The importance of decomposing periodic and aperiodic EEG signals for assessment of brain function in a global context.

Measures of early neuro-cognitive development that are suitable for use in low-resource settings are needed to enable studies of the effects of early adversity on the developing brain in a global context. These measures should have high acquisition rates and good face and construct validity. Here, we investigated the feasibility of a naturalistic electroencephalography (EEG) paradigm in a low-resource context during childhood. Additionally, we examined the sensitivity of periodic and aperiodic EEG metrics to social and non-social stimuli. We recorded simultaneous 20-channel EEG and eye-tracking in 72 children aged 4-12 years (45 females) while they watched videos of women singing nursery rhymes and moving toys, selected to represent familiar childhood experiences. These measures were part of a feasibility study that assessed the feasibility and acceptability of a follow-up data collection of the South African Safe Passage Study, which tracks environmental adversity and brain and cognitive development from before birth up until childhood. We examined whether data quantity and quality varied with child characteristics and the sensitivity of varying EEG metrics (canonical band power in the theta and alpha band and periodic and aperiodic features of the power spectra). We found that children who completed the EEG and eye-tracking assessment were, in general, representative of the full cohort. Data quantity was higher in children with greater visual attention to the stimuli. Out of the tested EEG metrics, periodic measures in the theta frequency range were most sensitive to condition differences, compared to alpha range measures and canonical and aperiodic EEG measures. Our results show that measuring EEG during ecologically valid social and non-social stimuli is feasible in low-resource settings, is feasible for most children, and produces robust indices of social brain function. This work provides preliminary support for testing longitudinal links between social brain function, environmental factors, and emerging behaviors.

Neuroadaptive Bayesian optimisation can allow integrative design spaces at the individual level in the social and behavioural sciences and beyond.

Almaatouq et al. propose an integrative experiment design space combined with large samples for scientific advancement. We argue recent innovative designs combining closed-loop experiment designs and Bayesian optimisation allow for integrative experiments at an individual level during a single session, circumventing the necessity for large samples. This method can be applied across disciplines, including developmental and clinical research.

Real-time monitoring of infant theta power during naturalistic social experiences.

Infant-directed speech and direct gaze are important social cues that shape infant's attention to their parents. Traditional methods for probing their effect on infant attention involve a small number of pre-selected screen-based stimuli, which do not capture the complexity of real-world interactions. Here, we used neuroadaptive Bayesian Optimization (NBO) to search a large 'space' of different naturalistic social experiences that systematically varied in their visual (gaze direct to averted) and auditory properties (infant directed speech to nonvocal sounds). We measured oscillatory brain responses (relative theta power) during episodes of naturalistic social experiences in 57 typically developing 6- to 12-month-old infants. Relative theta power was used as input to the NBO algorithm to identify the naturalistic social context that maximally elicited attention in each individual infant. Results showed that individual infants were heterogeneous in the stimulus that elicited maximal theta with no overall stronger attention for direct gaze or infant-directed speech; however, individual differences in attention towards averted gaze were related to interpersonal skills and greater likelihood of preferring speech and direct gaze was observed in infants whose parents showed more positive affect. Our work indicates NBO may be a fruitful method for probing the role of distinct social cues in eliciting attention in naturalistic social contexts at the individual level.

Modulation of EEG theta by naturalistic social content is not altered in infants with family history of autism.

Theta oscillations (spectral power and connectivity) are sensitive to the social content of an experience in typically developing infants, providing a possible marker of early social brain development. Autism is a neurodevelopmental condition affecting early social behaviour, but links to underlying social brain function remain unclear. We explored whether modulations of theta spectral power and connectivity by naturalistic social content in infancy are related to family history for autism. Fourteen-month-old infants with (family history; FH; N = 75) and without (no family history; NFH; N = 26) a first-degree relative with autism watched social and non-social videos during EEG recording. We calculated theta (4-5 Hz) spectral power and connectivity modulations (social-non-social) and associated them with outcomes at 36 months. We replicated previous findings of increased theta power and connectivity during social compared to non-social videos. Theta modulations with social content were similar between groups, for both power and connectivity. Together, these findings suggest that neural responses to naturalistic social stimuli may not be strongly altered in 14-month-old infants with family history of autism.

Qualitative differences in the spatiotemporal brain states supporting configural face processing emerge in adolescence in autism.

BACKGROUND: Studying the neural processing of faces can illuminate the mechanisms of compromised social expertise in autism. To resolve a longstanding debate, we examined whether differences in configural face processing in autism are underpinned by quantitative differences in the activation of typical face processing pathways, or the recruitment of non-typical neural systems. METHODS: We investigated spatial and temporal characteristics of event-related EEG responses to upright and inverted faces in a large sample of children, adolescents, and adults with and without autism. We examined topographic analyses of variance and global field power to identify group differences in the spatial and temporal response to face inversion. We then examined how quasi-stable spatiotemporal profiles - microstates - are modulated by face orientation and diagnostic group. RESULTS: Upright and inverted faces produced distinct profiles of topography and strength in the topographical analyses. These topographical profiles differed between diagnostic groups in adolescents, but not in children or adults. In the microstate analysis, the autistic group showed differences in the activation strength of normative microstates during early-stage processing at all ages, suggesting consistent quantitative differences in the operation of typical processing pathways; qualitative differences in microstate topographies during late-stage processing became prominent in adults, suggesting the increasing involvement of non-typical neural systems with processing time and over development. CONCLUSIONS: These findings suggest that early difficulties with configural face processing may trigger later compensatory processes in autism that emerge in later development.

From the lab to the field: acceptability of using electroencephalography with Indian preschool children.

Background: Measurement of social and cognitive brain development using electroencephalography (EEG) offers the potential for early identification of children with elevated risk of developmental delay. However, there have been no published reports of how acceptable EEG technology is to parents and children within communities, especially in low-resource contexts such as in low and middle income countries (LMICs), which is an important question for the potential scalability of these assessments. We use a mixed-methods approach to examine whether EEG assessments are acceptable to children and their caregivers in a low resource community setting in India. Methods: We assessed the acceptability of neurophysiology research and Braintools (a novel neurodevelopmental assessment toolkit using concurrent EEG and eye-tracking technology) using: 1) a child engagement measure, 2) interviews with caregivers (n=8); 3) survey about caregiver's experience (n=36). Framework analysis was used to analyse interview data. Results: A high level of child engagement in EEG tasks was demonstrated, with children's gaze at the screen during the task averaging at 85.4% (±12.06%) of the task time. External distractions and noise during the tasks were measured, but not found to significantly effect child's attention to the screen during EEG tasks. Key topics were examined using the framework analysis: 1) parental experience of the assessment; and 2) the acceptability of research. From topic 1, four sub-themes were identified: i) caregivers' experience of the assessment, ii) caregivers' perception of child's experience of assessment, iii) logistical barriers and facilitators to participation, and iv) recommendations for improvement. Results from interviews and the survey indicated acceptability for gaze-controlled EEG research for parents and children. From topic 2, three themes were identified: i) caregivers' understanding of the research, ii) barriers to participation, and iii) facilitators to participation. Barriers to participation mainly included logistical challenges, such as geographic location and time, whereas involvement of the wider family in decision making was highlighted as an important facilitator to partake in the research. Conclusions: We demonstrate for the first time the acceptability of conducting neurodevelopmental assessments using concurrent EEG and eye-tracking in preschool children in uncontrolled community LMIC settings. This kind of research appears to be acceptable to the community and we identify potential barriers and facilitators of this research, thus allowing for future large scale research projects to be conducted investigating neurodevelopment and risk factors for suboptimal development in LMICs.

Reliability of an automated gaze-controlled paradigm for capturing neural responses during visual and face processing in toddlerhood.

Electroencephalography (EEG) has substantial potential value for examining individual differences during early development. Current challenges in developmental EEG research include high dropout rates and low trial numbers, which may in part be due to passive stimulus presentation. Comparability is challenged by idiosyncratic processing pipelines. We present a novel toolbox ("Braintools") that uses gaze-contingent stimulus presentation and an automated processing pipeline suitable for measuring visual processing through low-density EEG recordings in the field. We tested the feasibility of this toolbox in 61 2.5- to 4-year olds, and computed test-retest reliability (1- to 2-week interval) of event-related potentials (ERP) associated with visual (P1) and face processing (N290, P400). Feasibility was good, with 52 toddlers providing some EEG data at the first session. Reliability values for ERP features were moderate when derived from 20 trials; this would allow inclusion of 79% of the 61 toddlers for the P1 and 82% for the N290 and P400. P1 amplitude/latency were more reliable across sessions than for the N290 and P400. Amplitudes were generally more reliable than latencies. Automated and standardized solutions to collection and analysis of event-related EEG data would allow efficient application in large-scale global health studies, opening significant potential for examining individual differences in development.

EEG signatures of cognitive and social development of preschool children-a systematic review.

BACKGROUND: Early identification of preschool children who are at risk of faltering in their development is essential to ensuring that all children attain their full potential. Electroencephalography (EEG) has been used to measure neural correlates of cognitive and social development in children for decades. Effective portable and low-cost EEG devices increase the potential of its use to assess neurodevelopment in children at scale and particularly in low-resource settings. We conducted a systematic review aimed to synthesise EEG measures of cognitive and social development in 2-5-year old children. Our secondary aim was to identify how these measures differ across a) the course of development within this age range, b) gender and c) socioeconomic status (SES). METHODS AND FINDINGS: A systematic literature search identified 51 studies for inclusion in this review. Data relevant to the primary and secondary aims was extracted from these studies and an assessment for risk of bias was done, which highlighted the need for harmonisation of EEG data collection and analysis methods across research groups and more detailed reporting of participant characteristics. Studies reported on the domains of executive function (n = 22 papers), selective auditory attention (n = 9), learning and memory (n = 5), processing of faces (n = 7) and emotional stimuli (n = 8). For papers investigating executive function and selective auditory attention, the most commonly reported measures were alpha power and the amplitude and latency of positive (P1, P2, P3) and negative (N1, N2) deflections of event related potential (ERPs) components. The N170 and P1 ERP components were the most commonly reported neural responses to face and emotional faces stimuli. A mid-latency negative component and positive slow wave were used to index learning and memory, and late positive potential in response to emotional non-face stimuli. While almost half the studies described changes in EEG measures across age, only eight studies disaggregated results based on gender, and six included children from low income households to assess the impact of SES on neurodevelopment. No studies were conducted in low- and middle-income countries. CONCLUSION: This review has identified power across the EEG spectrum and ERP components to be the measures most commonly reported in studies in which preschool children engage in tasks indexing cognitive and social development. It has also highlighted the need for additional research into their changes across age and based on gender and SES.

Using multiple short epochs optimises the stability of infant EEG connectivity parameters.

Atypicalities in connectivity between brain regions have been implicated in a range of neurocognitive disorders. We require metrics to assess stable individual differences in connectivity in the developing brain, while facing the challenge of limited data quality and quantity. Here, we examine how varying core processing parameters can optimise the test-retest reliability of EEG connectivity measures in infants. EEG was recorded twice with a 1-week interval between sessions in 10-month-olds. EEG alpha connectivity was measured across different epoch lengths and numbers, with the phase lag index (PLI) and debiased weighted PLI (dbWPLI), for both whole-head connectivity and graph theory metrics. We calculated intra-class correlations between sessions for infants with sufficient data for both sessions (N's = 19-41, depending on the segmentation method). Reliability for the whole brain dbWPLI was higher across many short epochs, whereas reliability for the whole brain PLI was higher across fewer long epochs. However, the PLI is confounded by the number of available segments. Reliability was higher for whole brain connectivity than graph theory metrics. Thus, segmenting available data into a high number of short epochs and calculating the dbWPLI is most appropriate for characterising connectivity in populations with limited availability of EEG data.

Test-retest reliability of EEG network characteristics in infants.

INTRODUCTION: Functional Electroencephalography (EEG) networks in infants have been proposed as useful biomarkers for developmental brain disorders. However, the reliability of these networks and their characteristics has not been established. We evaluated the reliability of these networks and their characteristics in 10-month-old infants. METHODS: Data were obtained during two EEG sessions 1 week apart and was subsequently analyzed at delta (0.5-3 Hz), theta (3-6 Hz), alpha1 (6-9 Hz), alpha2 (9-12 Hz), beta (12-25 Hz), and low gamma (25-45 Hz) frequency bands. Connectivity matrices were created by calculating the phase lag index between all channel pairs at given frequency bands. To determine the reliability of these connectivity matrices, intra-class correlations were calculated of global connectivity, local connectivity, and several graph characteristics. RESULTS: Comparing both sessions, global connectivity, as well as global graph characteristics (characteristic path length and average clustering coefficient) are highly reliable across multiple frequency bands; the alpha1 and theta band having the highest reliability in general. In contrast, local connectivity characteristics were less reliable across all frequency bands. CONCLUSIONS: We conclude that global connectivity measures are highly reliable over sessions. Local connectivity measures show lower reliability over sessions. This research therefore underlines the possibility of these global network characteristics to be used both as biomarkers of neurodevelopmental disorders, but also as important factors explaining development of typical behavior.

Functional EEG connectivity in infants associates with later restricted and repetitive behaviours in autism; a replication study.

We conducted a replication study of our prior report that increased alpha EEG connectivity at 14-months associates with later autism spectrum disorder (ASD) diagnosis, and dimensional variation in restricted interests/repetitive behaviours. 143 infants at high and low familial risk for ASD watched dynamic videos of spinning toys and women singing nursery rhymes while high-density EEG was recorded. Alpha functional connectivity (7-8 Hz) was calculated using the debiased weighted phase lag index. The final sample with clean data included low-risk infants (N = 20), and high-risk infants who at 36 months showed either typical development (N = 47), atypical development (N = 21), or met criteria for ASD (N = 13). While we did not replicate the finding that global EEG connectivity associated with ASD diagnosis, we did replicate the association between higher functional connectivity at 14 months and greater severity of restricted and repetitive behaviours at 36 months in infants who met criteria for ASD. We further showed that this association is strongest for the circumscribed interests subdomain. We propose that structural and/or functional abnormalities in frontal-striatal circuits underlie the observed association. This is the first replicated infant neural predictor of dimensional variation in later ASD symptoms.

Task intentions and their implementation into actions: cognitive control from adolescence to middle adulthood.

Cognitive control processes involved in human multitasking arise, mature, and decline across age. This study investigated how age modulates cognitive control at two different levels: the level of task intentions and the level of the implementation of intentions into the corresponding actions. We were particularly interested in specifying maturation of voluntary task choice (intentions) and task-switching execution (their implementations) between adolescence and middle adulthood. Seventy-four participants were assigned to one of the four age groups (adolescents, 12-17 years; emerging adults, 18-22 years; young adults, 23-27 years; middle-aged adults, 28-56 years). Participants chose between two simple cognitive tasks at the beginning of each trial before pressing a spacebar to indicate that the task choice was made. Next, a stimulus was presented in one of the three adjacent boxes, with participants identifying either the location or the shape of the stimulus, depending on their task choice. This voluntary task-switching paradigm allowed us to investigate the intentional component (task choice) separately from its implementation (task execution). Although all participants showed a tendency to repeat tasks more often than switching between them, this repetition bias was significantly stronger in adolescents than in any adult group. Furthermore, participants generally responded slower after task switches than after task repetitions. This switch cost was similar across tasks in the two younger groups but larger for the shape than the location task in the two older groups. Together, our results demonstrate that both task intentions and their implementation into actions differ across age in quite specific ways.