Visuospatial task-related prefrontal activity is correlated with negative symptoms in schizophrenia.

Control of attention is thought to be specifically impaired in schizophrenia due to abnormal function in the prefrontal cortex (PFC). The PFC plays a critical role in the identification of relevant stimuli and the development of appropriate biases for the identified signals, including selection of an appropriate attentional 'zoom'. We examined how demands associated with changes in attentional requirements in a Sustained Attention Task (SAT) may contribute to differences in functional involvement of the PFC and relation to clinical status. A group of 24 individuals with schizophrenia and 16 healthy controls (N = 40) performed the SAT and a visuospatial condition (vSAT) while activity in the bilateral anterior PFC was monitored using functional Near Infrared Spectroscopy (fNIRS). The results confirm that the right frontopolar region plays a role in control of attention for both patients and healthy controls. However, patients with schizophrenia exhibited a general attentional deficit and inefficient right-medial PFC activation. Additionally, we observed a strong regional association between left Middle Frontal Gyrus (MFG) activity during the vSAT task and the PANSS score driven by the negative symptom subscale. The presence of aberrant activation differences within the left-MFG region may describe a dysregulation of attentional networks linked to the clinical expression of negative and general symptoms.

A Systematic Review of Integrated Functional Near-Infrared Spectroscopy (fNIRS) and Transcranial Magnetic Stimulation (TMS) Studies.

Background: The capacity for TMS to elicit neural activity and manipulate cortical excitability has created significant expectation regarding its use in both cognitive and clinical neuroscience. However, the absence of an ability to quantify stimulation effects, particularly outside of the motor cortex, has led clinicians and researchers to pair noninvasive brain stimulation with noninvasive neuroimaging techniques. fNIRS, as an optical and wearable neuroimaging technique, is an ideal candidate for integrated use with TMS. Together, TMS+fNIRS may offer a hybrid alternative to "blind" stimulation to assess NIBS in therapy and research. Objective: In this systematic review, the current body of research into the transient and prolonged effects of TMS on fNIRS-based cortical hemodynamic measures while at rest and during tasks are discussed. Additionally, studies investigating the relation of fNIRS to measures of cortical excitability as produced by TMS-evoked Motor-Evoked-Potential (MEP) are evaluated. The aim of this review is to outline the integrated use of TMS+fNIRS and consolidate findings related to use of fNIRS to monitor changes attributed to TMS and the relationship of fNIRS to cortical excitability itself. Methods: Key terms were searched in PubMed and Web-of-Science to identify studies investigating the use of both fNIRS and TMS. Works from Google-Scholar and referenced works in identified papers were also assessed for relevance. All published experimental studies using both fNIRS and TMS techniques in the study methodology were included. Results: A combined literature search of neuroimaging and neurostimulation studies identified 53 papers detailing the joint use of fNIRS and TMS. 22/53 investigated the immediate effects of TMS at rest in the DLPFC and M1 as measured by fNIRS. 21/22 studies reported a significant effect in [HbO] for 40/54 stimulation conditions with 14 resulting an increase and 26 in a decrease. While 15/22 studies also reported [HbR], only 5/37 conditions were significant. Task effects of fNIRS+TMS were detailed in 16 studies, including 10 with clinical populations. Most studies only reported significant changes in [HbO] related measures. Studies comparing fNIRS to changes in MEP-measured cortical excitability suggest that fNIRS measures may be spatially more diffuse but share similar traits. Conclusion: This review summarizes the progress in the development of this emerging hybrid neuroimaging & neurostimulation methodology and its applications. Despite encouraging progress and novel applications, a lack of replicated works, along with highly disparate methodological approaches, highlight the need for further controlled studies. Interpretation of current research directions, technical challenges of TMS+fNIRS, and recommendations regarding future works are discussed.

Early diagnosis of traumatic intracranial hematomas.

Timing of the intervention for intracranial hematomas is critical for its success, specifically since expansion of the hemorrhage can result in debilitating and sometimes fatal outcomes. Led by Britton Chance, we and an extended team from University of Pennsylvania, Baylor and Drexel universities developed a handheld brain hematoma detector for early triage and diagnosis of head trauma victims. After obtaining de novo Food and Drug Administration clearance, over 200 systems are deployed in all Marine battalion aid stations around the world. Infrascanner, a handheld brain hematoma detection system, is based on the differential near-infrared light absorption of the injured versus the noninjured part of brain. About 12 independent studies have been conducted in the USA, Canada, Spain, Italy, the Netherlands, Germany, Russia, Poland, Afghanistan, India, China, and Turkey. Here, we outline the background and design of the device as well as clinical studies with a total of 1293 patients and 203 hematomas. Infrascanner demonstrates high sensitivity (adults: 92.5% and children: 93%) and specificity (adults: 82.9% and children: 86.5%) in detecting intracranial hematomas >3.5 mL in volume and <2.5 cm from the surface of the brain. Infrascanner is a clinically effective screening solution for head trauma patients in prehospital settings where timely triage is critical.

Performance Monitoring via Functional Near Infrared Spectroscopy for Virtual Reality Based Basic Life Support Training.

The use of serious game tools in training of medical professions is steadily growing. However, there is a lack of reliable performance assessment methods to evaluate learner's outcome. The aim of this study is to determine whether functional near infrared spectroscopy (fNIRS) can be used as an additional tool for assessing the learning outcome of virtual reality (VR) based learning modules. The hypothesis is that together with an improvement in learning outcome there would be a decrease in the participants' cerebral oxygenation levels measured from the prefrontal cortex (PFC) region and an increase of participants' serious gaming results. To test this hypothesis, the subjects were recruited and divided into four groups with different combinations of prior virtual reality experience and prior Basic Life Support (BLS) knowledge levels. A VR based serious gaming module for teaching BLS and 16-Channel fNIRS system were used to collect data from the participants. Results of the participants' scores acquired from the serious gaming module were compared with fNIRS measures on the initial and final training sessions. Kruskal Wallis test was run to determine any significant statistical difference between the groups and Mann-Whitney U test was utilized to obtain pairwise comparisons. BLS training scores of the participants acquired from VR based serious game's the learning management system and fNIRS measurements revealed decrease in use of resources from the PFC, but increase in behavioral performance. Importantly, brain-based measures can provide an additional quantitative metric for trainee's expertise development and can assist the medical simulation instructors.

Evaluation of light detector surface area for functional Near Infrared Spectroscopy.

Functional Near Infrared Spectroscopy (fNIRS) is an emerging neuroimaging technique that utilizes near infrared light to detect cortical concentration changes of oxy-hemoglobin and deoxy-hemoglobin non-invasively. Using light sources and detectors over the scalp, multi-wavelength light intensities are recorded as time series and converted to concentration changes of hemoglobin via modified Beer-Lambert law. Here, we describe a potential source for systematic error in the calculation of hemoglobin changes and light intensity measurements. Previous system characterization and analysis studies looked into various fNIRS parameters such as type of light source, number and selection of wavelengths, distance between light source and detector. In this study, we have analyzed the contribution of light detector surface area to the overall outcome. Results from Monte Carlo based digital phantoms indicated that selection of detector area is a critical system parameter in minimizing the error in concentration calculations. The findings here can guide the design of future fNIRS sensors.

Evaluation of evoked responses to pulse-matched high frequency and intermittent theta burst transcranial magnetic stimulation using simultaneous functional near-infrared spectroscopy.

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.

Measuring speaker-listener neural coupling with functional near infrared spectroscopy.

The present study investigates brain-to-brain coupling, defined as inter-subject correlations in the hemodynamic response, during natural verbal communication. We used functional near-infrared spectroscopy (fNIRS) to record brain activity of 3 speakers telling stories and 15 listeners comprehending audio recordings of these stories. Listeners' brain activity was significantly correlated with speakers' with a delay. This between-brain correlation disappeared when verbal communication failed. We further compared the fNIRS and functional Magnetic Resonance Imaging (fMRI) recordings of listeners comprehending the same story and found a significant relationship between the fNIRS oxygenated-hemoglobin concentration changes and the fMRI BOLD in brain areas associated with speech comprehension. This correlation between fNIRS and fMRI was only present when data from the same story were compared between the two modalities and vanished when data from different stories were compared; this cross-modality consistency further highlights the reliability of the spatiotemporal brain activation pattern as a measure of story comprehension. Our findings suggest that fNIRS can be used for investigating brain-to-brain coupling during verbal communication in natural settings.

A long academic journey.

In this case study, an early-career electrical engineer interviews an established translational biomedical engineer. The discussion covered topics such as challenges associated with the merging of fundamental engineering science with the pursuit of clinically informed research, how best to train engineering students for future innovation, and how to establish international partnerships.

Functional near-infrared spectroscopy for the measurement of propofol effects in conscious sedation during outpatient elective colonoscopy.

Endoscopic procedures performed in the United States routinely involve the use of conscious sedation as standard of care. The use of sedation reduces patient discomfort and anxiety while improving the technical quality of the procedure, and as a result, over 98% of clinicians have adopted the practice. The tremendous benefits of sedation are offset by heightened costs, increased patient discharge time, and cardiopulmonary complication risks. The inherent liabilities of putting patients under sedation have necessitated a large number of physiological monitoring systems in order to ensure patient comfort and safety. Currently American Society of Anesthesiologist (ASA) guidelines recommend monitoring of pulse oximetry, blood pressure, heart rate, and end-tidal CO2; although important safeguards, these physiological measurements do not allow for the reliable assessment of patient sedation. Proper monitoring of patient state ensures procedure quality and patient safety; however no "gold-standard" is available to determine the depth of sedation which is comparable to the anesthesiologist's professional judgment. Developments in functional near-infrared spectroscopy (fNIRS) over the past two decades have introduced cost-effective, portable, and non-invasive neuroimaging tools which measure cortical hemodynamic activity as a correlate of neural functions. Anesthetic drugs, such as propofol, operate by suppressing cerebral metabolism. fNIRS imaging methods have the ability to detect these drug related effects as well as neuronal activity through the measurement of local cerebral hemodynamic changes. In the present study, 41 patients were continuously monitored using fNIRS while undergoing outpatient elective colonoscopy with propofol sedation. The preliminary results indicated that oxygenated hemoglobin changes in the dorsolateral prefrontal cortex, as assessed by fNIRS were correlated with changes in response to bolus infusions of propofol, whereas other standard physiological measures were not significantly associated.

Molecular concentration of deoxyHb in human prefrontal cortex predicts the emergence and suppression of consciousness.

This is the first study to use fNIRS to explore anaesthetic depth and awakening during surgery with general anaesthesia. A 16 channel continuous wave (CW) functional near-infrared system (fNIRS) was used to monitor PFC activity. These outcomes were compared to BIS measures. The results indicate that deoxyHb concentration in the PFC varies during the suppression and emergence of consciousness. During suppression, deoxyHb levels increase, signalling the deactivation of the PFC, while during emergence, deoxyHb concentration drops, initiating PFC activation and the recovery of consciousness. Furthermore, BIS and deoxyHb concentrations in the PFC display a high negative correlation throughout the different anaesthetic phases. These findings suggest that deoxyHb could be a reliable marker for monitoring anaesthetic depth, and that the PFC intervenes in the suppression and emergence of consciousness.

A functional near-infrared spectroscopy study of lexical decision task supports the dual route model and the phonological deficit theory of dyslexia.

The dual route model (DRM) of reading suggests two routes of reading development: the phonological and the orthographic routes. It was proposed that although the two routes are active in the process of reading; the first is more involved at the initial stages of reading acquisition, whereas the latter needs more reading training to mature. A number of studies have shown that deficient phonological processing is a core deficit in developmental dyslexia. According to the DRM, when the Lexical Decision Task (LDT) is performed, the orthographic route should also be involved when decoding words, whereas it is clear that when decoding pseudowords the phonological route should be activated. Previous functional near-infrared spectroscopy (fNIR) studies have suggested that the upper left frontal lobe is involved in decision making in the LDT. The current study used fNIR to compare left frontal lobe activity during LDT performance among three reading-level groups: 12-year-old children, young adult dyslexic readers, and young adult typical readers. Compared to typical readers, the children demonstrated lower activity under the word condition only, whereas the dyslexic readers showed lower activity under the pseudoword condition only. The results provide evidence for upper left frontal lobe involvement in LDT and support the DRM and the phonological deficit theory of dyslexia.

Verbal working memory impairments following traumatic brain injury: an fNIRS investigation.

The construct of working memory and its reliance on dorsolateral prefrontal cortex (DLPFC) have been the focus of many studies in healthy subjects and in clinical populations. However, transfer of knowledge gained from cognitive science studies to clinical applications can be a challenging goal. This scarce cross-dissemination may be partially due to the use of 'tools' that are limited in their ability to generate meaningful information about impairments in clinical groups. To this end, this paper investigates the use of functional near-infrared spectroscopy (fNIRS), which offers unique opportunities for recording neuroactivation. Specifically, we examine measures of the DLPFC hemodynamic response during a working memory task in adults with traumatic brain injury (TBI) and healthy controls. Analysis of hemodynamic measures showed significant differences between the two groups, even without differences in behavioral performance. Additional subtle disparities were linked to levels of performance in TBI and healthy subjects. fNIRS hemodynamic measures may therefore provide novel information to existing theories and knowledge of the working memory construct. Future studies may further define these subtle differences captured by fNIRS to help identify which components affect inter-individual variations in performance and could play a contributing role in the choice and planning of neurorehabilitation interventions targeting working memory.

Continuous monitoring of brain dynamics with functional near infrared spectroscopy as a tool for neuroergonomic research: empirical examples and a technological development.

Functional near infrared spectroscopy (fNIRS) is a non-invasive, safe, and portable optical neuroimaging method that can be used to assess brain dynamics during skill acquisition and performance of complex work and everyday tasks. In this paper we describe neuroergonomic studies that illustrate the use of fNIRS in the examination of training-related brain dynamics and human performance assessment. We describe results of studies investigating cognitive workload in air traffic controllers, acquisition of dual verbal-spatial working memory skill, and development of expertise in piloting unmanned vehicles. These studies used conventional fNIRS devices in which the participants were tethered to the device while seated at a workstation. Consistent with the aims of mobile brain imaging (MoBI), we also describe a compact and battery-operated wireless fNIRS system that performs with similar accuracy as other established fNIRS devices. Our results indicate that both wired and wireless fNIRS systems allow for the examination of brain function in naturalistic settings, and thus are suitable for reliable human performance monitoring and training assessment.

A working memory deficit among dyslexic readers with no phonological impairment as measured using the n-back task: an fNIR study.

Data indicated that dyslexic individuals exhibited difficulties on tasks involving Working Memory (WM). Previous studies have suggested that these deficits stem from impaired processing in the Phonological Loop (PL). The PL impairment was connected to poor phonological processing. However, recent data has pointed to the Central Executive (CE) system as another source of WM deficit in dyslexic readers. This opened a debate whether the WM deficit stems solely from PL or can also be seen as an outcome of poor CE processing. In an attempt to verify this question, the current study compared adult skilled and compensated dyslexic readers with no impairment of phonological skills. The participants' PL and CE processing were tested by using the fNIR device attached to the frontal lobe and measured the changes in brain oxygen values when performing N-back task. As it was previously suggested, the N = 0 represented PL and N = 1 to 3 represent CE processing. It was hypothesized that dyslexic readers who show non-impaired phonological skills will exhibit deficits mainly in the CE subsystem and to a lesser extent in the PL. Results indicated that the two reading level groups did not differ in their accuracy and reaction times in any of the N-Back conditions. However, the dyslexic readers demonstrated significant lower maximum oxyHb values in the upper left frontal lobe, mainly caused due to a significant lower activity under the N = 1 condition. Significant task effects were found in the medial left hemisphere, and the high medial right hemisphere. In addition, significant correlations between fNIR-features, reading performance and speed of processing were found. The higher oxyHb values, the better reading and speed of processing performance obtained. The results of the current study support the hypothesis that at least for the group of dyslexics with non-impaired PL, WM deficit stems from poor CE activity.

A methodology for validating artifact removal techniques for physiological signals.

Artifact removal from physiological signals is an essential component of the biosignal processing pipeline. The need for powerful and robust methods for this process has become particularly acute as healthcare technology deployment undergoes transition from the current hospital-centric setting toward a wearable and ubiquitous monitoring environment. Currently, determining the relative efficacy and performance of the multiple artifact removal techniques available on real world data can be problematic, due to incomplete information on the uncorrupted desired signal. The majority of techniques are presently evaluated using simulated data, and therefore, the quality of the conclusions is contingent on the fidelity of the model used. Consequently, in the biomedical signal processing community, there is considerable focus on the generation and validation of appropriate signal models for use in artifact suppression. Most approaches rely on mathematical models which capture suitable approximations to the signal dynamics or underlying physiology and, therefore, introduce some uncertainty to subsequent predictions of algorithm performance. This paper describes a more empirical approach to the modeling of the desired signal that we demonstrate for functional brain monitoring tasks which allows for the procurement of a "ground truth" signal which is highly correlated to a true desired signal that has been contaminated with artifacts. The availability of this "ground truth," together with the corrupted signal, can then aid in determining the efficacy of selected artifact removal techniques. A number of commonly implemented artifact removal techniques were evaluated using the described methodology to validate the proposed novel test platform.

Frontal lobe role in simple arithmetic calculations: an fNIR study.

This study aimed to affirm the use of functional near-infrared spectroscopy (fNIR) in examining frontal lobe role during automatic (i.e., requires retrieval from long-term memory) and method-based (i.e., requires calculation) arithmetic processing. Adult university students (math difficulties [MD] and control) performed simple arithmetic calculations while monitored using an fNIR system designed to image regions within the frontal cortices. Addition and subtraction problems presented on a computer screen belonged to one of three categories: triples "under 10" (e.g., 2+3=?, 5-3=?), triples that "break 10" (e.g., 5+8=?, 13-5=?), or triples "including 10" (e.g., 10+7=?, 17-10=?). fNIR recordings indicated significant interactions between type of triple, operation, and group over left frontal lobe, and between type of triple and group over right frontal lobe. Within-group differences among controls were found in the "break 10" triples with higher DeOxyHb level recorded during subtraction processing. Between-group differences were found in the "break 10" and "including 10" triples for subtraction with higher levels of DeOxyHb recorded among controls. Results imply that among adults frontal lobe is still involved during simple mathematical processing and fNIR recordings can differentiate its role in adults of varying mathematical ability.

A P300-based EEG-BCI for spatial navigation control.

In this study, a Brain Computer Interface (BCI) based on the P300 oddball paradigm has been developed for spatial navigation control in virtual environments. Functionality and efficacy of the system were analyzed with results from nine healthy volunteers. Each participant was asked to gaze at an individual target in a 3×3 P300 matrix containing different symbolic navigational icons while EEG signals were collected. Resulting ERPs were processed online and classification commands were executed to control spatial movements within the MazeSuite virtual environment and presented to the user online during an experiment. Subjects demonstrated on average, ∼89% online accuracy for simple mazes and ∼82% online accuracy in longer more complex mazes. Results suggest that this BCI setup enables guided free-form navigation in virtual 3D environments.

Detection of attention shift for asynchronous P300-based BCI.

Brain-computer interface (BCI) provides patients suffering from severe neuromuscular disorders an alternative way of interacting with the outside world. The P300-based BCI is among the most popular paradigms in the field and most current versions operate in synchronous mode and assume participant engagement throughout operation. In this study, we demonstrate a new approach for assessment of user engagement through a hybrid classification of ERP and band power features of EEG signals that could allow building asynchronous BCIs. EEG signals from nine electrode locations were recorded from nine participants during controlled engagement conditions when subjects were either engaged with the P3speller task or not attending. Statistical analysis of band power showed that there were significant contrasts of attending only for the delta and beta bands as indicators of features for user attendance classification. A hybrid classifier using ERP scores and band power features yielded the best overall performance of 0.98 in terms of the area under the ROC curve (AUC). Results indicate that band powers can provide additional discriminant information to the ERP for user attention detection and this combined approach can be used to assess user engagement for each stimulus sequence during BCI use.

Tangram solved? Prefrontal cortex activation analysis during geometric problem solving.

Recent neuroimaging studies have implicated prefrontal and parietal cortices for mathematical problem solving. Mental arithmetic tasks have been used extensively to study neural correlates of mathematical reasoning. In the present study we used geometric problem sets (tangram tasks) that require executive planning and visuospatial reasoning without any linguistic representation interference. We used portable optical brain imaging (functional near infrared spectroscopy--fNIR) to monitor hemodynamic changes within anterior prefrontal cortex during tangram tasks. Twelve healthy subjects were asked to solve a series of computerized tangram puzzles and control tasks that required same geometric shape manipulation without problem solving. Total hemoglobin (HbT) concentration changes indicated a significant increase during tangram problem solving in the right hemisphere. Moreover, HbT changes during failed trials (when no solution found) were significantly higher compared to successful trials. These preliminary results suggest that fNIR can be used to assess cortical activation changes induced by geometric problem solving. Since fNIR is safe, wearable and can be used in ecologically valid environments such as classrooms, this neuroimaging tool may help to improve and optimize learning in educational settings.