Joint attention and brain functional connectivity in infants and toddlers
Open accessAbstract
Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development.
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Written from the paper’s full text.
TL;DR
In a semilongitudinal cohort of infants and toddlers, initiating joint attention (IJA) increased markedly from 12 to 24 months and was related to resting-state functional connectivity, with the strongest brain–behavior associations clustered in a small subset of functional network pairs. The most consistent implicated pairs were visual–dorsal attention and visual–posterior cingulate default mode network connections.
Key findings
- IJA increased strongly with age: across the larger behavioral sample (n = 429 at 12 months, n = 384 at 24 months, 311 with both), Wilcoxon signed-rank test z = −11.8, P < 3.4 × 10−32.
- Among 116 12-month infants and 98 24-month toddlers with usable fcMRI and behavioral data, individual ROI-pair brain–behavior correlations were moderate and none passed Bonferroni correction; stronger correlations clustered within specific functional network pairs.
- At 12 months, significantly enriched network pairs were Vis-pcDMN (P < 1.3 × 10−2), Vis-DAN (P < 5.4 × 10−3), SMN2-aDMN (P < 7.5 × 10−3), and SMN2-SMN (P < 1.9 × 10−2); at 24 months, they were aFPC-DAN (P < 2.0 × 10−2), aFPC-aFPC (P < 3.6 × 10−2), and Sal-aDMN (P < 4.3 × 10−2).
- Only 2 of 91 network pairs were both significantly enriched at one age and significantly different across age: Vis-DAN and Vis-pcDMN; the global set of ROI-pair brain–behavior relationships differed between age groups (McNemar χ2 = 4.5, P < 1.7 × 10−2), with nearly 8% more strong ROI-pair correlations at 24 months.
Methods
- Participants were from the Infant Brain Imaging Study, including low- and high-familial-risk infants for ASD; IJA was assessed with the CSBS-DP at 12 and 24 months, and resting-state fcMRI was acquired during unsedated natural sleep on identical 3-T Siemens TIM Trio scanners.
- Analyses used 230 usable ROIs and 26,335 ROI pairs; pairwise Pearson correlations were Fisher-z transformed, and a cross-age functional network model was derived from 48 children with data at both time points using Infomap consensus clustering, yielding 13 putative networks.
- Brain–behavior relationships were tested with Spearman correlations between ROI-pair fcMRI and IJA scores, followed by enrichment analyses using χ2 and hypergeometric tests with 1,000,000 permutations; McNemar χ2 tests compared 12- and 24-month brain–behavior relationships.
Limitations
- The paper states that the ROIs derive from work in older subjects and may be extended to infant/toddler functional areal parcellations in the future.
- The paper states that fcMRI was acquired during natural sleep without EEG polysomnography, so sleep-stage differences within and between age groups may complicate interpretation.
- The paper states that the study was not designed or powered to test differences between high- and low-risk groups or ASD outcomes, and the sample was too small for within-age risk/diagnostic subgroup comparisons; evident from the text, the design is correlational and many network-pair findings were discovery results not statistically different across age.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 35 cited sources checked · 0 supported · 0 flagged
- Findingown data
The strongest brain-behavior associations include connections between the visual network and posterior cingulate aspects of the default mode network.
“In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network.”
Quote in the paperSubstantial claim - Findingown data
The functional organization of the brain is intimately related to the emergence of IJA.
“Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers.”
Quote in the paperSubstantial claim - Findingown data
Functional connections spanning the brain are involved in IJA.
“In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network.”
Quote in the paperSubstantial claim - Findingown data
The strongest brain-behavior associations cluster within connections between a small subset of functional brain networks.
“In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network.”
Quote in the paperSubstantial claim - Findingown data
There were nearly 8% more strong ROI-pair brain-behavior correlations at 24 months than at 12 months.
“partially driven by there being nearly 8% more strong ROI-pair brain-behavior correlations at 24 mo.”
Quote in the paperNot a substantial claim
- Findingown data
Only 3 of 91 functional network pairs exhibited a significantly different set of brain-behavior relationships between 12 and 24 months (Vis-DAN, Vis-pcDMN, tDMN-tDMN).
“Additionally, only 3 (of 91 total) functional network pairs exhibited a significantly different set of brain-behavior relationships between 12 mo and 24 mo (Fig. 2D, Vis-DAN, McNemar brain-wide FPR P < 6.5 × 10−3; Vis-pcDMN, P < 2.2 × 10−2; tDMN-tDMN, P < 5.0 × 10−2).”
Quote in the paperSubstantial claim - Findingown data
At 24 months, there was no relationship between the number of ROI pairs within a network pair and the brain-wide false-positive rejection rate.
“or at 24 mo (χ2, r = −0.05, P < 6.2 × 10−1; hypergeometric, r = −0.03, P < 7.8 × 10−1; Supplementary Fig. 2G).”
Quote in the paperNot a substantial claim - Findingown data
Functional network pairs containing a significant clustering of strong brain-behavior correlations at 12 months (Vis-pcDMN, Vis-DAN, SMN2-aDMN, SMN2-SMN) did not overlap with those observed at 24 months (aFPC-DAN, aFPC-aFPC, Sal-aDMN).
“Functional network pairs containing a significant clustering of strong brain-behavior correlations at 12 mo (Vis-pcDMN, hypergeometric brain-wide FPR P < 1.3 × 10−2; Vis-DAN, P < 5.4 × 10−3; SMN2-aDMN, P < 7.5 × 10−3; SMN2-SMN, P < 1.9 × 10−2) did not overlap with those observed at 24 mo (aFPC-DAN, P < 2.0 × 10−2; aFPC-aFPC, P < 3.6 × 10−2; Sal-aDMN, P < 4.3 × 10−2; Fig. 2C).”
Quote in the paperSubstantial claim - Findingown data
At 24 months, strong correlations between functional connectivity and IJA are more distributed throughout the brain.
“At 24 mo, though 8% more ROI pairs have strong correlations between fc and IJA, these strong correlations are more distributed throughout the brain”
Quote in the paperSubstantial claim - Findingreasoning
The adult-functional network pairs displayed a qualitatively more heterogeneous set of brain-behavior relationships than those obtained using the infant-toddler networks.
“The adult-functional network pairs displayed a qualitatively more heterogeneous set of brain-behavior relationships than those obtained using the infant–toddler networks”
Quote in the paperNot a substantial claim - Findingown data
Within the implicated networks, the sign of the fcMRI correlation values themselves was also generally conserved across ROI pairs.
“Additionally, within these networks, the sign of the fcMRI correlation values themselves was also generally conserved across ROI pairs (Fig. 4).”
Quote in the paperNot a substantial claim - Findingown data
The global set of brain-behavior relationships at the ROI-pair level was different between the 12-month and 24-month age groups.
“Overall, the global set of brain-behavior relationships at the ROI-pair level were different between the 2 age groups (McNemar χ2 = 4.5, P < 1.7 × 10−2)”
Quote in the paperSubstantial claim - Findingown data
Only 2 of 91 network pairs were both significantly associated with IJA at a given age and significantly different in their set of brain-behavior relationships across age: Vis-DAN and Vis-pcDMN.
“only 2 of 91 network pairs were both significantly associated with IJA at a given age and significantly different in their set of brain-behavior relationships across age: Vis-DAN and Vis-pcDMN (Fig. 2E, Supplementary Table 2).”
Quote in the paperSubstantial claim - Findingown data
Stronger brain-behavior correlations of matching sign generally clustered within functional network pairs.
“However, stronger brain-behavior correlations of matching sign generally clustered within functional network pairs (e.g., the grouping of dark blue correlation values in the Vis-DAN block at 12 mo; Fig. 2B).”
Quote in the paperSubstantial claim - Findingown data
In 4 of the 7 significantly enriched infant-toddler functional network pairs, general consistency was present in the signs of the brain-behavior correlations (all at 12 months), whether the correlations were significantly positive (Vis-pcDMN, SMN2-aDMN) or negative (Vis-DAN, SMN2-SMN).
“In 4 of the 7 significantly enriched infant–toddler functional network pairs, general consistency was present in the signs of the brain-behavior correlations (all at 12 mo, Figs 3 and 4), whether or not the correlations were significantly positive (Vis-pcDMN [t-test of sign vs. zero, t = 9.2, P < 3.5 × 10−11], SMN2-aDMN [t = 9.2, P < 1.4 × 10−11]) or negative (Vis-DAN [t = −19.9, P < 6.8 × 10−32]”
Quote in the paperSubstantial claim - Findingown data
The patterns of brain-behavior relationships were also detectable when using a brain functional network structure derived from a previously published independent fcMRI data set of typical adults.
“These patterns were also detectable when using a brain functional network structure derived from a previously published independent fcMRI data set of typical adults (Power et al. 2011) (Supplementary Figs 1C and 3).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Power et al. 2011 source
Not checked in the free run.
- Study design and conductown data
Age-in-months was not correlated with IJA score within time point at 24 months.
“There was no effect of site on IJA scores (F = 0.97, P = 0.41), and age-in-months was not correlated with IJA score within time point (12 mo: ρ = 0.03, P = 0.46 and 24 mo: ρ = −0.02, P = 0.68).”
Quote in the paperNot a substantial claim - Study design and conductown data
Age-in-months was not correlated with IJA score within time point at 12 months.
“There was no effect of site on IJA scores (F = 0.97, P = 0.41), and age-in-months was not correlated with IJA score within time point (12 mo: ρ = 0.03, P = 0.46 and 24 mo: ρ = −0.02, P = 0.68).”
Quote in the paperNot a substantial claim - Premisecitation
Significant methodological challenges in imaging localized brain function that supports social behaviors in children during the first 2 years of life contribute to poor understanding of the neural substrates underlying IJA.
“The neural substrates underlying IJA in early childhood are poorly understood (Barak and Feng 2016), due in part to significant methodological challenges in imaging localized brain function that supports social behaviors in children during the first 2 years of life.”
Quote in the paperSubstantial claim - Study design and conductown data
The age groups did not differ by proportion of children later diagnosed with ASD.
“The age groups did not differ by proportion of children later diagnosed with ASD (Fisher's exact test, P = 0.29).”
Quote in the paperNot a substantial claim - Study design and conductown data
There was no effect of site on IJA scores.
“There was no effect of site on IJA scores (F = 0.97, P = 0.41), and age-in-months was not correlated with IJA score within time point (12 mo: ρ = 0.03, P = 0.46 and 24 mo: ρ = −0.02, P = 0.68).”
Quote in the paperNot a substantial claim - Premisecitation
Atypical development of the initiation of joint attention (IJA) is strongly indicative of autism spectrum disorder (ASD).
“In fact, early exhibition of joint attention is strongly associated with later language ability (Morales et al. 2000; Mundy et al. 2007), and atypical development of the initiation of joint attention (IJA) is strongly indicative of autism spectrum disorder (ASD) (Bruinsma et al. 2004).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bruinsma et al. 2004 source
Not checked in the free run.
- Premisecitation
Early exhibition of joint attention is strongly associated with later language ability.
“In fact, early exhibition of joint attention is strongly associated with later language ability (Morales et al. 2000; Mundy et al. 2007), and atypical development of the initiation of joint attention (IJA) is strongly indicative of autism spectrum disorder (ASD) (Bruinsma et al. 2004).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Initiating joint attention (IJA) emerges over the first 2 years of life.
“The emergence of joint attention (JA), the coordinated orienting of 2 people toward an object or event, occurs during the first 2 years of life, arguably the most dynamic and important period of early child development (Scaife and Bruner 1975).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Scaife and Bruner 1975
Not checked in the free run.
- Premisecitation
The neural substrates underlying IJA in early childhood are poorly understood.
“The neural substrates underlying IJA in early childhood are poorly understood (Barak and Feng 2016), due in part to significant methodological challenges in imaging localized brain function that supports social behaviors in children during the first 2 years of life.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Barak and Feng 2016
Not checked in the free run.
- Study design and conductown data
Age groups did not significantly differ by IQ (Mullen composite standard score).
“Age groups did not significantly differ by proportion of HR participants (P = 0.99), girls (P = 0.32), or IQ (Mullen composite standard score, t = −0.92, df = 687, P = 0.18).”
Quote in the paperNot a substantial claim - Study design and conductown data
Age groups did not significantly differ by proportion of HR participants.
“Age groups did not significantly differ by proportion of HR participants (P = 0.99), girls (P = 0.32), or IQ (Mullen composite standard score, t = −0.92, df = 687, P = 0.18).”
Quote in the paperNot a substantial claim - Study design and conductreasoning
This sample provided the range of behavior required to adequately test the brain-IJA relationships that we report.
“As such, this sample provided the range of behavior required to adequately test the brain-IJA relationships that we report.”
Quote in the paperSubstantial claim- Rests on an assumption: Infants with an older sibling with an ASD diagnosis (HR) are more than 10 times more likely to be diagnosed with ASD than infants without an older sibling or immediate relative with a positive ASD diagnosis (LR).
- Rests on an assumption: HR infants who do not develop autism will eventually show rates of more than 30% with other subthreshold (for autism) psychopathology.
- Study design and conductown data
No significant relationship was observed between resting-state motion parameters and IJA scores at 12 months.
“No significant relationship was observed (12 mo: mean FD before scrubbing ρ = 0.02, P = 0.81; max FD before scrubbing ρ = 0.02, P = 0.86; mean FD after scrubbing ρ = 0.04, P = 0.66; max FD after scrubbing ρ = 0.04, P = 0.70. 24 mo: mean FD before scrubbing ρ = −0.03, P = 0.74; max FD before scrubbing ρ = 0.06, P = 0.52; mean FD after scrubbing ρ = 0.06, P = 0.52; max FD after scrubbing ρ = 0.02, P”
Quote in the paperNot a substantial claim - Interpretationcitation
The shift in behavioral strategies may reflect maturation of connections between default mode network regions, known to be involved in hetero-modal integration and processing of socially relevant stimuli and interactions, with primary visual and sensory-motor regions along with higher association areas distributed throughout prefrontal and parietal cortex.
“This shift in behavioral strategies may reflect maturation of connections between default mode network regions, known to be involved in hetero-modal integration as well as processing of socially relevant stimuli and interactions, with primary visual and sensory-motor regions along with higher association areas distributed throughout the prefrontal and parietal cortex (Buckner et al. 2008; Fransson”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationcitation
The observed differences in functional network associations with increasing frequency of IJA across 12-24 months may reflect changes in functional connectivity driven by social experience-dependent learning over the second year of life and the unfolding, later transition from nonverbal to verbal communication.
“These observed differences in functional network associations with increasing frequency of IJA across 12–24 months may reflect changes in fc driven by social experience-dependent learning that occurs over the second year of life (Tomasello et al. 2005; Canals et al. 2009; Lewis et al. 2009; Fransson et al. 2011) and the unfolding, later transition from nonverbal to verbal communication (Morales et”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationown data
The more distributed strong correlations at 24 months reflect a different balance of brain function underlying the complex behavior of IJA.
“reflecting a different balance of brain function underlying the complex behavior of IJA.”
Quote in the paperSubstantial claim - Study design and conductown data
No significant relationship was observed between the amount of frames passing the FD threshold and IJA score at 12 months.
“Testing with a Spearman rank correlation found no significant relationship observed in the amount of frames passing the FD threshold and IJA score (12 mo: ρ = −0.5, P = 0.57 and 24 mo: ρ = −0.1, P = 0.89).”
Quote in the paperNot a substantial claim - Premisecitation
The underlying psychological and behavioral features of ASD are continuously distributed in the population.
“The underlying psychological and behavioral features of ASD are continuously distributed in the population (e.g., Constantino and Todd 2000; Constantino 2011; Constantino and Charman 2016).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
A negative brain-behavior correlation involving 12-month Vis-DAN ROIs means that as brain functional connectivity decreased, the frequency of IJA increased.
“To explain: negative brain-behavior correlation involving 12 mo Vis-DAN ROIs means that as the brain fc decreased, the frequency of IJA increased.”
Quote in the paperNot a substantial claim - Interpretationcitation
As functional connectivity values increased from zero to strong and positive, presumably reflecting a significant history of in-phase co-activation, the frequency of IJA increased.
“This means that as the fc values increased from zero to strong and positive, presumably reflecting a significant history of in-phase (coherent) co-activation (Lewis et al. 2009), the frequency of IJA increased.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Lewis et al. 2009 source
Not checked in the free run.
- Premisecitation
Head motion, even of submillimeter magnitude, is a nonphysiological source of spurious variance in resting-state fMRI data.
“Head motion, even of submillimeter magnitude, has been identified as a nonphysiological source of spurious variance in resting-state fMRI data (Power et al. 2012; Van Dijk et al. 2012; Satterthwaite et al. 2013).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
A positive brain-behavior correlation between Vis-pcDMN means that as brain functional connectivity increased, the frequency of IJA also increased.
“In contrast, positive brain-behavior correlation between Vis-pcDMN means that as the brain fc increased, the frequency of IJA also increased.”
Quote in the paperSubstantial claim - Study design and conductown data
The sample is too small to test for differences within age between risk or diagnostic groups.
“Though the sample is too small to test for differences within age between risk or diagnostic groups (Supplementary Table 1)”
Quote in the paperSubstantial claim - Study design and conductown data
The permutation-based false-positive-rate exhibited no correlation with the number of ROIs within a network pair.
“The permutation-based false-positive-rate exhibited no correlation with the number of ROIs within a network pair (Supplementary Fig. 2F,G).”
Quote in the paperNot a substantial claim - Interpretationown data
In network pairs implicated at 24 months but neither significantly enriched at 12 months nor different across age (aFPC-DAN, aFPC-aFPC, Sal-aDMN), the relationships of connections within the network pairs to IJA become strengthened over the second year of life.
“Similarly, in those network pairs implicated at 24 mo but neither significantly enriched at 12 mo nor different across age (i.e., aFPC-DAN P < 1.5 × 10−1, aFPC-aFPC P < 2.0 × 10−1, Sal-aDMN, P < 7.0 × 10−2), the relationships of the connections within the network pairs to IJA become strengthened over the second year of life.”
Quote in the paperSubstantial claim - Study design and conductown data
The distribution of IJA values in participants with fcMRI data was not significantly different from that of a larger sample population at 24 months.
“The distribution of IJA values in the participants for whom we had fcMRI data was not significantly different from that of a larger sample population (Mann–Whitney U test, 12 mo: n = 429, z = 0.60, P = 0.55; 24 mo: n = 384, z = 1.2, P = 0.24).”
Quote in the paperNot a substantial claim - Study design and conductown data
The distribution of IJA values in participants with fcMRI data was not significantly different from that of a larger sample population at 12 months.
“The distribution of IJA values in the participants for whom we had fcMRI data was not significantly different from that of a larger sample population (Mann–Whitney U test, 12 mo: n = 429, z = 0.60, P = 0.55; 24 mo: n = 384, z = 1.2, P = 0.24).”
Quote in the paperNot a substantial claim - Interpretationreasoning
The contributions of connections within the network pairs implicated at 12 months but not at 24 months to IJA become more muted over the second year of life.
“This reflects a more subtle difference wherein the contributions of the connections within the network pairs to IJA become more muted over the second year of life.”
Quote in the paperSubstantial claim - Interpretationown data
A history of strong antiphase co-activation (strong magnitude functional connectivity but negative in sign) correlated with fewer acts of IJA.
“In this case, a history of strong antiphase co-activation (i.e., strong magnitude fc but negative in sign) correlated with fewer acts of IJA.”
Quote in the paperSubstantial claim - Study design and conductown data
No significant relationship was observed between resting-state motion parameters and IJA scores at 24 months.
“No significant relationship was observed (12 mo: mean FD before scrubbing ρ = 0.02, P = 0.81; max FD before scrubbing ρ = 0.02, P = 0.86; mean FD after scrubbing ρ = 0.04, P = 0.66; max FD after scrubbing ρ = 0.04, P = 0.70. 24 mo: mean FD before scrubbing ρ = −0.03, P = 0.74; max FD before scrubbing ρ = 0.06, P = 0.52; mean FD after scrubbing ρ = 0.06, P = 0.52; max FD after scrubbing ρ = 0.02, P”
Quote in the paperNot a substantial claim - Study design and conductown data
No significant relationship was observed between the amount of frames passing the FD threshold and IJA score at 24 months.
“Testing with a Spearman rank correlation found no significant relationship observed in the amount of frames passing the FD threshold and IJA score (12 mo: ρ = −0.5, P = 0.57 and 24 mo: ρ = −0.1, P = 0.89).”
Quote in the paperNot a substantial claim - Interpretationown data
IJA is intimately and differentially related to the systems-level organization of the 12-month and 24-month developing brain.
“Here, we show that IJA is intimately and differentially related to the systems-level organization of the 12-mo and 24-mo developing brain.”
Quote in the paperSubstantial claim- Rests on an assumption: There is near complete absence of extant data about brain-behavior associations during the epoch of development studied (12–24 months).
- Interpretationreasoning
The observed varying brain-behavior relationships may relate to toddlers' increasing capacity to use multiple strategies to initiate joint attention.
“Additionally, these observed varying brain-behavior relationships may relate to the toddlers’ increasing capacity to use multiple strategies to initiate joint attention.”
Quote in the paperNot a substantial claim
- The quote only partly states this claim. 3
- May combine two claims. 18
- Classified as probably not a substantial claim. 24
The quote only partly states this claim.
Findingown dataThe strongest brain-behavior associations include connections between the visual network and dorsal attention network.
“In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe other network pairs implicated at 12 months (SMN2-aDMN, SMN2-SMN) were not significantly enriched at 24 months and did not yield different enough brain-behavior relationships to pass significance across age.
“while the other network pairs implicated at 12 mo were not significantly enriched at 24 mo (based on the χ2 and hypergeometric tests), they did not yield different enough brain-behavior relationships to pass significance across age (McNemar brain-wide FPR; SMN2-aDMN P < 1.1 × 10−1, SMN2-SMN P < 2.1 × 10−1).”
Quote in the paperSubstantial claimMay combine two claims. The quote only partly states this claim.
Findingown dataAcross subjects, individual brain-behavior correlations between IJA scores and fcMRI for each of 26,335 ROI pairs were of moderate magnitude, and none passed Bonferroni correction for multiple comparisons.
“Individual brain-behavior correlations were of a moderate magnitude; none passed Bonferroni correction for multiple comparisons.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataDifferent sets of implicated networks were found at each age, with the strongest associations between visual and dorsal attention networks and between the visual network and parietal aspects of the default mode network at 12 months.
“We found different sets of implicated networks at each age, with the strongest associations between visual and dorsal attention networks and between the visual network and parietal aspects of the default mode network at 12 months.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe current results reveal that specific network pairs exhibiting the strongest associations with IJA within age as well as the strongest differences across age include Vis-DAN and Vis-pcDMN in the 12-month age group.
“The current results reveal that specific network pairs exhibiting the strongest associations with IJA within age as well as the strongest differences across age include the Vis-DAN and the Vis-pcDMN in the 12-mo age group.”
Quote in the paperSubstantial claim- Rests on an assumption: There is near complete absence of extant data about brain-behavior associations during the epoch of development studied (12–24 months).
May combine two claims.
Findingown dataAt 12 months, strong positive brain-behavior correlations were apparent in connections of ROIs between the Vis-pcDMN, and the functional connectivity between those ROIs was also generally positive.
“For example, at 12 mo, strong positive brain-behavior correlations were apparent in connections of ROIs between the Vis-pcDMN (Fig. 3), and the fc between those ROIs was also generally positive (orange and yellow lines in Fig. 4).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAlthough functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations are clustered within connections between a small subset of functional brain networks.
“In particular, we found that though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations are clustered within connections between a small subset of functional brain networks.”
Quote in the paperSubstantial claim- Rests on an assumption: There is near complete absence of extant data about brain-behavior associations during the epoch of development studied (12–24 months).
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataAt 12 months, there was no relationship between the number of ROI pairs within a network pair and the brain-wide false-positive rejection rate.
“number of ROI pairs within a network pair and the brain-wide FPR rate at 12 mo (n = 91, χ2, Pearson r = −0.15, P < 1.6 × 10−1; hypergeometric, r = −0.19, P < 7.5 × 10−2; Supplementary Fig. 2F)”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataA highly similar pattern emerges from both infant-toddler and adult network models: IJA is correlated with brain functional connectivity between regions distributed throughout the cerebrum, with the strongest brain-behavior correlations clustered into a specific and small number of functional network pairs that are different across the age groups.
“In general, a highly similar pattern emerges from both the infant–toddler and adult network models: IJA is correlated with brain fc between regions distributed throughout the cerebrum, with the strongest brain-behavior correlations clustered into a specific and small number of functional network pairs that are different across the age groups.”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataIJA scores increased from 12 to 24 months.
“The 12 -mo infants and 24-mo toddlers exhibited markedly different amounts of spontaneous IJA behavior; the distribution in IJA scores reflected the emergence of IJA over the second year of life with the expected large age-related increase in IJA (Wilcoxon signed-rank test, z = −11.8, P < 3.4 × 10−32) (Fig. 1B).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataFour of the 7 adult-functional network pairs contain significantly different brain-behavior relationships across age, including one enriched at 24 months (VAN-DMN).
“Additionally, 4 of the 7 adult-functional network pairs contain significantly different brain-behavior relationships across age, including one enriched at 24 mo (VAN-DMN).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataAge groups did not significantly differ by proportion of girls.
“Age groups did not significantly differ by proportion of HR participants (P = 0.99), girls (P = 0.32), or IQ (Mullen composite standard score, t = −0.92, df = 687, P = 0.18).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationEngaging in joint attention lays the foundation for empathy.
“It is theorized that engaging in JA lays the foundation for prosocial cooperative behavior, from basic social-communicative functioning and language development (Premack 2004) to sophisticated forms of empathy (Mundy and Jarrold 2010) and theory of mind (Adolphs 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Mundy and Jarrold 2010
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationEngaging in joint attention lays the foundation for basic social-communicative functioning and language development.
“It is theorized that engaging in JA lays the foundation for prosocial cooperative behavior, from basic social-communicative functioning and language development (Premack 2004) to sophisticated forms of empathy (Mundy and Jarrold 2010) and theory of mind (Adolphs 2003).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Premack 2004 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationEngaging in joint attention lays the foundation for theory of mind.
“It is theorized that engaging in JA lays the foundation for prosocial cooperative behavior, from basic social-communicative functioning and language development (Premack 2004) to sophisticated forms of empathy (Mundy and Jarrold 2010) and theory of mind (Adolphs 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Adolphs 2003 source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductnone givenAll data sets were subject to stringent fcMRI quality control criteria and IBIS Network behavioral and structural MRI inclusion criteria.
“All data sets were subject to stringent fcMRI quality control criteria and Infant Brain Imaging Study (IBIS) Network behavioral and structural MRI inclusion criteria.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductnone givenThe fcMRI data were acquired while participants were naturally sleeping, and sleep stage was not monitored with EEG polysomnography.
“Another limitation of the current study is that the fcMRI data were acquired while the participants were naturally sleeping and sleep stage was not monitored with EEG polysomnography.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable).
Interpretationnone givenThese observations offer a first glimpse into the functional brain structure underlying the emergence and consolidation of IJA across the second year of life.
“In summary, these observations offer a first glimpse into the functional brain structure underlying the emergence and consolidation of IJA across the second year of life.”
Quote in the paperNot a substantial claim- Rests on an assumption: There is near complete absence of extant data about brain-behavior associations during the epoch of development studied (12–24 months).
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenOne limitation of the current study is that the ROIs derive from work in older subjects.
“One limitation is that the ROIs derive from work in older subjects.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
InterpretationreasoningThe infant-toddler-derived networks better reflect the developing brain's functional architecture for these infant-toddler brain-behavior correlation analyses than the adult networks.
“presumably, because our infant–toddler-derived networks better reflect the developing brain's functional architecture for these infant–toddler brain-behavior correlation analyses”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe study was not designed or powered to address questions about differences between high- and low-risk groups.
“However, our study was not designed or powered to address these questions.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningPotential differences in sleep stage may exist both within and between the age groups, complicating interpretation of the fcMRI data.
“Potential differences in sleep stage may exist both within and between the age groups, complicating interpretation of the fcMRI data.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductcitationThe ROIs used in the current study are well defined and have been used in the literature in typical and autism-related studies.
“The ROIs used in the current study are well defined and have been used in the literature in typical and autism-related studies (Pruett et al. 2015), and offer a foundation for the current analysis.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Pruett et al. 2015 source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationThe permutation test provides control over family-wise error rate, is nonparametric, automatically adjusts to the degree of correlation between tests, and does not make specific assumptions about the shape of the population distribution.
“The permutation test provides control over family-wise error rate, is nonparametric, automatically adjusts to the degree of correlation between tests, and does not make specific assumptions about the shape of the population distribution from which the observations have been derived (Backes et al. 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Backes et al. 2014 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
Study design and conductnone givenAn additional limitation of the study is the potential for differences in brain-behavior relationships between high- and low-risk groups both within and across age, including the possibility that the network architecture underlying IJA may differ in children who develop ASD.
“An additional limitation of the study is the potential for differences in brain-behavior relationships between high- and low-risk groups both within and across age, including the possibility that the network architecture underlying IJA may differ in children who develop ASD.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThese results may inform clinical therapies by providing further physiological foundation for JA-based behavior interventions that have been shown to significantly improve outcome in children with ASD.
“These results may inform clinical therapies by providing further physiological foundation for JA-based behavior interventions that have been shown to significantly improve outcome in children with ASD (Kasari et al. 2012; Chahrour et al. 2016).”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim. May combine two claims.
PremisecitationPrevious task-based studies in infants using PET or EEG indicated that IJA may be supported by prefrontal areas, while adult fMRI and eye-tracking studies implicated a distributed set of regions throughout prefrontal, temporal, and parietal cortices.
“Previous foundational task-based studies in infants using positron emission tomography (PET) (Caplan et al. 1993) or electroencephalography (EEG) (Mundy et al. 2000; Henderson et al. 2002), indicated that IJA may be supported by prefrontal areas, while groundbreaking studies in adults using novel fMRI and eye tracking paradigms (Redcay et al. 2012; Caruana et al. 2015) implicated a distributed set”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll participants contributed exactly 150 frames clean for analyses.
“In the end, all participants contributed exactly 150 frames clean for analyses.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenWe did not track if participants arrived to the scanning session awake or for how long they had been asleep.
“We did not track if participants arrived to the scanning session awake or alternatively for how long they had been asleep.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAcquiring fMRI data during natural sleep provides potential insight into a population that is generally challenging to study.
“Acquiring fMRI data during natural sleep provides potential insight into a population that generally is challenging to study (Dehaene-Lambertz et al. 2002; Redcay et al. 2007; Graham et al. 2015; Pruett et al. 2015).”
Quote in the paperNot a substantial claim0 of 3 sources checkedClassified as probably not a substantial claim. May combine two claims.
Study design and conductnone givenStringent data quality control procedures minimized the presence of signal contamination due to motion-induced artifacts and ensured at least 6.25 min of high-quality MRI data.
“Stringent data quality control procedures minimized the presence of signal contamination due to motion-induced artifacts and ensured at least 6.25 min of high-quality MRI data.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductcitationIJA behavior was assessed with the CSBS-DP, which is designed to elicit social and communicative behaviors in infants and toddlers between 12 and 24 months of age.
“IJA behavior was assessed at IBIS Network clinical sites with the Communication and Symbolic Behavioral Scales-Developmental Profile (CSBS-DP) (Wetherby et al. 2002), which is designed to elicit social and communicative behaviors in infants and toddlers between 12 and 24 months of age (Fig. 1B).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wetherby et al. 2002 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Study design and conductreasoningThe sleep stages of participants during functional MRI scans may be more variable than if all participants arrived awake.
“The sleep stages of the participants while they were undergoing their functional MRI scans may be more variable than if all participants arrived awake.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenADOSs and all other testing and interview data were independently reviewed by experienced clinicians for DSM-IV-TR criteria.
“ADOSs and all other testing and interview data were independently reviewed by experienced clinicians for DSM-IV-TR (American Psychiatric Association 2000) criteria for autistic disorder or pervasive developmental disorder not otherwise specified.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenAssessments were video recorded and scored by research-reliable expert raters to ensure accuracy and intersite and intrasite reliability across the IBIS network.
“Assessments are video recorded and scored by research-reliable expert raters to ensure accuracy and intersite and intrasite reliability across the IBIS network.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThese regions reflect a broad integrated set of regions that support coordinated functioning of vision, attention, task control, and-along with subcortical and cingulate regions-motivation and reward signals.
“These regions reflect a broad integrated set of regions that support the coordinated functioning of vision, attention, task control, and—along with subcortical and cingulate regions (Schilbach et al. 2010; Pfeiffer et al. 2014; Oberwelland et al. 2016)—motivation and reward signals.”
Quote in the paperNot a substantial claim0 of 3 sources checked
The authors state this as an assumption.
IJA behaviors may serve different functions at different ages.
“Because we expect IJA behaviors to potentially serve different functions at different ages, we do not necessarily expect to observe a downward extension of the adult or school-aged participant findings to infants and toddlers.”
The paper relies on this without support.
Children at high familial risk for ASD carry a familial liability typically associated with behaviors such as impaired IJA, subthreshold to a full autism diagnosis, but distributed along a continuum.
“Children at high risk for developing ASD carry a familial liability typically associated with behaviors, such as impaired IJA, subthreshold to a full autism diagnosis, but distributed along a continuum.”
The paper relies on this without support.
The adult-derived ROI parcellation and network naming are applicable to infants and toddlers.
“ROIs (n = 280) were adopted from a combination of task data and cortical functional areal parcellations (Cohen et al. 2008) obtained in healthy adults (Power et al. 2011), and meta-analyses of autism studies (Philip et al. 2012).”
The paper relies on this without support.
There is near complete absence of extant data about brain-behavior associations during the epoch of development studied (12–24 months).
“Because of near complete absence of extant data about brain-behavior associations during this epoch of development”
The paper relies on this without support.
Infants with an older sibling with an ASD diagnosis (HR) are more than 10 times more likely to be diagnosed with ASD than infants without an older sibling or immediate relative with a positive ASD diagnosis (LR).
“Infants with an older sibling with an ASD diagnosis (HR) are >10× more likely to be diagnosed with the disorder than infants without an older sibling or immediate relative with a positive ASD diagnosis (LR).”
The paper relies on this without support.
HR infants who do not develop autism will eventually show rates of more than 30% with other subthreshold (for autism) psychopathology.
“In addition, those HR infants who do not develop autism will eventually show rates of >30% with other traits subthreshold (for autism) psychopathology.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cognitive capacities change together with network-level effects inside and across resting-state networks over postnatal development.
“specific cognitive capacities co-evolve with complex network effects within and between different RSNs, throughout postnatal development”
From Development of large-scale functional networks from birth to adulthood: A guide to the neuroimaging literature (2017) · cites this paper as Eggebrecht et al., 2017
A recent study using matched methods in adults and 1-2 year olds first directly showed many localized infant modules and how they map onto adult organization.
“One recent report compared community structure in adults against that in 1–2 year olds using closely matched methods (Eggebrecht et al., 2017), providing the first direct evidence for numerous anatomically localized modules in the infant brain and their relationship to adult functional organization (Figure 2C).”
From Development of large-scale functional networks from birth to adulthood: A guide to the neuroimaging literature (2017) · cites this paper as Eggebrecht et al., 2017
The ANOVA chi-squared analysis may be underpowered and is not definitive.
“We would like to emphasize that the ANOVA chi-squared analysis may be underpowered 88 and, though enticing, is not definitive.”
From Subtyping cognitive profiles in Autism Spectrum Disorder using a Functional Random Forest algorithm (2018) · cites this paper as [88]
The study had sufficient power to examine the effect of ASD on resting state data but was underpowered when examining differences between subgroups.
“While we had sufficient power to examine the effect of ASD on resting state data 88, we were underpowered when examining differences between subgroups.”
From Subtyping cognitive profiles in Autism Spectrum Disorder using a Functional Random Forest algorithm (2018) · cites this paper as [88]
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- Consistentz = 0.6reported p = .55 · recomputed p = .549
“z = 0.60, p = .55”
- Consistentz = 1.2reported p = .24 · recomputed p = .230
“z = 1.2, p = .24”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
A 130-frame fMRI run does not last 6.25 minutes
MinorAt the stated repetition time of 2500 ms, 130 frames take 325,000 ms, or about 5.42 minutes. The reported 6.25 minutes would require 150 frames.
Reported 6.25 · recomputed 325000
“Functional images were collected as a gradient-echo echo planar image (TE = 27 ms, TR = 2500 ms, voxel size 4 × 4 × 4 mm3, flip angle 90°, field of view 256 mm, matrix 64 × 64, bandwidth 1906 Hz). All included infants provided at least 2 fMRI runs, each run comprising 130 temporally contiguous frames (6.25 min).”
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- Authors
- Eggebrecht, A. T., Elison, J. T., Feczko, E., Todorov, A., Wolff, J. J., Kandala, S., Adams, C. M., Snyder, A. Z., Lewis, J. D., Estes, A. M., Zwaigenbaum, L., Botteron, K. N., McKinstry, R. C., Constantino, J. N., Evans, A., Hazlett, H. C., Dager, S., Paterson, S. J., Schultz, R. T., Styner, M. A., Gerig, G., Das, S., Kostopoulos, P., The IBIS Network, Schlaggar, B. L., Petersen, S. E., Piven, J., & Pruett, J. R.
- Affiliations
- Washington University in St. Louis (US)
- University of Minnesota (US)
- Oregon Health & Science University (US)
- Montreal Neurological Institute and Hospital (CA)
- University of Washington (US)
- University of Alberta (CA)
- University of North Carolina at Chapel Hill (US)
- Children's Hospital of Philadelphia (US)
- New York University (US)
- Corresponding author
- Eggebrecht, Adam T
- ORCID
- Eggebrecht, Adam T
- Elison, Jed T
- Feczko, Eric
- Wolff, Jason J
- Kandala, Sridhar
- Snyder, Abraham Z
- Lewis, John D
- Estes, Annette M
- Zwaigenbaum, Lonnie
- Botteron, Kelly N
- McKinstry, Robert C
- Constantino, John N
- Evans, Alan
- Hazlett, Heather C
- Dager, Stephen
- Paterson, Sarah J
- Schultz, Robert T
- Styner, Martin A
- Gerig, Guido
- Das, Samir
- Schlaggar, Bradley L
- Petersen, Steven E
- Piven, Joseph
- Pruett, John R
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-01-07
- Volume
- 27
- Issue
- 3
- Pages
- 1709-1720
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC5452276
- OpenAlex
- W2569374490
- Semantic Scholar
- 6c455646823b927efcdfa6424a751288ad60d80a
- Cited by
- 156
- References
- 76
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 14 · 2023: 16 · 2022: 20 · 2021: 19 · 2020: 13 · 2019: 16 · 2018: 18 · 2017: 6
- FWCI
- 8.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cerebral Cortex (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (K01-MH103594, R01-MH093510, K01-MH101653, P30-NS048056, U54-HD087011)
- National Institute Of Child Health & Human Development
- Intellectual and Developmental Disabilities Research Center
- Autism Center of Excellence award (#HD055741)
- McDonnell Center for Systems Neuroscience
- Autism Speaks (#6020)
- Simons Foundation (#140209)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Developmental and Educational Psychology › Child and Animal Learning Development
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- joint attention, brain functional connectivity, infants, toddlers, autism spectrum disorder, social communication development, visual network, dorsal attention network, default mode network, posterior cingulate cortex, brain-behavior relationship, social behavior development, neurodevelopmental disorders
- MeSH terms
- Attention, Brain, Brain Mapping, Child Development, Psychology, Child, Child, Preschool, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Neural Pathways, Neuropsychological Tests
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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