Evaluation of a Compact Hybrid Brain-Computer Interface System.

We realized a compact hybrid brain-computer interface (BCI) system by integrating a portable near-infrared spectroscopy (NIRS) device with an economical electroencephalography (EEG) system. The NIRS array was located on the subjects' forehead, covering the prefrontal area. The EEG electrodes were distributed over the frontal, motor/temporal, and parietal areas. The experimental paradigm involved a Stroop word-picture matching test in combination with mental arithmetic (MA) and baseline (BL) tasks, in which the subjects were asked to perform either MA or BL in response to congruent or incongruent conditions, respectively. We compared the classification accuracies of each of the modalities (NIRS or EEG) with that of the hybrid system. We showed that the hybrid system outperforms the unimodal EEG and NIRS systems by 6.2% and 2.5%, respectively. Since the proposed hybrid system is based on portable platforms, it is not confined to a laboratory environment and has the potential to be used in real-life situations, such as in neurorehabilitation.

A wearable multi-channel fNIRS system for brain imaging in freely moving subjects.

Functional near infrared spectroscopy (fNIRS) is a versatile neuroimaging tool with an increasing acceptance in the neuroimaging community. While often lauded for its portability, most of the fNIRS setups employed in neuroscientific research still impose usage in a laboratory environment. We present a wearable, multi-channel fNIRS imaging system for functional brain imaging in unrestrained settings. The system operates without optical fiber bundles, using eight dual wavelength light emitting diodes and eight electro-optical sensors, which can be placed freely on the subject's head for direct illumination and detection. Its performance is tested on N=8 subjects in a motor execution paradigm performed under three different exercising conditions: (i) during outdoor bicycle riding, (ii) while pedaling on a stationary training bicycle, and (iii) sitting still on the training bicycle. Following left hand gripping, we observe a significant decrease in the deoxyhemoglobin concentration over the contralateral motor cortex in all three conditions. A significant task-related ΔHbO2 increase was seen for the non-pedaling condition. Although the gross movements involved in pedaling and steering a bike induced more motion artifacts than carrying out the same task while sitting still, we found no significant differences in the shape or amplitude of the HbR time courses for outdoor or indoor cycling and sitting still. We demonstrate the general feasibility of using wearable multi-channel NIRS during strenuous exercise in natural, unrestrained settings and discuss the origins and effects of data artifacts. We provide quantitative guidelines for taking condition-dependent signal quality into account to allow the comparison of data across various levels of physical exercise. To the best of our knowledge, this is the first demonstration of functional NIRS brain imaging during an outdoor activity in a real life situation in humans.

Developmental changes in brain activation and functional connectivity during response inhibition in the early childhood brain.

Response inhibition is an attention function which develops relatively early during childhood. Behavioral data suggest that by the age of 3, children master the basic task requirements for the assessment of response inhibition but performance improves substantially until the age of 7. The neuronal mechanisms underlying these developmental processes, however, are not well understood. In this study, we examined brain activation patterns and behavioral performance of children aged between 4 and 6 years compared to adults by applying a go/no-go paradigm during near-infrared spectroscopy (NIRS) brain imaging. We furthermore applied task-independent functional connectivity measures to the imaging data to identify maturation of intrinsic neural functional networks. We found a significant group×condition related interaction in terms of inhibition-related reduced right fronto-parietal activation in children compared to adults. In contrast, motor-related activation did not differ between age groups. Functional connectivity analysis revealed that in the children's group, short-range coherence within frontal areas was stronger, and long-range coherence between frontal and parietal areas was weaker, compared to adults. Our findings show that in children aged from 4 to 6 years fronto-parietal brain maturation plays a crucial part in the cognitive development of response inhibition.

Towards whole-body fluorescence imaging in humans.

Dynamic near-infrared fluorescence (DNIF) whole-body imaging of small animals has become a popular tool in experimental biomedical research. In humans, however, the field of view has been limited to body parts, such as rheumatoid hands, diabetic feet or sentinel lymph nodes. Here we present a new whole-body DNIF-system suitable for adult subjects. We explored whether this system (i) allows dynamic whole-body fluorescence imaging and (ii) can detect modulations in skin perfusion. The non-specific fluorescent probe indocyanine green (ICG) was injected intravenously into two subjects, and fluorescence images were obtained at 5 Hz. The in- and out-flow kinetics of ICG have been shown to correlate with tissue perfusion. To validate the system, skin perfusion was modulated by warming and cooling distinct areas on the chest and the abdomen. Movies of fluorescence images show a bolus passage first in the face, then in the chest, abdomen and finally in the periphery (~10, 15, 20 and 30 seconds, respectively). When skin perfusion is augmented by warming, bolus arrives about 5 seconds earlier than when the skin is cooled and perfusion decreased. Calculating bolus arrival times and spatial fitting of basis time courses extracted from different regions of interest allowed a mapping of local differences in subcutaneous skin perfusion. This experiment is the first to demonstrate the feasibility of whole-body dynamic fluorescence imaging in humans. Since the whole-body approach demonstrates sensitivity to circumscribed alterations in skinperfusion, it may be used to target autonomous changes in polyneuropathy and to screen for peripheral vascular diseases.

A programmable laboratory testbed in support of evaluation of functional brain activation and connectivity.

An important determinant of the value of quantitative neuroimaging studies is the reliability of the derived information, which is a function of the data collection conditions. Near infrared spectroscopy (NIRS) and electroencelphalography are independent sensing domains that are well suited to explore principal elements of the brain's response to neuroactivation, and whose integration supports development of compact, even wearable, systems suitable for use in open environments. In an effort to maximize the translatability and utility of such resources, we have established an experimental laboratory testbed that supports measures and analysis of simulated macroscopic bioelectric and hemodynamic responses of the brain. Principal elements of the testbed include 1) a programmable anthropomorphic head phantom containing a multisignal source array embedded within a matrix that approximates the background optical and bioelectric properties of the brain, 2) integrated translatable headgear that support multimodal studies, and 3) an integrated data analysis environment that supports anatomically based mapping of experiment-derived measures that are directly and not directly observable. Here, we present a description of system components and fabrication, an overview of the analysis environment, and findings from a representative study that document the ability to experimentally validate effective connectivity models based on NIRS tomography.

Somatosensory activation of two fingers can be discriminated with ultrahigh-density diffuse optical tomography.

Topographic non-invasive near infrared spectroscopy (NIRS) has become a well-established tool for functional brain imaging. Applying up to 100 optodes over the head of a subject, allows achieving a spatial resolution in the centimeter range. This resolution is poor compared to other functional imaging tools. However, recently it was shown that diffuse optical tomography (DOT) as an extension of NIRS based on high-density (HD) probe arrays and supplemented by an advanced image reconstruction procedure allows describing activation patterns with a spatial resolution in the millimeter range. Building on these findings, we hypothesize that HD-DOT may render very focal activations accessible which would be missed by the traditionally used sparse arrays. We examined activation patterns in the primary somatosensory cortex, since its somatotopic organization is very fine-grained. We performed a vibrotactile stimulation study of the first and fifth finger in eight human subjects, using a 900-channel continuous-wave DOT imaging system for achieving a higher resolution than conventional topographic NIRS. To compare the results to a well-established high-resolution imaging technique, the same paradigm was investigated in the same subjects by means of functional magnetic resonance imaging (fMRI). In this work, we tested the advantage of ultrahigh-density probe arrays and show that highly focal activations would be missed by classical next-nearest neighbor NIRS approach, but also by DOT, when using a sparse probe array. Distinct activation patterns for both fingers correlated well with the expected neuroanatomy in five of eight subjects. Additionally we show that activation for different fingers is projected to different tissue depths in the DOT image. Comparison to the fMRI data yielded similar activation foci in seven out of ten finger representations in these five subjects when comparing the lateral localization of DOT and fMRI results.

Contrast enhanced high-resolution diffuse optical tomography of the human brain using ICG.

Non-invasive diffuse optical tomography (DOT) of the adult brain has recently been shown to improve the spatial resolution for functional brain imaging applications. Here we show that high-resolution (HR) DOT is also advantageous for clinical perfusion imaging using an optical contrast agent. We present the first HR-DOT results with a continuous wave near infrared spectroscopy setup using a dense grid of optical fibers and indocyanine green (ICG) as an exogenic contrast agent. We find an early arrival of the ICG bolus in the intracerebral tissue and a delayed arrival of the bolus in the extracerebral tissue, achieving the separation of both layers. This demonstrates the method's potential for brain perfusion monitoring in neurointensive care patients.

High-resolution optical functional mapping of the human somatosensory cortex.

Non-invasive optical imaging of brain function has been promoted in a number of fields in which functional magnetic resonance imaging (fMRI) is limited due to constraints induced by the scanning environment. Beyond physiological and psychological research, bedside monitoring and neurorehabilitation may be relevant clinical applications that are yet little explored. A major obstacle to advocate the tool in clinical research is insufficient spatial resolution. Based on a multi-distance high-density optical imaging setup, we here demonstrate a dramatic increase in sensitivity of the method. We show that optical imaging allows for the differentiation between activations of single finger representations in the primary somatosensory cortex (SI). Methodologically our findings confirm results in a pioneering study by Zeff et al. (2007) and extend them to the homuncular organization of SI. After performing a motor task, eight subjects underwent vibrotactile stimulation of the little finger and the thumb. We used a high-density diffuse-optical sensing array in conjunction with optical tomographic reconstruction. Optical imaging disclosed three discrete activation foci one for motor and two discrete foci for vibrotactile stimulation of the first and fifth finger, respectively. The results were co-registered to the individual anatomical brain anatomy (MRI) which confirmed the localization in the expected cortical gyri in four subjects. This advance in spatial resolution opens new perspectives to apply optical imaging in the research on plasticity notably in patients undergoing neurorehabilitation.

Digital-signal-processor-based dynamic imaging system for optical tomography.

In this article, we introduce a dynamic optical tomography system that is, unlike currently available analog instrumentation, based on digital data acquisition and filtering techniques. At the core of this continuous wave instrument is a digital signal processor (DSP) that collects, collates, processes, and filters the digitized data set. The processor is also responsible for managing system timing and the imaging routines which can acquire real-time data at rates as high as 150 Hz. Many of the synchronously timed processes are controlled by a complex programmable logic device that is also used in conjunction with the DSP to orchestrate data flow. The operation of the system is implemented through a comprehensive graphical user interface designed with LABVIEW software which integrates automated calibration, data acquisition, data organization, and signal postprocessing. Performance analysis demonstrates very low system noise (approximately 1 pW rms noise equivalent power), excellent signal precision (<0.04%-0.2%) and long term system stability (<1% over 40 min). A large dynamic range (approximately 190 dB) accommodates a wide scope of measurement geometries and tissue types. First experiments on tissue phantoms show that dynamic behavior is accurately captured and spatial location can be correctly tracked using this system.

Design and implementation of dynamic near-infrared optical tomographic imaging instrumentation for simultaneous dual-breast measurements.

Dynamic near-infrared optical tomographic measurement instrumentation capable of simultaneous bilateral breast imaging, having a capability of four source wavelengths and 32 source-detector fibers for each breast, is described. The system records dynamic optical data simultaneously from both breasts, while verifying proper optical fiber contact with the tissue through implementation of automatic schemes for evaluating data integrity. Factors influencing system complexity and performance are discussed, and experimental measurements are provided to demonstrate the repeatability of the instrumentation. Considerations in experimental design are presented, as well as techniques for avoiding undesirable measurement artifacts, given the high sensitivity and dynamic range (1:10(9)) of the system. We present exemplary clinical results comparing the measured physiologic response of a healthy individual and of a subject with breast cancer to a Valsalva maneuver.