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Neonatal neural responses to novelty related to behavioral inhibition at 1 year

Schwarzlose, Rebecca F; Filippi, Courtney A; Myers, Michael J; Harper, Jennifer; Camacho, M Catalina; Smyser, Tara A; Rogers, Cynthia E; Shimony, Joshua S; Warner, Barbara B; Luby, Joan L; Barch, Deanna M; Pine, Daniel S; Smyser, Christopher D; Fox, Nathan A; Sylvester, Chad M
Behavioral inhibition (BI), an early-life temperament characterized by vigilant responses to novelty, is a risk factor for anxiety disorders. In this study, we investigated whether differences in neonatal brain responses to infrequent auditory stimuli relate to children's BI at 1 year of age. Using functional magnetic resonance imaging (fMRI), we collected blood-oxygen-level-dependent (BOLD) data from N = 45 full-term, sleeping neonates during an adapted auditory oddball paradigm and measured BI from n = 27 of these children 1 year later using an observational assessment. Whole-brain analyses corrected for multiple comparisons identified 46 neonatal brain regions producing novelty-evoked BOLD responses associated with children's BI scores at 1 year of age. More than half of these regions (n = 24, 52%) were in prefrontal cortex, falling primarily within regions of the default mode or frontoparietal networks or in ventromedial/orbitofrontal regions without network assignments. Hierarchical clustering of the regions based on their patterns of association with BI resulted in two groups with distinct anatomical, network, and response-timing profiles. The first group, located primarily in subcortical and temporal regions, tended to produce larger early oddball responses among infants with lower subsequent BI. The second group, located primarily in prefrontal cortex, produced larger early oddball responses among infants with higher subsequent BI. These results provide preliminary insights into brain regions engaged by novelty in infants that may relate to later BI. The findings may inform understanding of anxiety disorders and guide future research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
PMID: 37971828
ISSN: 1939-0599
CID: 5610852

Children's social wariness toward a different-race stranger relates to individual differences in temperament

Hwang, Hyesung G; Filippi, Courtney A; Morales, Santiago; Fox, Nathan A; Woodward, Amanda
When children first meet a stranger, there is great variation in how much they will approach and engage with the stranger. While individual differences in this type of behavior-called social wariness-are well-documented in temperament research, surprisingly little attention has been paid to the social groups (such as race) of the stranger and how these characteristics might influence children's social wariness. In contrast, research on children's social bias and interracial friendships rarely examines individual differences in temperament and how temperament might influence cross-group interactions. The current study bridges the gap across these different fields of research by examining whether the racial group of an unfamiliar peer or adult moderates the association between temperament and the social wariness that children display. Utilizing a longitudinal dataset that collected multiple measurements of children's temperament and behaviors (including parent-reported shyness and social wariness toward unfamiliar adults and peers) across early childhood, we found that 2- to 7-year-old children with high parent-reported shyness showed greater social wariness toward a different-race stranger compared to a same-race stranger, whereas children with low parent-reported shyness did not. These results point to the importance of considering racial group membership in temperament research and the potential role that temperament might play in children's cross-race interactions. RESEARCH HIGHLIGHTS: Previous research on temperament has not considered how the race of strangers could influence children's social wariness. We find evidence that 2- to 7-year-old children with high parent-reported shyness show greater social wariness toward a different-race stranger compared to a same-race stranger. These results point to the importance of considering racial group membership in temperament research. Our findings also suggest temperament may play a role in children's cross-race interactions.
PMCID:10518028
PMID: 36960937
ISSN: 1467-7687
CID: 5605442

Cross-sectional and Longitudinal Associations of Anxiety and Irritability With Adolescents' Neural Responses to Cognitive Conflict

Cardinale, Elise M; Bezek, Jessica; Morales, Santiago; Filippi, Courtney; Smith, Ashley R; Haller, Simone; Valadez, Emilio A; Harrewijn, Anita; Phillips, Dominique; Chronis-Tuscano, Andrea; Brotman, Melissa A; Fox, Nathan A; Pine, Daniel S; Leibenluft, Ellen; Kircanski, Katharina
BACKGROUND:Psychiatric symptoms are commonly comorbid in childhood. The ability to disentangle unique and shared correlates of comorbid symptoms facilitates personalized medicine. Cognitive control is implicated broadly in psychopathology, including in pediatric disorders characterized by anxiety and irritability. To disentangle cognitive control correlates of anxiety versus irritability, the current study leveraged both cross-sectional and longitudinal data from early childhood into adolescence. METHODS:For this study, 89 participants were recruited from a large longitudinal research study on early-life temperament to investigate associations of developmental trajectories of anxiety and irritability symptoms (from ages 2 to 15) as well as associations of anxiety and irritability symptoms measured cross-sectionally at age 15 with neural substrates of conflict and error processing assessed at age 15 using the flanker task. RESULTS:Results of whole-brain multivariate linear models revealed that anxiety at age 15 was uniquely associated with decreased neural response to conflict across multiple regions implicated in attentional control and conflict adaptation. Conversely, irritability at age 15 was uniquely associated with increased neural response to conflict in regions implicated in response inhibition. Developmental trajectories of anxiety and irritability interacted in relation to neural responses to both error and conflict. CONCLUSIONS:Our findings suggest that neural correlates of conflict processing may relate uniquely to anxiety and irritability. Continued cross-symptom research on the neural correlates of cognitive control could stimulate advances in individualized treatment for anxiety and irritability during child and adolescent development.
PMID: 35358745
ISSN: 2451-9030
CID: 5364812

Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis

Bas-Hoogendam, Janna Marie; Bernstein, Rachel; Benson, Brenda E; Buss, Kristin A; Gunther, Kelley E; Pérez-Edgar, Koraly; Salum, Giovanni A; Jackowski, Andrea P; Bressan, Rodrigo A; Zugman, André; Degnan, Kathryn A; Filippi, Courtney A; Fox, Nathan A; Henderson, Heather A; Tang, Alva; Zeytinoglu, Selin; Harrewijn, Anita; Hillegers, Manon H J; White, Tonya; van IJzendoorn, Marinus H; Schwartz, Carl E; Felicione, Julia M; DeYoung, Kathryn A; Shackman, Alexander J; Smith, Jason F; Tillman, Rachael M; van den Berg, Yvonne H M; Cillessen, Antonius H N; Roelofs, Karin; Tyborowska, Anna; Hill, Shirley Y; Battaglia, Marco; Tettamanti, Marco; Dougherty, Lea R; Jin, Jingwen; Klein, Daniel N; Leung, Hoi-Chung; Avery, Suzanne N; Blackford, Jennifer Urbano; Clauss, Jacqueline A; Hayden, Elizabeth P; Liu, Pan; Vandermeer, Matthew R J; Goldsmith, H Hill; Planalp, Elizabeth M; Nichols, Thomas E; Thompson, Paul M; Westenberg, P Michiel; van der Wee, Nic J A; Groenewold, Nynke A; Stein, Dan J; Winkler, Anderson M; Pine, Daniel S
Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT).2 IT is a moderately heritable trait1 that can be measured in multiple species.3 In humans, levels of IT can be quantified from the first year of life through direct behavioral observations or reports by caregivers or teachers. Similar approaches as well as self-report questionnaires on current and/or retrospective levels of IT1 can be used later in life.
PMCID:9434711
PMID: 36038199
ISSN: 1527-5418
CID: 5364822

Developmental pathways to social anxiety and irritability: The role of the ERN - CORRIGENDUM

Filippi, Courtney A; Subar, Anni R; Sachs, Jessica F; Kircanski, Katharina; Buzzell, George; Pagliaccio, David; Abend, Rany; Fox, Nathan A; Leibenluft, Ellen; Pine, Daniel S
PMID: 34581264
ISSN: 1469-2198
CID: 5364772

Developmental Changes in the Association Between Cognitive Control and Anxiety

Filippi, Courtney A; Subar, Anni; Ravi, Sanjana; Haas, Sara; Troller-Renfree, Sonya V; Fox, Nathan A; Leibenluft, Ellen; Pine, Daniel S
Anxiety has been associated with reliance on reactive (stimulus-driven/reflexive) control strategies in response to conflict. However, this conclusion rests primarily on indirect evidence. Few studies utilize tasks that dissociate the use of reactive ('just in time') vs. proactive (anticipatory/preparatory) cognitive control strategies in response to conflict, and none examine children diagnosed with anxiety. The current study utilizes the AX-CPT, which dissociates these two types of cognitive control, to examine cognitive control in youth (ages 8-18) with and without an anxiety diagnosis (n = 56). Results illustrate that planful behavior, consistent with using a proactive strategy, varies by both age and anxiety symptoms. Young children (ages 8-12 years) with high anxiety exhibit significantly less planful behavior than similarly-aged children with low anxiety. These findings highlight the importance of considering how maturation influences relations between anxiety and performance on cognitive-control tasks and have implications for understanding the pathophysiology of anxiety in children.
PMCID:9107422
PMID: 33738691
ISSN: 1573-3327
CID: 5364762

Temperamental risk for anxiety: emerging work on the infant brain and later neurocognitive development

Filippi, Courtney A; Valadez, Emilio A; Fox, Nathan A; Pine, Daniel S
Behavioral inhibition (BI), an infant temperament characterized by distress to novelty, is amongst the strongest early risk markers for future anxiety. In this review, we highlight three ways that recent research elucidates key details about the pathophysiology of anxiety in individuals with BI. First, atypical amygdala connectivity during infancy may be related to BI. Second, developmental shifts in cognitive control may portend risk for anxiety for children with BI. Lastly, distinct cognitive control processes moderate the BI-anxiety relation in different ways. Studying the intersection of these three streams of work may inform prevention or intervention work.
PMCID:8955382
PMID: 35342779
ISSN: 2352-1546
CID: 5364802

An ode to fetal, infant, and toddler neuroimaging: Chronicling early clinical to research applications with MRI, and an introduction to an academic society connecting the field

Pollatou, Angeliki; Filippi, Courtney A; Aydin, Ezra; Vaughn, Kelly; Thompson, Deanne; Korom, Marta; Dufford, Alexander J; Howell, Brittany; Zöllei, Lilla; Martino, Adriana Di; Graham, Alice; Scheinost, Dustin; Spann, Marisa N
Fetal, infant, and toddler neuroimaging is commonly thought of as a development of modern times (last two decades). Yet, this field mobilized shortly after the discovery and implementation of MRI technology. Here, we provide a review of the parallel advancements in the fields of fetal, infant, and toddler neuroimaging, noting the shifts from clinical to research use, and the ongoing challenges in this fast-growing field. We chronicle the pioneering science of fetal, infant, and toddler neuroimaging, highlighting the early studies that set the stage for modern advances in imaging during this developmental period, and the large-scale multi-site efforts which ultimately led to the explosion of interest in the field today. Lastly, we consider the growing pains of the community and the need for an academic society that bridges expertise in developmental neuroscience, clinical science, as well as computational and biomedical engineering, to ensure special consideration of the vulnerable mother-offspring dyad (especially during pregnancy), data quality, and image processing tools that are created, rather than adapted, for the young brain.
PMCID:8861425
PMID: 35184026
ISSN: 1878-9307
CID: 5443282

Dear reviewers: Responses to common reviewer critiques about infant neuroimaging studies

Korom, Marta; Camacho, M Catalina; Filippi, Courtney A; Licandro, Roxane; Moore, Lucille A; Dufford, Alexander; Zöllei, Lilla; Graham, Alice M; Spann, Marisa; Howell, Brittany; Shultz, Sarah; Scheinost, Dustin
The field of adult neuroimaging relies on well-established principles in research design, imaging sequences, processing pipelines, as well as safety and data collection protocols. The field of infant magnetic resonance imaging, by comparison, is a young field with tremendous scientific potential but continuously evolving standards. The present article aims to initiate a constructive dialog between researchers who grapple with the challenges and inherent limitations of a nascent field and reviewers who evaluate their work. We address 20 questions that researchers commonly receive from research ethics boards, grant, and manuscript reviewers related to infant neuroimaging data collection, safety protocols, study planning, imaging sequences, decisions related to software and hardware, and data processing and sharing, while acknowledging both the accomplishments of the field and areas of much needed future advancements. This article reflects the cumulative knowledge of experts in the FIT'NG community and can act as a resource for both researchers and reviewers alike seeking a deeper understanding of the standards and tradeoffs involved in infant neuroimaging.
PMCID:8733260
PMID: 34974250
ISSN: 1878-9307
CID: 5364782

Parenting and childhood irritability: Negative emotion socialization and parental control moderate the development of irritability

Ravi, Sanjana; Havewala, Mazneen; Kircanski, Katharina; Brotman, Melissa A; Schneider, Leslie; Degnan, Kathryn; Almas, Alisa; Fox, Nathan; Pine, Daniel S; Leibenluft, Ellen; Filippi, Courtney
Irritability, characterized by anger in response to frustration, is normative in childhood. While children typically show a decline in irritability from toddlerhood to school age, elevated irritability throughout childhood may predict later psychopathology. The current study (n = 78) examined associations between trajectories of irritability in early childhood (ages 2-7) and irritability in adolescence (age 12) and tested whether these associations are moderated by parenting behaviors. Results indicate that negative emotion socialization moderated trajectories of irritability - relative to children with low stable irritability, children who exhibited high stable irritability in early childhood and who had parents that exhibited greater negative emotion socialization behaviors had higher irritability in adolescence. Further, negative parental control behavior moderated trajectories of irritability - relative to children with low stable irritability, children who had high decreasing irritability in early childhood and who had parents who exhibited greater negative control behaviors had higher irritability in adolescence. In contrast, positive emotion socialization and control behaviors did not moderate the relations between early childhood irritability and later irritability in adolescence. These results suggest that both irritability in early childhood and negative parenting behaviors may jointly influence irritability in adolescence. The current study underscores the significance of negative parenting behaviors and could inform treatment.
PMCID:9289071
PMID: 35039102
ISSN: 1469-2198
CID: 5364792