Mapping brain function in adults and young children during naturalistic viewing with high-density diffuse optical tomography.

Human studies of early brain development have been limited by extant neuroimaging methods. MRI scanners present logistical challenges for imaging young children, while alternative modalities like functional near-infrared spectroscopy have traditionally been limited by image quality due to sparse sampling. In addition, conventional tasks for brain mapping elicit low task engagement, high head motion, and considerable participant attrition in pediatric populations. As a result, typical and atypical developmental trajectories of processes such as language acquisition remain understudied during sensitive periods over the first years of life. We evaluate high-density diffuse optical tomography (HD-DOT) imaging combined with movie stimuli for high resolution optical neuroimaging in awake children ranging from 1 to 7 years of age. We built an HD-DOT system with design features geared towards enhancing both image quality and child comfort. Furthermore, we characterized a library of animated movie clips as a stimulus set for brain mapping and we optimized associated data analysis pipelines. Together, these tools could map cortical responses to movies and contained features such as speech in both adults and awake young children. This study lays the groundwork for future research to investigate response variability in larger pediatric samples and atypical trajectories of early brain development in clinical populations.

Identifying Naturalistic Movies from Human Brain Activity with High-Density Diffuse Optical Tomography.

Modern neuroimaging modalities, particularly functional MRI (fMRI), can decode detailed human experiences. Thousands of viewed images can be identified or classified, and sentences can be reconstructed. Decoding paradigms often leverage encoding models that reduce the stimulus space into a smaller yet generalizable feature set. However, the neuroimaging devices used for detailed decoding are non-portable, like fMRI, or invasive, like electrocorticography, excluding application in naturalistic use. Wearable, non-invasive, but lower-resolution devices such as electroencephalography and functional near-infrared spectroscopy (fNIRS) have been limited to decoding between stimuli used during training. Herein we develop and evaluate model-based decoding with high-density diffuse optical tomography (HD-DOT), a higher-resolution expansion of fNIRS with demonstrated promise as a surrogate for fMRI. Using a motion energy model of visual content, we decoded the identities of novel movie clips outside the training set with accuracy far above chance for single-trial decoding. Decoding was robust to modulations of testing time window, different training and test imaging sessions, hemodynamic contrast, and optode array density. Our results suggest that HD-DOT can translate detailed decoding into naturalistic use.

Ultra-high density imaging arrays for diffuse optical tomography of human brain improve resolution, signal-to-noise, and information decoding.

Functional magnetic resonance imaging (fMRI) has dramatically advanced non-invasive human brain mapping and decoding. Functional near-infrared spectroscopy (fNIRS) and high-density diffuse optical tomography (HD-DOT) non-invasively measure blood oxygen fluctuations related to brain activity, like fMRI, at the brain surface, using more-lightweight equipment that circumvents ergonomic and logistical limitations of fMRI. HD-DOT grids have smaller inter-optode spacing (∼13 mm) than sparse fNIRS (∼30 mm) and therefore provide higher image quality, with spatial resolution ∼1/2 that of fMRI. Herein, simulations indicated reducing inter-optode spacing to 6.5 mm would further improve image quality and noise-resolution tradeoff, with diminishing returns below 6.5 mm. We then constructed an ultra-high-density DOT system (6.5-mm spacing) with 140 dB dynamic range that imaged stimulus-evoked activations with 30-50% higher spatial resolution and repeatable multi-focal activity with excellent agreement with participant-matched fMRI. Further, this system decoded visual stimulus position with 19-35% lower error than previous HD-DOT, throughout occipital cortex.

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 > 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.

Structured illumination diffuse optical tomography for noninvasive functional neuroimaging in mice.

Optical intrinsic signal (OIS) imaging has been a powerful tool for capturing functional brain hemodynamics in rodents. Recent wide field-of-view implementations of OIS have provided efficient maps of functional connectivity from spontaneous brain activity in mice. However, OIS requires scalp retraction and is limited to superficial cortical tissues. Diffuse optical tomography (DOT) techniques provide noninvasive imaging, but previous DOT systems for rodent neuroimaging have been limited either by sparse spatial sampling or by slow speed. Here, we develop a DOT system with asymmetric source-detector sampling that combines the high-density spatial sampling (0.4 mm) detection of a scientific complementary metal-oxide-semiconductor camera with the rapid (2 Hz) imaging of a few ([Formula: see text]) structured illumination (SI) patterns. Analysis techniques are developed to take advantage of the system's flexibility and optimize trade-offs among spatial sampling, imaging speed, and signal-to-noise ratio. An effective source-detector separation for the SI patterns was developed and compared with light intensity for a quantitative assessment of data quality. The light fall-off versus effective distance was also used for in situ empirical optimization of our light model. We demonstrated the feasibility of this technique by noninvasively mapping the functional response in the somatosensory cortex of the mouse following electrical stimulation of the forepaw.