Brain activation during neurocognitive testing using functional near-infrared spectroscopy in patients following concussion compared to healthy controls.

There is no accepted clinical imaging modality for concussion, and current imaging modalities including fMRI, DTI, and PET are expensive and inaccessible to most clinics/patients. Functional near-infrared spectroscopy (fNIRS) is a non-invasive, portable, and low-cost imaging modality that can measure brain activity. The purpose of this study was to compare brain activity as measured by fNIRS in concussed and age-matched controls during the performance of cognitive tasks from a computerized neurocognitive test battery. Participants included nine currently symptomatic patients aged 18-45 years with a recent (15-45 days) sport-related concussion and five age-matched healthy controls. The participants completed a computerized neurocognitive test battery while wearing the fNIRS unit. Our results demonstrated reduced brain activation in the concussed subject group during word memory, (spatial) design memory, digit-symbol substitution (symbol match), and working memory (X's and O's) tasks. Behavioral performance (percent-correct and reaction time respectively) was lower for concussed participants on the word memory, design memory, and symbol match tasks than controls. The results of this preliminary study suggest that fNIRS could be a useful, portable assessment tool to assess reduced brain activation and augment current approaches to assessment and management of patients following concussion.

Neuroimaging to detect cortical projection of vestibular response to caloric stimulation in young and older adults using functional near-infrared spectroscopy (fNIRS).

Functional near-infrared spectroscopy (fNIRS) is a non-invasive and portable neuroimaging technique. The method uses non-ionizing laser light in the range of red to near-infrared to detect changes in cerebral blood oxygenation. In this study, we used fNIRS to investigate cortical hemodynamic changes in the temporo-parietal and frontal regions during caloric vestibular stimulation. Caloric stimulation has previously been investigated using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), which serves as a validation of the fNIRS imaging modality toward the measurement of vestibular related brain regions. To date, only a single study has used fNIRS during caloric irrigations, which observed blood volume changes in the temporal-parietal area in healthy younger subjects. In this current study, fNIRS was used to measure cortical vestibular activation in 10 right-handed younger subjects (5 male and 5 female, age 25+/-6 years) and 10 right-handed older subjects (6 male and 4 female, age 74+/-5 years). We investigated both warm (44 °C) and cool (30 °C) unilateral caloric vestibular stimulation. Consistent with previous reports, we found that warm (44 °C) caloric irrigation caused a bilateral activation. In addition, we found that cool (30 °C) caloric irrigation caused contralateral activation of the temporo-parietal area. This study is the first to investigate age effects of the caloric stimulation on brain activity. We found that the older subjects had stronger bilateral effects than the younger subjects. Our results confirm previous fMRI and PET studies that showed cortical activation during caloric vestibular irrigation is dependent on side of irrigation, and temperature of irrigation. Furthermore, our results demonstrate that fNIRS is a viable technique in measuring cortical effects during vestibular tasks.

Topographic localization of brain activation in diffuse optical imaging using spherical wavelets.

Diffuse optical imaging is a non-invasive technique that uses near-infrared light to measure changes in brain activity through an array of sensors placed on the surface of the head. Compared to functional MRI, optical imaging has the advantage of being portable while offering the ability to record functional changes in both oxy- and deoxy-hemoglobin within the brain at a high temporal resolution. However, the reconstruction of accurate spatial images of brain activity from optical measurements represents an ill-posed and underdetermined problem that requires regularization. These reconstructions benefit from incorporating prior information about the underlying spatial structure and function of the brain. In this work, we describe a novel image reconstruction approach which uses surface-based wavelets derived from structural MRI to incorporate high-resolution anatomical and structural prior information about the brain. This surface-based approach is used to approximate brain activation patterns through the reconstruction and presentation of topographical (two-dimensional) maps of brain activation directly onto the folded surface of the cortex. The set of wavelet coefficients is directly estimated by a truncated singular-value decomposition based pseudo-inversion of the wavelet projection of the optical forward model. We use a reconstruction metric based on Shannon entropy which quantifies the sparse loading of the wavelet coefficients and is used to determine the optimal truncation and regularization of this inverse model. In this work, examples of the performance of this model are illustrated for several cases of numerical simulation and experimental data with comparison to functional magnetic resonance imaging.

Exploring neuro-vascular and neuro-metabolic coupling in rat somatosensory cortex.

The existence of a coupling between changes in neuronal activity, cerebral blood flow and blood oxygenation is well known. The explicit relationship between these systems, however, is complex and remains a subject of intense research. Here, we use direct electrophysiological recordings to predict blood flow and oxygenation changes measured with optical methods during parametric stimulation applied to the somatosensory cortex in rat brain. Using a multimodal model of the cerebral functional unit, we estimate a neuro-vascular and a neuro-metabolic transfer function relating the experimentally measured neural responses with the inputs to a vascular model predicting hemodynamic and blood oxygenation changes. We show that our model can accurately predict experimentally measured parametric hemodynamic evoked responses by using a single linear transfer function relationship with a reduced number of state parameters to relate the level of neural activity to evoked cerebral blood flow and oxygen metabolism changes. At the same time, we characterize the metabolic and vascular neural response functions and interpret their physiological significance.

A temporal comparison of BOLD, ASL, and NIRS hemodynamic responses to motor stimuli in adult humans.

In this study, we have preformed simultaneous near-infrared spectroscopy (NIRS) along with BOLD (blood oxygen level dependent) and ASL (arterial spin labeling)-based fMRI during an event-related motor activity in human subjects in order to compare the temporal dynamics of the hemodynamic responses recorded in each method. These measurements have allowed us to examine the validity of the biophysical models underlying each modality and, as a result, gain greater insight into the hemodynamic responses to neuronal activation. Although prior studies have examined the relationships between these two methodologies through similar experiments, they have produced conflicting results in the literature for a variety of reasons. Here, by employing a short-duration, event-related motor task, we have been able to emphasize the subtle temporal differences between the hemodynamic parameters with a high contrast-to-noise ratio. As a result of this improved experimental design, we are able to report that the fMRI measured BOLD response is more correlated with the NIRS measure of deoxy-hemoglobin (R = 0.98; P < 10(-20)) than with oxy-hemoglobin (R = 0.71), or total hemoglobin (R = 0.53). This result was predicted from the theoretical grounds of the BOLD response and is in agreement with several previous works [Toronov, V.A.W., Choi, J.H., Wolf, M., Michalos, A., Gratton, E., Hueber, D., 2001. "Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging." Med. Phys. 28 (4) 521-527.; MacIntosh, B.J., Klassen, L.M., Menon, R.S., 2003. "Transient hemodynamics during a breath hold challenge in a two part functional imaging study with simultaneous near-infrared spectroscopy in adult humans". NeuroImage 20 1246-1252.; Toronov, V.A.W., Walker, S., Gupta, R., Choi, J.H., Gratton, E., Hueber, D., Webb, A., 2003. "The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal" Neuroimage 19 (4) 1521-1531]. These data have also allowed us to examine more detailed measurement models of the fMRI signal and comment on the roles of the oxygen saturation and blood volume contributions to the BOLD response. In addition, we found high correlation between the NIRS measured total hemoglobin and ASL measured cerebral blood flow (R = 0.91; P < 10(-10)) and oxy-hemoglobin with flow (R = 0.83; P < 10(-05)) as predicted by the biophysical models. Finally, we note a significant amount of cross-modality, correlated, inter-subject variability in amplitude change and time-to-peak of the hemodynamic response. The observed co-variance in these parameters between subjects is in agreement with hemodynamic models and provides further support that fMRI and NIRS have similar vascular sensitivity.