Separating Signal from Noise in High-Density Diffuse Optical Tomography

High-density diffuse optical tomography (HD-DOT) is a relatively new neuroimaging technique that detects the changes in hemoglobin concentrations following neuronal activity through the measurement of near-infrared light intensities. Thus, it has the potential to be a surrogate for functional MRI (fMRI) as a more naturalistic, portable, and cost-effective neuroimaging system. As in other neuroimaging modalities, head motion is the most common source of noise in HD-DOT data that results in spurious effects in the functional brain images. Unlike other neuroimaging modalities, data quality assessment methods are still underdeveloped for HD-DOT. Therefore, developing robust motion detection and motion removal methods in its data processing pipeline is a crucial step for making HD-DOT a reliable neuroimaging modality. In particular, our lab is interested in using HD-DOT to study the brain function in clinical populations with metal implants that cannot be studied using fMRI due to their contraindications. Two of these populations are patients having movement disorders (Parkinson Disease or essential tremor) with deep brain stimulation (DBS) implants and individuals with cochlear implants (CI). These two groups both receive tremendous benefit from their implants at the statistical level; however, there is significant single-subject variability. Our overarching goal is to use HD-DOT to find the relationships between the neuronal function and the behavioral measures in these populations to optimize the contact location of these implant surgeries. However, one of the challenges in analyzing the data in these subjects, especially in patients with DBS, is their high levels of motion due to tremors when their DBS implant is turned off. This further motivates the importance of the methods presented herein for separating signal from noise in HD-DOT data. To this end, I will first assess the efficacy of state-of-the-art motion correction methods introduced in the fNIRS literature for HD-DOT. Then, I will present a novel global metric inspired by motion detection methods in fMRI called GVTD (global variance of the temporal derivatives). Our results show that GVTD-based motion detection not only outperforms other comparable motion detection methods in fNIRS, but also outperforms motion detection with accelerometers. I will then present my work on collecting and processing HD-DOT data for two clinical populations with metal implants in their brain and the preliminary results for these studies. Our results in PD patients show that HD-DOT can reliably map neuronal activity in this group and replicate previously published results using PET and fMRI. Our results in the CI users provide evidence for the recruitment of the prefrontal cortex in processing speech to compensate for the decreased activity in the temporal cortex. These findings support the theory of cognitive demand increase in effortful listening situations. In summary, the presented methods for separating signal from noise enable direct comparisons of HD-DOT images with those of fMRI in clinical populations with metal implants and equip this modality to be used as a surrogate for fMRI

Prefrontal cortex supports speech perception in listeners with cochlear implants

Cochlear implants are neuroprosthetic devices that can restore hearing in people with severe to profound hearing loss by electrically stimulating the auditory nerve. Because of physical limitations on the precision of this stimulation, the acoustic information delivered by a cochlear implant does not convey the same level of acoustic detail as that conveyed by normal hearing. As a result, speech understanding in listeners with cochlear implants is typically poorer and more effortful than in listeners with normal hearing. The brain networks supporting speech understanding in listeners with cochlear implants are not well understood, partly due to difficulties obtaining functional neuroimaging data in this population. In the current study, we assessed the brain regions supporting spoken word understanding in adult listeners with right unilateral cochlear implants (n=20) and matched controls (n=18) using high-density diffuse optical tomography (HD-DOT), a quiet and non-invasive imaging modality with spatial resolution comparable to that of functional MRI. We found that while listening to spoken words in quiet, listeners with cochlear implants showed greater activity in the left prefrontal cortex than listeners with normal hearing, specifically in a region engaged in a separate spatial working memory task. These results suggest that listeners with cochlear implants require greater cognitive processing during speech understanding than listeners with normal hearing, supported by compensatory recruitment of the left prefrontal cortex

Portable, field-based neuroimaging using high-density diffuse optical tomography

Behavioral and cognitive tests in individuals who were malnourished as children have revealed malnutrition-related deficits that persist throughout the lifespan. These findings have motivated recent neuroimaging investigations that use highly portable functional near-infrared spectroscopy (fNIRS) instruments to meet the demands of brain imaging experiments in low-resource environments and enable longitudinal investigations of brain function in the context of long-term malnutrition. However, recent studies in healthy subjects have demonstrated that high-density diffuse optical tomography (HD-DOT) can significantly improve image quality over that obtained with sparse fNIRS imaging arrays. In studies of both task activations and resting state functional connectivity, HD-DOT is beginning to approach the data quality of fMRI for superficial cortical regions. In this work, we developed a customized HD-DOT system for use in malnutrition studies in Cali, Colombia. Our results evaluate the performance of the HD-DOT instrument for assessing brain function in a cohort of malnourished children. In addition to demonstrating portability and wearability, we show the HD-DOT instrument\u27s sensitivity to distributed brain responses using a sensory processing task and measurements of homotopic functional connectivity. Task-evoked responses to the passive word listening task produce activations localized to bilateral superior temporal gyrus, replicating previously published work using this paradigm. Evaluating this localization performance across sparse and dense reconstruction schemes indicates that greater localization consistency is associated with a dense array of overlapping optical measurements. These results provide a foundation for additional avenues of investigation, including identifying and characterizing a child\u27s individual malnutrition burden and eventually contributing to intervention development

Mapping cortical activations underlying covert and overt language production using high-density diffuse optical tomography

Gold standard neuroimaging modalities such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and more recently electrocorticography (ECoG) have provided profound insights regarding the neural mechanisms underlying the processing of language, but they are limited in applications involving naturalistic language production especially in developing brains, during face-to-face dialogues, or as a brain-computer interface. High-density diffuse optical tomography (HD-DOT) provides high-fidelity mapping of human brain function with comparable spatial resolution to that of fMRI but in a silent and open scanning environment similar to real-life social scenarios. Therefore, HD-DOT has potential to be used in naturalistic settings where other neuroimaging modalities are limited. While HD-DOT has been previously validated against fMRI for mapping the neural correlates underlying language comprehension and covert (i.e., silent ) language production, HD-DOT has not yet been established for mapping the cortical responses to overt (i.e., out loud ) language production. In this study, we assessed the brain regions supporting a simple hierarchy of language tasks: silent reading of single words, covert production of verbs, and overt production of verbs in normal hearing right-handed native English speakers (n = 33). First, we found that HD-DOT brain mapping is resilient to movement associated with overt speaking. Second, we observed that HD-DOT is sensitive to key activations and deactivations in brain function underlying the perception and naturalistic production of language. Specifically, statistically significant results were observed that show recruitment of regions in occipital, temporal, motor, and prefrontal cortices across all three tasks after performing stringent cluster-extent based thresholding. Our findings lay the foundation for future HD-DOT studies of imaging naturalistic language comprehension and production during real-life social interactions and for broader applications such as presurgical language assessment and brain-machine interfaces

Decoding visual information from high-density diffuse optical tomography neuroimaging data

BACKGROUND: Neural decoding could be useful in many ways, from serving as a neuroscience research tool to providing a means of augmented communication for patients with neurological conditions. However, applications of decoding are currently constrained by the limitations of traditional neuroimaging modalities. Electrocorticography requires invasive neurosurgery, magnetic resonance imaging (MRI) is too cumbersome for uses like daily communication, and alternatives like functional near-infrared spectroscopy (fNIRS) offer poor image quality. High-density diffuse optical tomography (HD-DOT) is an emerging modality that uses denser optode arrays than fNIRS to combine logistical advantages of optical neuroimaging with enhanced image quality. Despite the resulting promise of HD-DOT for facilitating field applications of neuroimaging, decoding of brain activity as measured by HD-DOT has yet to be evaluated. OBJECTIVE: To assess the feasibility and performance of decoding with HD-DOT in visual cortex. METHODS AND RESULTS: To establish the feasibility of decoding at the single-trial level with HD-DOT, a template matching strategy was used to decode visual stimulus position. A receiver operating characteristic (ROC) analysis was used to quantify the sensitivity, specificity, and reproducibility of binary visual decoding. Mean areas under the curve (AUCs) greater than 0.97 across 10 imaging sessions in a highly sampled participant were observed. ROC analyses of decoding across 5 participants established both reproducibility in multiple individuals and the feasibility of inter-individual decoding (mean AUCs \u3e 0.7), although decoding performance varied between individuals. Phase-encoded checkerboard stimuli were used to assess more complex, non-binary decoding with HD-DOT. Across 3 highly sampled participants, the phase of a 60° wide checkerboard wedge rotating 10° per second through 360° was decoded with a within-participant error of 25.8±24.7°. Decoding between participants was also feasible based on permutation-based significance testing. CONCLUSIONS: Visual stimulus information can be decoded accurately, reproducibly, and across a range of detail (for both binary and non-binary outcomes) at the single-trial level (without needing to block-average test data) using HD-DOT data. These results lay the foundation for future studies of more complex decoding with HD-DOT and applications in clinical populations

Prefrontal cortex supports speech perception in listeners with cochlear implants

Cochlear implants are neuroprosthetic devices that can restore hearing in individuals with severe to profound hearing loss by electrically stimulating the auditory nerve. Because of physical limitations on the precision of this stimulation, the acoustic information delivered by a cochlear implant does not convey the same level of spectral detail as that conveyed by normal hearing. As a result, speech understanding in listeners with cochlear implants is typically poorer and more effortful than in listeners with normal hearing. The brain networks supporting speech understanding in listeners with cochlear implants are not well understood, partly due to difficulties obtaining functional neuroimaging data in this population. In the current study, we assessed the brain regions supporting spoken word understanding in adult listeners with right unilateral cochlear implants (n=20) and matched controls (n=18) using high-density diffuse optical tomography (HD-DOT), a quiet and non-invasive imaging modality with spatial resolution comparable to that of functional MRI. We found that while listening to spoken words in quiet, listeners with cochlear implants showed greater activity in the left dorsolateral prefrontal cortex, overlapping with functionally-defined processing seen in a spatial working memory task. These results suggest that listeners with cochlear implants require greater cognitive processing during speech understanding than listeners with normal hearing, supported by compensatory recruitment in the left dorsolateral prefrontal cortex