White matter trajectories over the lifespan.

White matter (WM) changes occur throughout the lifespan at a different rate for each developmental period. We aggregated 10879 structural MRIs and 6186 diffusion-weighted MRIs from participants between 2 weeks to 100 years of age. Age-related changes in gray matter and WM partial volumes and microstructural WM properties, both brain-wide and on 29 reconstructed tracts, were investigated as a function of biological sex and hemisphere, when appropriate. We investigated the curve fit that would best explain age-related differences by fitting linear, cubic, quadratic, and exponential models to macro and microstructural WM properties. Following the first steep increase in WM volume during infancy and childhood, the rate of development slows down in adulthood and decreases with aging. Similarly, microstructural properties of WM, particularly fractional anisotropy (FA) and mean diffusivity (MD), follow independent rates of change across the lifespan. The overall increase in FA and decrease in MD are modulated by demographic factors, such as the participant's age, and show different hemispheric asymmetries in some association tracts reconstructed via probabilistic tractography. All changes in WM macro and microstructure seem to follow nonlinear trajectories, which also differ based on the considered metric. Exponential changes occurred for the WM volume and FA and MD values in the first five years of life. Collectively, these results provide novel insight into how changes in different metrics of WM occur when a lifespan approach is considered.

Infant sustained attention differs by context and social content in the first 2 years of life.

Sustained attention (SA) is an endogenous form of attention that emerges in infancy and reflects cognitive engagement and processing. SA is critical for learning and has been measured using different methods during screen-based and interactive contexts involving social and nonsocial stimuli. How SA differs by measurement method, context, and stimuli across development in infancy is not fully understood. This 2-year longitudinal study examines attention using one measure of overall looking behavior and three measures of SA-mean look duration, percent time in heart rate-defined SA, and heart rate change during SA-in N = 53 infants from 1 to 24 months across four unique task conditions: social videos, nonsocial videos, social interactions (face-to-face play), and nonsocial interactions (toy engagement). Results suggest that developmental changes in attention differ by measurement method, task context (screen or interaction), and task stimulus (social or nonsocial). During social interactions, overall looking and look durations declined after age 3-4 months, whereas heart rate-defined attention measures remained stable. All SA measures were greater for videos than for live interaction conditions throughout the first 6 months, but SA to social and nonsocial stimuli within each task context were equivalent. In the second year of life, SA measured with look durations was greater for social videos compared to other conditions, heart rate-defined SA was greater for social videos compared to nonsocial interactions, and heart rate change during SA was similar across conditions. Together, these results suggest that different measures of attention to social and nonsocial stimuli may reflect unique developmental processes and are important to compare and consider together, particularly when using infant attention as a marker of typical or atypical development. RESEARCH HIGHLIGHTS: Attention measure, context, and social content uniquely differentiate developmental trajectories of attention in the first 2 years of life. Overall looking to caregivers during dyadic social interactions declines significantly from 4 to 6 months of age while sustained attention (SA) to caregivers remains stable. Heart rate-defined SA generally differentiates stimulus context where infants show greater SA while watching videos than while engaging with toys.

Neural correlates of face processing among preschoolers with fragile X syndrome, autism spectrum disorder, autism siblings, and typical development.

The current study examined patterns of event-related potential (ERP) responses during a face processing task in groups of preschoolers uniquely impacted by autism spectrum disorder (ASD), including (1) children with ASD; (2) children with fragile X syndrome (FXS); (3) children with familial risk for ASD, but without a diagnosis (i.e., ASIBs); and (4) a low-risk control (LRC) group. Children with FXS have a high incidence of ASD diagnoses, but there have been no studies of the ERP response to faces in children with FXS and little work focused on children with ASD who have cognitive impairment. The current study examined children's ERP responses to faces and houses in four groups: LRC (N = 28, age = 5.2 years), ASIB (N = 23, age = 5.5 years), FXS (N = 19, age = 5.82 years), and ASD (N = 23, age = 5.5 years). The FXS and ASD groups were characterized by the presence of cognitive impairment. Pictures of upright and inverted faces and houses were presented while recording EEG with a 128-channel system. The N170 occurred at about 200 ms post stimulus onset, was largest on the posterior-lateral electrodes, and was larger for faces than houses. The P1 and N170 ERP components were larger for the FXS group than for the other three groups. The N170 ERP amplitude for the ASD and ASIB groups was smaller than both the LRC and FXS groups, and the LRC and FXS groups had the largest N170 responses on the right side. No difference was found in N170 latency between groups. The similarity of the ASD and ASIB responses suggest a common genetic or environmental origin of the reduced response. Although children with FXS have a high incidence of ASD outcomes, they differed from ASD and ASIB children in this study. Specifically, the children with FXS were hyperresponsive to all stimulus types while the ASD and ASIB groups showed attenuated responses for specific stimuli.

Multimodal study of the neural sources of error monitoring in adolescents and adults.

The ability to monitor performance during a goal-directed behavior differs among children and adults in ways that can be measured with several tasks and techniques. As well, recent work has shown that individual differences in error monitoring moderate temperamental risk for anxiety and that this moderation changes with age. We investigated age differences in neural responses linked to performance monitoring using a multimodal approach. The approach combined functional MRI and source localization of event-related potentials (ERPs) in 12-year-old, 15-year-old, and adult participants. Neural generators of two components related to performance and error monitoring, the N2 and ERN, lay within specific areas of fMRI clusters. Whereas correlates of the N2 component appeared similar across age groups, age-related differences manifested in the location of the generators of the ERN component. The dorsal anterior cingulate cortex (dACC) was the predominant source location for the 12-year-old group; this area manifested posteriorly for the 15-year-old and adult groups. A fMRI-based ROI analysis confirmed this pattern of activity. These results suggest that changes in the underlying neural mechanisms are related to developmental changes in performance monitoring.

Frontal asymmetry assessed in infancy using functional near-infrared spectroscopy is associated with emotional and behavioral problems in early childhood.

Frontal asymmetry (FA), the difference in brain activity between the left versus right frontal areas, is thought to reflect approach versus avoidance motivation. This study (2012-2021) used functional near-infrared spectroscopy to investigate if infant (Mage  = 7.63 months; N = 90; n = 48 male; n = 75 White) FA in the dorsolateral prefrontal cortex relates to psychopathology in later childhood (Mage  = 62.05 months). Greater right FA to happy faces was associated with increased internalizing (η2  = .09) and externalizing (η2  = .06) problems at age 5 years. Greater right FA to both happy and fearful faces was associated with an increased likelihood of a lifetime anxiety diagnosis (R2 > .13). FA may be an informative and early-emerging marker for psychopathology.

Cortical Source Analysis of the Face Sensitive N290 ERP Component in Infants at High Risk for Autism.

Appropriate head models for cortical source analysis were investigated and applied to source analyses examining the neural bases of the face-sensitive N290 event-related potential (ERP) component in infants at high risk for autism spectrum disorder (ASD). This included infant siblings of children with ASD (ASIBs) and infants with fragile X syndrome (FXS). First, alternative head models for use with ASIBs and FXS were investigated. Head models created from the infant's own MRI were examined in relation to five head models based on average MRI templates. The results of the head model comparison identified group-specific (i.e., ASIB or FXS) head models created from a large collection of structural MRIs as the best substitution for the head model created from the participant's own structural MRI. Second, the cortical source analysis was completed on N290 data collected from a previous study to investigate brain areas associated with face sensitive ERP responses. Participants' own MRIs were used for head models when available, and the group-specific head model was used when the participants' own MRIs were not available. The results provide evidence for unique patterns of neural activation during face processing across infants at high and low risk for ASD and across etiologically distinct high-risk groups. All infants demonstrated greater activation to faces than toys in brain areas most associated with specialized face processing. Infants with FXS displayed higher levels of activation to faces across all areas analyzed, while ASIBs show more muted levels of activation. Overall, the results of the current study demonstrate the importance of group-specific head models for accurate cortical source analysis in infants at high risk for ASD. This also allows for further research on early distinctions in brain function based on risk status.

Age-related changes in diffuse optical tomography sensitivity profiles from childhood to adulthood.

SIGNIFICANCE: Diffuse optical tomography (DOT) uses near-infrared light spectroscopy to measure changes in cerebral hemoglobin concentration. Anatomical interpretations of the brain location that generates the hemodynamic signal require accurate descriptions of the DOT sensitivity to the underlying cortex. DOT sensitivity profiles are different in infants compared with adults. However, the descriptions of DOT sensitivity profiles from early childhood to adulthood are lacking despite the continuous head and brain development. AIM: We aim to investigate age-related differences in DOT sensitivity profiles in individuals aged from 2 to 34 years with narrow age ranges of 0.5 or 1 year. APPROACH: We implemented existing photon migration simulation methods and computed source-detector channel DOT sensitivity using age-appropriate, realistic head models. RESULTS: DOT sensitivity profiles change systematically as a function of source-detector separation distance for all age groups. Children displayed distinctive DOT sensitivity profiles compared to older individuals, and the differences were enhanced at larger separation distances. CONCLUSIONS: The findings have important implications for the design of source-detector placement and image reconstruction. Age-appropriate realistic head models should be used to provide anatomical guidance for standalone DOT data. Using age-inappropriate head models will have more negative impacts on estimation accuracy in younger children.

Association of psychosocial adversity and social information processing in children raised in a low-resource setting: an fNIRS study.

Social cognition skills and socioemotional development are compromised in children growing up in low SES contexts, however, the mechanisms underlying this association remain unknown. Exposure to psychosocial risk factors early in life alters the child's social milieu and in turn, could lead to atypical processing of social stimuli. In this study, we used functional Near Infrared Spectroscopy (fNIRS) to measure cortical responses to a social discrimination task in children raised in a low-resource setting at 6, 24, and 36 months. In addition, we assessed the relation between cortical responses to social and non-social information with psychosocial risk factors assessed using the Childhood Psychosocial Adversity Scale (CPAS). In line with previous findings, we observed specialization to social stimuli in cortical regions in all age groups. In addition, we found that risk factors were associated with social discrimination at 24 months (intimate partner violence and verbal abuse and family conflict) and 36 months (verbal abuse and family conflict and maternal depression) but not at 6 months. Overall, the results show that exposure to psychosocial adversity has more impact on social information processing in toddlerhood than earlier in infancy.

Evaluating Head Models for Cortical Source Localization of the Face-Sensitive N290 Component in Infants.

Accurate cortical source localization of event-related potentials (ERPs) requires using realistic head models constructed from the participant's structural magnetic resonance imaging (MRI). A challenge in developmental studies is the limited accessibility of participant-specific MRIs. The present study compared source localization of infants' N290 ERP activities estimated using participant-specific head models with a series of substitute head models. The N290 responses to faces relative to toys were measured in 36 infants aged at 4.5, 7.5, 9, and 12 months. The substitutes were individual-based head models constructed from age-matched MRIs with closely matched ("close") or different ("far") head measures with the participants, age-appropriate average template, and age-inappropriate average templates. The greater source responses to faces than toys at the middle fusiform gyrus (mFG) estimated using participant-specific head models were preserved in individual-based head models, but not average templates. The "close" head models yielded the best fit with the participant-specific head models in source activities at the mFG and across face-processing-related regions of interest (ROIs). The age-appropriate average template showed mixed results, not supporting the stimulus effect but showed topographical distributions across the ROIs like the participant-specific head models. The "close" head models are the most optimal substitute for participant-specific MRIs.

Cortical Source Analysis of Event-Related Potentials: A Developmental Approach.

Cortical source analysis of electroencephalographic (EEG) signals has become an important tool in the analysis of brain activity. The aim of source analysis is to reconstruct the cortical generators (sources) of the EEG signal recorded on the scalp. The quality of the source reconstruction relies on the accuracy of the forward problem, and consequently the inverse problem. An accurate forward solution is obtained when an appropriate imaging modality (i.e., structural magnetic resonance imaging - MRI) is used to describe the head geometry, precise electrode locations are identified with 3D maps of the sensor positions on the scalp, and realistic conductivity values are determined for each tissue type of the head model. Together these parameters contribute to the definition of realistic head models. Here, we describe the steps necessary to reconstruct the cortical generators of the EEG signal recorded on the scalp. We provide an example of source reconstruction of event-related potentials (ERPs) during a face-processing task performed by a 6-month-old infant. We discuss the adjustments necessary to perform source analysis with measures different from the ERPs. The proposed pipeline can be applied to the investigation of different cognitive tasks in both younger and older participants.

Neural correlates of inhibitory control and associations with cognitive outcomes in Bangladeshi children exposed to early adversities.

There is strong support for the view that children growing up in low-income homes typically evince poorer performance on tests of inhibitory control compared to those growing up in higher income homes. Unfortunately, the vast majority of the work documenting this association has been conducted in high-income countries. It is not yet known whether the mechanisms found to mediate this association would generalize to children in low- and middle-income countries, where the risks of exposure to extreme poverty and a wide range of both biological and psychosocial hazards may be greater. We examined relations among early adversity, neural correlates of inhibitory control, and cognitive outcomes in 154 5-year-old children living in Dhaka, Bangladesh, an area with a high prevalence of poverty. Participants completed a go/no-go task assessing inhibitory control and their behavioral and event-related potential responses were assessed. Cortical source analysis was performed. We collected measures of poverty, malnutrition, maternal mental health, psychosocial adversity, and cognitive skills. Supporting studies in high-income countries, children in this sample exhibited a longer N2 latency and higher P3 amplitude to the no-go versus go condition. Unexpectedly, children had a more pronounced N2 amplitude during go trials than no-go trials. The N2 latency was related to their behavioral accuracy on the go/no-go task. The P3 mean amplitude, behavioral accuracy, and reaction time during the task were all associated with intelligence-quotient (IQ) scores. Children who experienced higher levels of psychosocial adversity had lower accuracy on the task and lower IQ scores.

Neural Correlates of Infant Face Processing and Later Emerging Autism Symptoms in Fragile X Syndrome.

Fragile X syndrome (FXS) is the leading known genetic cause of autism spectrum disorder (ASD) with 60-74% of males with FXS meeting diagnostic criteria for ASD. Infants with FXS have demonstrated atypical neural responses during face processing that are unique from both typically developing, low-risk infants and infants at high familial risk for ASD (i.e., infants siblings of children with ASD). In the current study, event-related potential (ERP) responses during face processing measured at 12 months of age were examined in relation to ASD symptoms measured at ~48 months of age in participants with FXS, as well as siblings of children with ASD and low-risk control participants. Results revealed that greater amplitude N290 responses in infancy were associated with more severe ASD symptoms in childhood in FXS and in siblings of children with ASD. This pattern of results was not observed for low-risk control participants. Reduced Nc amplitude was associated with more severe ASD symptoms in participants with FXS but was not observed in the other groups. This is the first study to examine ASD symptoms in childhood in relation to infant ERP responses in FXS. Results indicate that infant ERP responses may be predictive of later symptoms of ASD in FXS and the presence of both common and unique pathways to ASD in etiologically-distinct high-risk groups is supported (i.e., syndromic risk vs. familial risk).

devfOLD: a toolbox for designing age-specific fNIRS channel placement.

Significance: Near-infrared spectroscopy (NIRS) is a noninvasive technique that uses scalp-placed sensors to measure cerebral hemoglobin concentration. Commercial NIRS instruments do not allow for whole-head coverage and do not intrinsically indicate which brain areas generate the NIRS signal. Hence, the challenge is to design source-detector channel arrangement that maximizes sensitivity to a given brain region of interest (ROI). Existing methods for optimizing channel placement design have been developed using adult head models. Thus, they have limited utility for developmental research. Aim: We aim to build an application from an existing toolbox (fOLD) that guides NIRS channel configuration based on age group, stereotaxic atlas, and ROI (devfOLD). Approach: The devfOLD provides NIRS channel-to-ROI specificity computed using photon propagation simulation with realistic head models from infant, child, and adult age groups. Results: Cortical locations and user-specified specificity cut-off values influence the between-age consistency and differences in the ROI-to-channel correspondence among the example infant and adult age groups. Conclusions: The study highlights the importance of incorporating age-specific head models for optimizing NIRS channel configurations. The devfOLD toolbox is publicly shared and compatible with multiple operating systems.

A single-session behavioral protocol for successful event-related potential recording in children with neurodevelopmental disorders.

Event-related potentials (ERPs) are an ideal tool for measuring neural responses in a wide range of participants, including children diagnosed with neurodevelopmental disorders (NDDs). However, due to perceived barriers regarding participant compliance, much of this work has excluded children with low IQ and/or reduced adaptive functioning, significant anxiety symptoms, and/or sensory processing difficulties, including heterogeneous samples of children with autism spectrum disorder (ASD) and children with fragile X syndrome (FXS). We have developed a behavioral support protocol designed to obtain high-quality ERP data from children in a single session. Using this approach, ERP data were successfully collected from participants with ASD, FXS, and typical development (TD). Higher success rates were observed for children with ASD and TD than children with FXS. Unique clinical-behavioral characteristics were associated with successful data collection across these groups. Higher chronological age, nonverbal mental age, and receptive language skills were associated with a greater number of valid trials completed in children with ASD. In contrast, higher language ability, lower autism severity, increased anxiety, and increased sensory hyperresponsivity were associated with a greater number of valid trials completed in children with FXS. This work indicates that a "one-size-fits-all" approach cannot be taken to ERP research on children with NDDs, but that a single-session paradigm is feasible and is intended to promote increased representation of children with NDDs in neuroscience research through development of ERP methods that support inclusion of diverse and representative samples.

Peak selection and latency jitter correction in developmental event-related potentials.

Event-related potentials (ERPs) provide great insight into neural responses, yet developmental ERP work is plagued with inconsistent approaches to identifying and quantifying component latency. In this analytical review, we describe popular conventions for the selection of time windows for ERP analysis and assert that a data-driven strategy should be applied to the identification of component latency within individual participants' data. This may overcome weaknesses of more general approaches to peak selection; however, it does not account for trial-by-trial variability within a participant. This issue, known as ERP latency jitter, may blur the average ERP, misleading the interpretation of neural mechanisms. Recently, the ReSync MATLAB toolbox has been made available for correction of latency jitter. Although not created specifically for pediatric ERP data, this approach can be adapted for developmental researchers. We have demonstrated the use of the ReSync toolbox with individual infant and child datasets to illustrate its utility. Details about our peak detection script and the ReSync toolbox are provided. The adoption of data processing procedures that allow for accurate, study-specific component selection and reduce trial-by-trial asynchrony strengthens developmental ERP research by decreasing noise included in ERP analyses and improving the representation of the neural response.

The Influence of the Head Model Conductor on the Source Localization of Auditory Evoked Potentials.

The accuracy of EEG source analysis reconstruction improves when a realistic head volume conductor is modeled. In this study we investigated how the progressively more complex head representations influence the spatial localization of auditory-evoked potentials (AEPs). Fourteen young-adult participants with normal hearing performed the AEP task. Individualized head models were obtained from structural MRI and diffusion-weighted imaging scans collected in a separate session. AEPs were elicited by 1 k Hz and 4 k Hz tone bursts during a passive-listening tetanizing paradigm. We compared the amplitude of the N1 and P2 components before and after 4 min of tetanic-stimulation with 1 k Hz sounds. Current density reconstruction values of both components were investigated in the primary auditory cortex and adjacent areas. Furthermore, we compared the signal topography and magnitude obtained with 10 different head models on the EEG forward solution. Starting from the simplest model (scalp, skull, brain), we investigated the influence of modeling the CSF, distinguishing between GM and WM conductors, and including anisotropic WM values. We localized the activity of AEPs within the primary auditory cortex, but not in adjacent areas. The inclusion of the CSF compartment had the strongest influence on the source reconstruction, whereas white matter anisotropy led to a smaller improvement. We conclude that individualized realistic head models provide the best solution for the forward solution when modeling the CSF conductor.

Investigating developmental changes in scalp-to-cortex correspondence using diffuse optical tomography sensitivity in infancy.

Significance: Diffuse optical tomography (DOT) uses near-infrared light spectroscopy (NIRS) to measure changes in cerebral hemoglobin concentration. Anatomical interpretations of NIRS data require accurate descriptions of the cranio-cerebral relations and DOT sensitivity to the underlying cortical structures. Such information is limited for pediatric populations because they undergo rapid head and brain development. Aim: We aim to investigate age-related differences in scalp-to-cortex distance and mapping between scalp locations and cortical regions of interest (ROIs) among infants (2 weeks to 24 months with narrow age bins), children (4 and 12 years), and adults (20 to 24 years). Approach: We used spatial scalp projection and photon propagation simulation methods with age-matched realistic head models based on MRIs. Results: There were age-group differences in the scalp-to-cortex distances in infancy. The developmental increase was magnified in children and adults. There were systematic age-related differences in the probabilistic mappings between scalp locations and cortical ROIs. Conclusions: Our findings have important implications in the design of sensor placement and making anatomical interpretations in NIRS and fNIRS research. Age-appropriate, realistic head models should be used to provide anatomical guidance for standalone DOT data in infants.

Age-related changes in diffuse optical tomography sensitivity profiles in infancy.

Diffuse optical tomography uses near-infrared light spectroscopy to measure changes in cerebral hemoglobin concentration. Anatomical interpretations of the location that generates the hemodynamic signal requires accurate descriptions of diffuse optical tomography sensitivity to the underlying cortical structures. Such information is limited for pediatric populations because they undergo rapid head and brain development. The present study used photon propagation simulation methods to examine diffuse optical tomography sensitivity profiles in realistic head models among infants ranging from 2 weeks to 24 months with narrow age bins, children (4 and 12 years) and adults (20 to 24 years). The sensitivity profiles changed systematically with the source-detector separation distance. The peak of the sensitivity function in the head was largest at the smallest separation distance and decreased as separation distance increased. The fluence value dissipated more quickly with sampling depth at the shorter source-detector separations than the longer separation distances. There were age-related differences in the shape and variance of sensitivity profiles across a wide range of source-detector separation distances. Our findings have important implications in the design of sensor placement and diffuse optical tomography image reconstruction in (functional) near-infrared light spectroscopy research. Age-appropriate realistic head models should be used to provide anatomical guidance for standalone near-infrared light spectroscopy data in infants.

Structural templates for imaging EEG cortical sources in infants.

Electroencephalographic (EEG) source reconstruction is a powerful approach that allows anatomical localization of electrophysiological brain activity. Algorithms used to estimate cortical sources require an anatomical model of the head and the brain, generally reconstructed using magnetic resonance imaging (MRI). When such scans are unavailable, a population average can be used for adults, but no average surface template is available for cortical source imaging in infants. To address this issue, we introduce a new series of 13 anatomical models for subjects between zero and 24 months of age. These templates are built from MRI averages and boundary element method (BEM) segmentation of head tissues available as part of the Neurodevelopmental MRI Database. Surfaces separating the pia mater, the gray matter, and the white matter were estimated using the Infant FreeSurfer pipeline. The surface of the skin as well as the outer and inner skull surfaces were extracted using a cube marching algorithm followed by Laplacian smoothing and mesh decimation. We post-processed these meshes to correct topological errors and ensure watertight meshes. Source reconstruction with these templates is demonstrated and validated using 100 high-density EEG recordings from 7-month-old infants. Hopefully, these templates will support future studies on EEG-based neuroimaging and functional connectivity in healthy infants as well as in clinical pediatric populations.

Neural responses to happy, fearful and angry faces of varying identities in 5- and 7-month-old infants.

The processing of facial emotion is an important social skill that develops throughout infancy and early childhood. Here we investigate the neural underpinnings of the ability to process facial emotion across changes in facial identity in cross-sectional groups of 5- and 7-month-old infants. We simultaneously measured neural metabolic, behavioral, and autonomic responses to happy, fearful, and angry faces of different female models using functional near-infrared spectroscopy (fNIRS), eye-tracking, and heart rate measures. We observed significant neural activation to these facial emotions in a distributed set of frontal and temporal brain regions, and longer looking to the mouth region of angry faces compared to happy and fearful faces. No differences in looking behavior or neural activations were observed between 5- and 7-month-olds, although several exploratory, age-independent associations between neural activations and looking behavior were noted. Overall, these findings suggest more developmental stability than previously thought in responses to emotional facial expressions of varying identities between 5- and 7-months of age.