Nathan A. Fox’s research while affiliated with Loyola University Maryland and other places

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Publications (758)


Longitudinal changes in infant attention-related brain networks and fearful temperament
  • Preprint

January 2025

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11 Reads

Courtney A. Filippi

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Alice Massera

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Jiayin Xing

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[...]

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Anxiety disorders are hypothesized to stem in part from altered development of attention-related brain networks. These networks, including the dorsal attention network (DAN), frontal parietal network (FPN), salience network (SN), and default mode network (DMN), are crucial for regulating attention to salient environmental cues. Altered resting-state functional connectivity (rsFC) among these networks in the first months of life relates to fearful temperament, a risk marker for anxiety. Nevertheless, it remains unclear how these networks develop beyond these initial months, particularly in fearful infants. This study characterizes the development of attention-related brain networks over the first two years of life and identifies rsFC changes associated with fearful temperament. Using data from the Baby Connectome Project (from 180 infants across 396 sessions), we analyzed rsFC among the DMN, SN, DAN, and FPN. We examined age-related changes in rsFC across these networks and their relations with fearful temperament at age 2. Results demonstrated age-related decreases in rsFC in DAN-FPN and DMN-SN. Less decrease in DAN-FPN rsFC over time related to greater fear at age 2. This pattern manifested in analyses relating longitudinal trajectories of rsFC and fearful temperament across all available timepoints. Low initial DAN-SN rsFC related to increasing fearfulness over time. This study provides novel insights into the neurodevelopmental origins of fearful temperament.


Consolidated Standards of Reporting Trials (CONSORT) diagram for the current study
Estimated growth curves for physical and neurophysiological measures. Curves were fit with a quadratic polynomial, except for head circumference, which was fit with a cubic polynomial. Confidence intervals not pictured to improve readability. CAUG +ADHD, care as usual group with ADHD; CAUG −ADHD, care as usual group without ADHD; FCG +ADHD, foster care group with ADHD; FCG −ADHD, foster care group without ADHD; NIG, never institutionalized group
Physical and neurophysiological maturation associated with ADHD among previously institutionalized children: a randomized controlled trial
  • Article
  • Publisher preview available

January 2025

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23 Reads

Background Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental outcome among children with a history of early institutional care. Prior research on institutionalized children suggested that accelerated physical growth in childhood is a risk factor for ADHD outcomes. Methods The current study examined physical and neurophysiological growth trajectories among institutionalized children randomized to foster care treatment (n = 59) or care as usual (n = 54), and never institutionalized children (n = 64) enrolled in the Bucharest Early Intervention Project (NCT00747396, clinicaltrials.gov). Participants completed physical and electroencephalography (EEG) assessments at six time points from infancy through adolescence, as well as structured diagnostic interviews at the 54‐month and 12‐year time points. A series of multilevel growth models and cross‐lagged path models were estimated to examine associations among physical and neurophysiological maturation, treatment group, age of foster care placement, and ADHD diagnostic outcomes. Results Twenty‐seven percent of the institutionalized children met research criteria for ADHD at one or both time points. Slowed, prolonged growth of height and head circumference were associated with both ADHD and delayed foster care placement. Placement in foster care versus care as usual, but not ADHD, was associated with maturation of the peak alpha frequency. Among children randomized to foster care, average theta‐beta ratio was lower among those with ADHD. There was no evidence that rapid physical maturation led to atypical cortical activity. Conclusions Delayed, prolonged physical growth and atypical neurophysiology from infancy through adolescence is associated with ADHD among institutionalized children, over and above the protective effects of foster care.

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Figure 1 Event-Related Potentials Waveforms and Topography
Figure 2 CDR Waveforms for Each Condition and ROI
Figure 3 Mean CDR Values for Source-Localized ERPs Around the Peak for Each ROI
Demographics for the Subset of Infants With Complete and Usable EEG and MRI Data
Infants’ Resting-State Functional Connectivity and Event-Related Potentials: A Multimodal Approach to Investigating the Neural Basis of Infant Novelty Detection

January 2025

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28 Reads

Developmental Psychology

Individual differences in how the brain responds to novelty are present from infancy. A common method of studying novelty processing is through event-related potentials (ERPs). While ERPs possess millisecond precision, spatial resolution remains poor, especially in infancy. This study aimed to balance spatial and temporal precision by combining ERP data with functional magnetic resonance imaging (fMRI) data. Twenty-nine infants (15 female) underwent resting-state fMRI (Mage = 4.73 months) and electroencephalography (EEG) during a three-stimulus auditory oddball task (Mage = 5.19 months). The mismatch response (MMR) and P3 were computed from ERP data, and resting-state functional connectivity (rs-FC) was computed from fMRI data. We first source localized the MMR and P3 responses to five regions-of-interest (ROIs), based on prior literature. We then performed network-level enrichment analyses to identify associations between rs-FC and MMR and P3, at each of the five ROIs. In line with prior work, source-localized EEG analyses implicated the bilateral auditory cortices, posterior cingulate cortex, and superior parietal cortex in the generation of MMR and P3 responses. The MMR and P3 related to functional connectivity within the somatomotor network as well as between the somatomotor and the dorsal and ventral attention networks (DAN/VAN). This was especially true for novelty response ERPs recorded at superior parietal lobule, known for its implications in initial reorienting to novel stimuli. The DAN, known for its implication in initial reorienting to support novelty detection, was implicated for the MMR. In contrast, the VAN, known for its support of later-stage, complex adjustments in attention, related to the later P3. This work further solidifies our understanding of the underlying networks implicated in the development of immediate responses to stimuli. Altered configurations of such networks may increase the risk for heightened sensitivity to novelty in certain individuals, which could have behavioral and clinical significance.


The Effect of a Monthly Unconditional Cash Transfer on Children’s Development at Four Years of Age: A Randomized Controlled Trial in the U.S.

December 2024

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25 Reads

Developmental differences between children growing up in poverty and their higher-income peers are frequently reported. However, the extent to which such differences are caused by differences in family income is unclear. To study the causal role of income on children’s development, the Baby’s First Years randomized control trial provided families with monthly unconditional cash transfers. One thousand racially and ethnically diverse mothers with incomes below the U.S. federal poverty line were recruited from postpartum wards in 2018-19, and randomized to receive either 333/monthor333/month or 20/month for the first several years of their children’s lives. After the first four years of the intervention (n=891), we find no statistically significant impacts of the cash transfers on four preregistered primary outcomes (language, executive function, social-emotional problems, and high-frequency brain activity) nor on three secondary outcomes (visual processing/spatial perception, pre-literacy, maternal reports of developmental diagnoses). Possible explanations for these results are discussed.


The impact of a monthly unconditional cash transfer on child brain activity: A 4-year follow-up

December 2024

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54 Reads

Early childhood poverty is associated with neurodevelopmental differences, but causal evidence linking income to brain development is sparse. In the present study, we examine whether four years of monthly unconditional cash transfers to mothers experiencing low income cause differences in their preschoolers’ brain activity. Shortly after giving birth, mothers were randomized to receive 333/monthor333/month or 20/month. We find no impact on our primary preregistered outcome (an aggregated index of mid-to-high-frequency brain activity) or our secondary preregistered outcome frontal gamma power. In additional analyses that were part of our pre-registered analytic plan, we find that preschoolers in the high-cash gift group have higher alpha power than those in the low-cash gift group, but no differences in theta, beta, or gamma power. These findings suggest monthly unconditional cash transfers may have impacts on children’s alpha power during the preschool years, although this evidence needs further investigation and replication.


From Deconstruction to Reconstruction: A Search for Natural Kinds in Developmental Psychopathology

November 2024

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9 Reads

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1 Citation

Journal of Psychopathology and Clinical Science

A “natural kind” is a specific classification that identifies some structure of truth and reality, a delimited entity. Psychiatric disorders are not natural kinds. As one moves from physics and chemistry to biology and medicine, natural kinds degrade, and the boundaries of differentiating phenomena become less clear. Within psychiatry, the categorization of psychopathology has further ontological challenges, especially across development. We suggest that to identify and isolate clinical subgroups, it is critical to integrate external validators in an iterative process, with the goal of linking classification to treatments with maximal clinical benefit.



Exploring Background Aperiodic Electroencephalography (EEG) Activity in the Bucharest Early Intervention Project

September 2024

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36 Reads

Developmental Psychology

Aperiodic activity is a background arrhythmic component of electroencephalogram (EEG) that is present in the power spectrum and characterized by an aperiodic offset and an aperiodic exponent. These components have been proposed as a marker of brain maturation, reflecting alterations in excitatory–inhibitory (E:I) balance and exhibiting developmental changes over time. Currently, there is limited understanding regarding how aperiodic activity changes over the course of an individual’s life, particularly from early childhood to adolescence, a period when the brain undergoes significant structural and functional transformation. More importantly, considering that brain development is affected by early experience, there is no evidence on how early adversity might affect these parameters. Here, we examined the developmental trajectories of aperiodic activity from EEG data collected in the Bucharest Early Intervention Project, from early childhood to mid adolescence (from 42 months of age up to 16 years old). We examined the effects of a history of early adversity and the impact of early intervention on background aperiodic EEG activity. Surprisingly, we found little influence of a history of adversity or early intervention on these characteristics of the signal. Rather, we found nonlinear age-related trajectories in both aperiodic offset and aperiodic exponent and sex differences in the trajectory for aperiodic offset (but not exponent). These findings provide information on the maturational patterns and trajectories of brain development from early childhood to mid adolescence and how background aperiodic activity describes one aspect of EEG development.


Fig. 8. Conceptual schematic of the data flow used by HBCD to move EEG data from the collection site to the central storage and processing servers.
Number of infants who contributed data to the piloting process. This information was used to determine task parameters for the full HBCD Study.
The development and structure of the HEALthy Brain and Child Development (HBCD) Study EEG protocol

September 2024

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100 Reads

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6 Citations

Developmental Cognitive Neuroscience

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Electroencephalography (EEG) is one of two brain imaging modalities central to the HBCD Study. EEG records electrical signals from the scalp that reflect electrical brain activity. In addition, the EEG signal can be synchronized to the presentation of discrete stimuli (auditory or visual) to measure specific cognitive processes with excellent temporal precision (e.g., event-related potentials; ERPs). EEG is particularly helpful for the HBCD Study as it can be used with awake, alert infants, and can be acquired continuously across development. The current paper reviews the HBCD Study’s EEG/ERP protocol: (a) the selection and development of the tasks (Video Resting State, Visual Evoked Potential, Auditory Oddball, Face Processing); (b) the implementation of common cross-site acquisition parameters and hardware, site setup, training, and initial piloting; (c) the development of the preprocessing pipelines and creation of derivatives; and (d) the incorporation of equity and inclusion considerations. The paper also provides an overview of the functioning of the EEG Workgroup and the input from members across all steps of protocol development and piloting.


Cohort Characteristics.
Altered associations between white matter structure and psychopathology in previously institutionalized adolescents

September 2024

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32 Reads

Developmental Cognitive Neuroscience

Previously institutionalized adolescents show increased risk for psychopathology, though placement into high-quality foster care can partially mitigate this risk. White matter (WM) structure is associated with early institutional rearing and psychopathology in youth. Here we investigate associations between WM structure and psychopathology in previously institutionalized youth. Adolescent psychopathology data were collected using the MacArthur Health and Behavior Questionnaire. Participants underwent diffusion MRI, and data were processed using fixel-based analyses. General linear models investigated interactions between institutionalization groups and psychopathology on fixel metrics. Supplementary analyses also examined the main effects of psychopathology and institutionalization group on fixel metrics. Ever–Institutionalized children included 41 randomized to foster care (Mage=16.6), and 40 to care-as-usual (Mage=16.7)). In addition, 33 participants without a history of institutionalization were included as a reference group (Mage=16.9). Ever–Institutionalized adolescents displayed altered general psychopathology–fixel associations within the cerebellar peduncles, inferior longitudinal fasciculi, corticospinal tract, and corpus callosum, and altered externalizing–fixel associations within the cingulum and fornix. Our findings indicate brain–behavior associations reported in the literature may not be generalizable to all populations. Previously institutionalized youth may develop differential brain development, which in turn leads to altered neural correlates of psychopathology that are still apparent in adolescence.


Citations (57)


... Baseline EEG was recorded at each visit using largely harmonized a priori protocols across visit ages and between sites. Infants were seated on their caregiver's lap approximately 60 cm in front of a computer monitor (30 x 45.5 cm, 1440 x 900-pixel resolution) throughout recording where they passively viewed a video of moving shapes as in (Fox et al., 2024). The video was programmed and presented in E-Prime (Psychology Software Tools, Inc., Sharpsburg, PA). ...

Reference:

Spatiotemporal dynamics of EEG microstate networks over the first two years of life: A multi-cohort longitudinal study
The development and structure of the HEALthy Brain and Child Development (HBCD) Study EEG protocol

Developmental Cognitive Neuroscience

... Finally, the present study explored whether impacts of the highcash gift on measures of child development were moderated by the following participant characteristics: child sex assigned at birth, maternal educational attainment, and depth of family poverty at study entry. Each of these characteristics could shape the extent to which the cash gifts affected the mechanisms hypothesized to impact child development (increased investments and reduced stress; see Gennetian et al., 2024;. Income-boosting programs often result in heterogeneous impacts by child sex, with some evidence that boys benefit more than girls from increases in income (see Huston et al., 2005) and other work suggesting the opposite (see Tanner et al., 2015). ...

Effects of a monthly unconditional cash transfer starting at birth on family investments among US families with low income

Nature Human Behaviour

... Different frequency components can be related in certain ways to certain cognitive processes and mental events. For example, the characteristics of oscillations in the θ band (between 4 and 8 Hz) are associated with memory, learning [26], voluntary attention and mental selectivity [27], and high cognitive performance [28,5,7]. Therefore, it is possible that the EEG θ band, as a correlate of integrative information processing, can be correlated to NC. ...

Theta activity and cognitive functioning: Integrating evidence from resting-state and task-related developmental electroencephalography (EEG) research

Developmental Cognitive Neuroscience

... Although a vast literature in the United States finds some, mostly small, labour market responses to income support 51,52 , as shown in Fig. 2 (see also Supplementary Table 3 for more details), mothers in the high-cash gift group were no more or less likely to spend time in paid work; however, mothers in the high-cash gift group were more likely to report working 20 h or less a week (95% CI 0.000 to 0.047, P = 0.049) as well as less likely to report working 40 h or more a week (95% CI −0.082 to −0.006, P = 0.025). There were no statistically significant differences in timing of mothers' labour market entry or re-entry overall, or their full-time employment in the first year after the child's birth 53 . There is no evidence that mothers' participation in a joint measure of education and training differed by cash gift treatment group in pooled estimates (Supplementary Table 3). ...

Unconditional Cash and Breastfeeding, Child Care, and Maternal Employment among Families with Young Children Residing in Poverty
  • Citing Article
  • May 2024

Social Service Review

... As children become older, it is also common to assess resting EEG under eyes-open and eyes-closed conditions. Following these recordings, brain activity is often quantified in terms of the magnitude of brain oscillations (power) in different frequency bands (denoted by Greek letters: delta, theta, alpha, beta, and gamma)-which are thought to be functionally significant for neurocognition (Begus & Bonawitz, 2020;Bell & Cuevas, 2012;Saby & Marshall, 2012;Tan, Troller-Renfree, et al., 2023;Troller-Renfree et al., 2023). Resting EEG measures in children are commonly cited as valuable early markers of learning and cognition (e.g., language, executive function, IQ); with many studies showing prospective associations with neurocognition (Benasich et al., 2008;Brito et al., 2016;Gou et al., 2011;Tan, Tang, et al., 2023;Wilkinson et al., 2019) and mental health (Brito et al., 2019;McLaughlin et al., 2010;Troller-Renfree et al., 2017). ...

Theta activity and cognitive functioning: Integrating evidence from resting-state and task-related developmental electroencephalography (EEG) research
  • Citing Preprint
  • October 2023

... Research links rsFC among these networks to fearful infant temperament (4,7). Specifically, greater rsFC within the SN (7,9,41), less rsFC within the DMN (4,10), and less rsFC between the DAN -DMN, -SN, and -FPN (8) has been related to fearfulness in infancy. ...

Neural Correlates of Novelty-Evoked Distress in 4-Month-Old Infants: A Synthetic Cohort Study
  • Citing Article
  • April 2024

... In contrast to the ERPs, measures from the Resting State task all displayed excellent reliability even with minimal data. This replicates previous studies examining the internal consistency reliability of Resting State measures (Hernandez et al., 2024;Leach et al., 2020;Lopez et al., 2023;Troller-Renfree et al., 2021) and highlights their utility as individual difference measures. Importantly, these age-related and ERP component-related differences in reliability indicate that the internal consistency of a dataset is intrinsic and context-dependent (Clayson, 2020;Morales et al., 2022). ...

Examining the impact of prenatal maternal internalizing symptoms and socioeconomic status on children's frontal alpha asymmetry and psychopathology
  • Citing Article
  • March 2024

Developmental Psychobiology

... Applying prior knowledge of existing therapies to patient populations with AD-SUD comorbidity will help inform development of novel integrated treatments and application of existing behavioral therapies to this population. For example, cognitive behavioral therapy (CBT) has been shown to normalize hyperactivity in fronto-parietal networks, including the PFC, in patients with ADs [188]. Integrated AD-SUD treatments may focus on CBT during the preoccupation/anticipation phase when high anxiety levels exacerbate dysfunction in the PFC and contribute to further drug consumption. ...

Normalization of Fronto-Parietal Activation by Cognitive-Behavioral Therapy in Unmedicated Pediatric Patients With Anxiety Disorders
  • Citing Article
  • January 2024

American Journal of Psychiatry

... Although this link was strongly affected by factors such as maternal psychopathology, the child's gender, and the child's substance use, the influence on the delta power band persisted even after adjusting for these covariates. Our findings are consistent with previous studies (Pini et al., 2024;Shuffrey et al., 2020), and particularly our recent study in children (Jansone et al., 2023), which identified significant effects in resting-state EEG power bands (delta and theta) as direct effects, independent of potential covariates such as child's sex, age, maternal age, smoking habits before pregnancy, alcohol consumption during pregnancy, gestation age, and psychopathology. ...

In Utero Exposure to Alcohol and Tobacco and Electroencephalogram Power During Childhood
  • Citing Article
  • January 2024

JAMA Network Open

... They observed a correlation between the amplitude of the brain activation during omissions and language development at 12 and 18 months. In neonates, Schwarzlose et al. (2023) using fMRI and an auditory oddball protocol reported that larger BOLD responses to deviants were related to behavioral inhibition, a precursor of anxiety, at 1 year of age. These findings are exciting as they open new venues of research to understand neurodevelopment and its behavioral and clinical manifestations. ...

Neonatal Neural Responses to Novelty Related to Behavioral Inhibition at 1 Year

Developmental Psychology