T1 Magnetic Resonance Imaging Head Segmentation for Diffuse Optical Tomography and Electroencephalography

Accurate segmentation of structural magnetic resonance images is critical for creating subject-specific forward models for functional neuroimaging source localization. In this work, we present an innovative segmentation algorithm that generates accurate head tissue layer thicknesses that are needed for diffuse optical tomography (DOT) data analysis. The presented algorithm is compared against other publicly available head segmentation methods. The proposed algorithm has a root mean square scalp thickness error of 1.60 mm, skull thickness error of 1.96 mm, and summed scalp and skull error of 1.49 mm. We also introduce a segmentation evaluation metric that evaluates the accuracy of tissue layer thicknesses in regions of the head where optodes are typically placed. The presented segmentation algorithm and evaluation metric are tools for improving the localization accuracy of neuroimaging with DOT, and also multimodal neuroimaging such as combined electroencephalography and DOT

The infant brain in the social world: Moving toward interactive social neuroscience with functional near-infrared spectroscopy

Typically developing infants rapidly acquire a sophisticated array of social skills within the first year of life. These social skills are largely learned within the context of day-to-day interactions with caregivers. While social neuroscience has made great gains in our knowledge of the underlying neural circuitry of social cognition and behavior, much of this work has focused on experiments that sacrifice ecological validity for experimental control. Functional near-infrared spectroscopy (fNIRS) is a promising methodology for measuring brain activity in the context of naturalistic social interactions. Here, we review what we have learned from fNIRS studies that have used traditional experimental stimuli to study social development during infancy. We then discuss recent infant fNIRS studies that have utilized more naturalistic social stimuli, followed by a discussion of applications of this methodology to the study of atypical social development, with a focus on infants at risk for autism spectrum disorder. We end with recommendations for applying fNIRS to studies of typically developing and at-risk infants in naturalistic social situations

Infants' neural responses to facial emotion in the prefrontal cortex are correlated with temperament: a functional near-infrared spectroscopy study

Accurate decoding of facial expressions is critical for human communication, particularly during infancy, before formal language has developed. Different facial emotions elicit distinct neural responses within the first months of life. However, there are broad individual differences in such responses, so that the same emotional expression can elicit different brain responses in different infants. In this study, we sought to investigate such differences in the processing of emotional faces by analyzing infants’s cortical metabolic responses to face stimuli and examining whether individual differences in these responses might vary as a function of infant temperament. Seven-month-old infants (N = 24) were shown photographs of women portraying happy expressions, and neural activity was recorded using functional near-infrared spectroscopy (fNIRS). Temperament data were collected using the Revised Infant Behavior Questionnaire Short Form, which assesses the broad temperament factors of Surgency/Extraversion (S/E), Negative Emotionality (NE), and Orienting/Regulation (O/R). We observed that oxyhemoglobin (oxyHb) responses to happy face stimuli were negatively correlated with infant temperament factors in channels over the left prefrontal cortex (uncorrected for multiple comparisons). To investigate the brain activity underlying this association, and to explore the use of fNIRS in measuring cortical asymmetry, we analyzed hemispheric asymmetry with respect to temperament groups. Results showed preferential activation of the left hemisphere in low-NE infants in response to smiling faces. These results suggest that individual differences in temperament are associated with differential prefrontal oxyHb responses to faces. Overall, these analyses contribute to our current understanding of face processing during infancy, demonstrate the use of fNIRS in measuring prefrontal asymmetry, and illuminate the neural correlates of face processing as modulated by temperament

Exploring the relation between brain response to speech at 6-months and language outcomes at 24-months in infants at high and low risk for autism spectrum disorder: a preliminary functional near-infrared spectroscopy study

Infants at high familial risk for autism spectrum disorder (ASD) are at increased risk for language impairments. Studies have demonstrated that atypical brain response to speech is related to language impairments in this population, but few have examined this relation longitudinally. We used functional near-infrared spectroscopy (fNIRS) to investigate the neural correlates of speech processing in 6-month-old infants at high (HRA) and low risk (LRA) for autism. We also assessed the relation between brain response to speech at 6-months and verbal developmental quotient (VDQ) scores at 24-months. LRA infants exhibited greater brain response to speech in bilateral anterior regions of interest (ROIs) compared to posterior ROIs, while HRA infants exhibited similar brain response across all ROIs. Compared to LRA infants, HRA+ infants who were later diagnosed with ASD had reduced brain response in bilateral anterior ROIs, while HRA- infants who were not later diagnosed with ASD had increased brain response in right posterior ROI. Greater brain response in left anterior ROI predicted VDQ scores for LRA infants only. Findings highlight the importance of studying HRA+ and HRA- infants separately, and implicate a different, more distributed neural system for speech processing in HRA infants that is not related to language functioning.Published versio

Measuring acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans using TD-fNIRS

Quantifying neural activity in natural conditions (i.e. conditions comparable to the standard clinical patient experience) during the administration of psychedelics may further our scientific understanding of the effects and mechanisms of action. This data may facilitate the discovery of novel biomarkers enabling more personalized treatments and improved patient outcomes. In this single-blind, placebo-controlled study with a non-randomized design, we use time-domain functional near-infrared spectroscopy (TD-fNIRS) to measure acute brain dynamics after intramuscular subanesthetic ketamine (0.75 mg/kg) and placebo (saline) administration in healthy participants (n = 15, 8 females, 7 males, age 32.4 ± 7.5 years) in a clinical setting. We found that the ketamine administration caused an altered state of consciousness and changes in systemic physiology (e.g. increase in pulse rate and electrodermal activity). Furthermore, ketamine led to a brain-wide reduction in the fractional amplitude of low frequency fluctuations, and a decrease in the global brain connectivity of the prefrontal region. Lastly, we provide preliminary evidence that a combination of neural and physiological metrics may serve as predictors of subjective mystical experiences and reductions in depressive symptomatology. Overall, our study demonstrated the successful application of fNIRS neuroimaging to study the physiological effects of the psychoactive substance ketamine in humans, and can be regarded as an important step toward larger scale clinical fNIRS studies that can quantify the impact of psychedelics on the brain in standard clinical settings

Acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans: A TD-fNIRS neuroimaging study

Quantifying neural activity in natural conditions (i.e. conditions comparable to the standard clinical patient experience) during the administration of psychedelics may further our scientific understanding of the effects and mechanisms of action. This data may facilitate the discovery of novel biomarkers enabling more personalized treatments and improved patient outcomes. In this single-blind, placebo-controlled study with a non-randomized design, we use time-domain functional near-infrared spectroscopy (TD-fNIRS) to measure acute brain dynamics after intramuscular subanesthetic ketamine (0.75 mg/kg) and placebo (saline) administration in healthy participants (n= 15, 8 females, 7 males, age 32.4 ± 7.5 years) in a clinical setting. We found that the ketamine administration caused an altered state of consciousness and changes in systemic physiology (e.g. increase in pulse rate and electrodermal activity). Furthermore, ketamine led to a brain-wide reduction in the fractional amplitude of low frequency fluctuations (fALFF), and a decrease in the global brain connectivity of the prefrontal region. Lastly, we provide preliminary evidence that a combination of neural and physiological metrics may serve as predictors of subjective mystical experiences and reductions in depressive symptomatology. Overall, our studies demonstrated the successful application of fNIRS neuroimaging to study the physiological effects of the psychoactive substance ketamine and can be regarded as an important step toward larger scale clinical fNIRS studies that can quantify the impact of psychedelics on the brain in standard clinical settings

Kernel Flow:a high channel count scalable time-domain functional near-infrared spectroscopy system

Significance: Time-domain functional near-infrared spectroscopy (TD-fNIRS) has been considered as the gold standard of noninvasive optical brain imaging devices. However, due to the high cost, complexity, and large form factor, it has not been as widely adopted as continuous wave NIRS systems. Aim: Kernel Flow is a TD-fNIRS system that has been designed to break through these limitations by maintaining the performance of a research grade TD-fNIRS system while integrating all of the components into a small modular device. Approach: The Kernel Flow modules are built around miniaturized laser drivers, custom integrated circuits, and specialized detectors. The modules can be assembled into a system with dense channel coverage over the entire head. Results: We show performance similar to benchtop systems with our miniaturized device as characterized by standardized tissue and optical phantom protocols for TD-fNIRS and human neuroscience results. Conclusions: The miniaturized design of the Kernel Flow system allows for broader applications of TD-fNIRS.</p

A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation.

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies