group, of which the occurrence frequency (F) exhibited a significant decrease for the first-level FC state (state 1) and a significant increase for the second-level FC state (state 2). We also found that the abnormal F in these two states significantly correlated with the cognitive impairment in patients. These findings provide the first evidence to demonstrate the disruptions of dynamic brain connectivity in aMCI and AD and extend the traditional static (i.e., time-averaged) FC findings in the disease (i.e., disconnection syndrome) and thus provide insights into understanding the pathophysiological mechanisms occurring in aMCI and AD.

Cognitive flexibility and reward processing critically rely on the orbitofrontal cortex (OFC). Dysregulations in these domains and orbitofrontal activation have been reported in major psychiatric disorders. Hemodynamic brain imaging-informed neurofeedback allows regional-specific control over brain activation and thus may represent an innovative intervention to regulate orbitofrontal dysfunctions. Against this background the present proof-of-concept study evaluates the feasibility and behavioral relevance of functional near-infrared spectroscopy (fNIRS)-assisted neurofeedback training of the lateral orbitofrontal cortex (lOFC). In a randomized sham-controlled between-subject design, 60 healthy participants have undergone four subsequent runs of training to enhance the lOFC activation. Training-induced changes in the lOFC, attentional set-shifting performance, and reward experience have served as primary outcomes. Feedback from the target channel significantly increases the regional-specific lOFC activation over the four training runs in comparison with sham neurofeedback. The real-time OFC neurofeedback group demonstrates a trend for faster responses during the set-shifting relative to the sham neurofeedback group. Within the real-time OFC neurofeedback group, stronger training-induced lOFC increases are associated with higher reward experience. The present results demonstrate that fNIRS-informed neurofeedback allows regional-specific regulation of lOFC activation and may have the potential to modulate the associated behavioral domains. As such fNIRS-informed neurofeedback may represent a promising strategy to regulate OFC dysfunctions in psychiatric disorders.

Directing attention to movement outcomes (external focus; EF), not body movements (internal focus; IF), is a better cognitive strategy for motor performance. However, EF is not effective in some healthy individuals or stroke patients. We aimed to identify the neurological basis reflecting the individual optimal attentional strategy using functional near-infrared spectroscopy. Sixty-four participants (23 healthy young, 23 healthy elderly, and 18 acute stroke) performed a reaching movement task under IF and EF conditions. Of these, 13 healthy young participants, 11 healthy elderly participants, and 6 stroke patients showed better motor performance under EF conditions (EF-dominant), whereas the others showed IF-dominance. We then measured prefrontal activity during rhythmic hand movements under both attentional conditions. IF-dominant participants showed significantly higher left prefrontal activity than EF-dominant participants under IF condition. In addition, receiver operating characteristic analysis supported that the higher activity in the left frontopolar and dorsolateral prefrontal cortices could detect IF-dominance as an individual’s optimal attentional strategy for preventing motor performance decline. Taken together, these results suggest that prefrontal activity during motor tasks reflects an individual’s ability to process internal body information, thereby conferring IF-dominance. These findings could be applied for the development of individually optimized rehabilitation programs.

Noninvasive transcranial photobiomodulation (tPBM) with a 1064-nm laser has been reported to improve human performance on cognitive tasks as well as locally upregulate cerebral oxygen metabolism and hemodynamics. However, it is unknown whether 1064-nm tPBM also modulates electrophysiology, and specifically neural oscillations, in the human brain. The hypothesis guiding our study is that applying 1064-nm tPBM of the right prefrontal cortex enhances neurophysiological rhythms at specific frequency bands in the human brain under resting conditions. To test this hypothesis, we recorded the 64-channel scalp electroencephalogram (EEG) before, during, and after the application of 11 min of 4-cm-diameter tPBM (CW 1064-nm laser with 162  mW  /  cm² and 107  J  /  cm²) to the right forehead of human subjects (n  =  20) using a within-subject, sham-controlled design. Time-resolved scalp topographies of EEG power at five frequency bands were computed to examine the tPBM-induced EEG power changes across the scalp. The results show time-dependent, significant increases of EEG spectral powers at the alpha (8 to 13 Hz) and beta (13 to 30 Hz) bands at broad scalp regions, exhibiting a front-to-back pattern. The findings provide the first sham-controlled topographic mapping that tPBM increases the strength of electrophysiological oscillations (alpha and beta bands) while also shedding light on the mechanisms of tPBM in the human brain.

We employ transcranial wide-field single-photon imaging to compare genetically encoded calcium sensors under transgenic or viral vector expression strategies. Awake, head-fixed animals and brief visual flash stimuli are used to assess function. The use of awake transcranial imaging may reduce confounds attributed to cranial window implantation or anesthesia states. We report differences in wide-field epifluorescence brightness and peak ΔF  /  F₀ response to visual stimulation between expression strategies. Other metrics for indicator performance include fluctuation analysis (standard deviation) and regional correlation maps made from spontaneous activity. We suggest that multiple measures, such as stimulus-evoked signal-to-noise ratio, brightness, and averaged visual ΔF  /  F₀ response, may be necessary to characterize indicator sensitivity and methods of expression. Furthermore, we show that strategies using blood brain barrier-permeable viruses, such as PHP.eB, yield comparable expression and function as those derived from transgenic mice. We suggest that testing of new genetically engineered activity sensors could employ a single-photon, wide-field imaging pipeline involving visual stimulation in awake mice that have been intravenously injected with PHP.eB.