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Cited by 226Functional Brain Connectivity StudiesAdvanced Neuroimaging Techniques and ApplicationsCognitive Abilities and Testing

Imaging Patterns of Brain Development and their Relationship to Cognition

Open access
Erus, G., Battapady, H., Satterthwaite, T. D., Hakonarson, H., Gur, R. E., Davatzikos, C., Gur, R. C.·2015·Cerebral Cortex
DOI 10.1093/cercor/bht425PMC PMC4428302
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Abstract

We present a brain development index (BDI) that concisely summarizes complex imaging patterns of structural brain maturation along a single dimension using a machine learning methodology. The brain was found to follow a remarkably consistent developmental trajectory in a sample of 621 subjects of ages 8-22 participating in the Philadelphia Neurodevelopmental Cohort, reflected by a cross-validated correlation coefficient between chronologic age and the BDI of r = 0.89. Critically, deviations from this trajectory related to cognitive performance. Specifically, subjects whose BDI was higher than their chronological age displayed significantly superior cognitive processing speed compared with subjects whose BDI was lower than their actual age. These results indicate that the multiparametric imaging patterns summarized by the BDI can accurately delineate trajectories of brain development and identify individuals with cognitive precocity or delay.

AI snapshot

Written from the paper’s full text.

TL;DR

The paper derives a brain development index (BDI) from multimodal structural and diffusion MRI using support vector regression, showing that imaging patterns predict chronological age in youths aged 8–22 with cross-validated r = 0.89. Deviations of BDI from chronological age relate to cognitive performance, especially processing speed, with advanced-BDI subjects showing superior speed compared with delayed-BDI subjects.

Key findings

  • In 621 subjects aged 8–22, the combined T1 and DTI model predicted chronological age with cross-validated r = 0.89 and mean absolute error (MAE) = 1.22 years.
  • Single-modality models were less accurate: ADC r = 0.85, MAE = 1.35; FA r = 0.83, MAE = 1.41; GM r = 0.81, MAE = 1.52; WM r = 0.76, MAE = 1.71; ventricular maps r = 0.43, MAE = 2.71.
  • Sex-specific models performed comparably: males trained on males r = 0.87, MAE = 1.291; females trained on females r = 0.88, MAE = 1.264. Applying the male model to females overestimated chronological age in females, especially younger ages, while the female model underestimated male chronological ages, most noticeably in younger ages.
  • Cognitive comparisons among advanced (n = 22), delayed (n = 31), and normal (n = 165) BDI groups showed significant group differences primarily in speed, with the most significant effect for motor speed (MOT q = 0.004); memory-domain speed tests were also significant (VMEM q = 0.008, FMEM q = 0.005, SMEM q = 0.031). Accuracy showed a significant group difference only for abstraction and mental flexibility (ABF q = 0.029).

Methods

  • Participants were drawn from the Philadelphia Neurodevelopmental Cohort (PNC). Of 1078 interim subjects, 457 were excluded for insufficient data quality (n = 240) or history suggesting potential brain development abnormalities (n = 217), leaving 621 subjects aged 8–22 years (351 female; mean age 15.08 years, SD 3.27).
  • T1-weighted MPRAGE and DTI images were processed into GM, WM, and ventricular RAVENS maps plus FA and ADC maps. The concatenated feature vector contained 1,116,006 features. A linear-kernel support vector regression (LIBSVM) with 10-fold cross-validation was used to estimate the BDI.
  • Cognitive performance was measured with the Penn Computerized Neurocognitive Battery (14 tests; accuracy and speed z-scored by age bin). Outliers were defined as subjects beyond the 90% confidence interval from the BDI–age regression (advanced or delayed), and normal subjects were within a 30% prediction interval. One-way ANOVA compared cognitive scores across groups, with false discovery rate correction.

Limitations

  • The paper states that its scope was relatively limited and focused on relating cognitive development to structural brain changes; it also notes that the SVR weight maps do not provide a measure directly comparable across different image maps and that future work will use multikernel learning.
  • The paper reports that when groups were formed using only ADC or ADC and TR, group differences were consistent in direction but not significant after FDR correction (q > 0.05).
  • Evident from the text: the study is cross-sectional across ages 8–22, so it cannot directly track within-person developmental trajectories; many subjects were excluded for data quality or potential abnormalities, which may limit generalizability; cognitive assessment occurred on average 3.4 months after neuroimaging; and the advanced and delayed groups were small (n = 22 and n = 31), which may limit power for cognitive comparisons.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/cercor/bht425

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 22 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    When the model was applied within each sex separately, it achieved comparable accuracy.

    “When the method was applied in each sex independently, a comparable accuracy was obtained”
    Quote in the paperSubstantial claim
  • Findingown data

    The model captured the developmental trajectory of the brain, as shown by a cross-validated correlation of r = 0.89 between chronological age and the BDI.

    “The developmental trajectory of the brain has been successfully captured by this model, as reflected by a crossvalidated correlation coefficient between chronologic age and the BDI of r = 0.89.”
    • Also stated in: § Discussion · plain
      “The correlation between the chronological age and the BDI is r = 0.89.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Deviation of BDI from chronological age indicates advanced or delayed brain maturation.
  • Findingnone given

    Lateral ventricle volume increased linearly with age.

    “Lateral ventricle volume increases linearly with age.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In 621 subjects aged 8-22 from the Philadelphia Neurodevelopmental Cohort, the BDI and chronological age correlated at r = 0.89 under cross-validation.

    “The brain was found to follow a remarkably consistent developmental trajectory in a sample of 621 subjects of ages 8-22 participating in the Philadelphia Neurodevelopmental Cohort, reflected by a cross-validated correlation coefficient between chronologic age and the BDI of r = 0.89.”
    • Also stated in: § BDI · plain
      “When all image maps were used in combination as input samples, a high estimation accuracy was obtained, with r = 0.89 correlation between the BDIs and the chronological ages of subjects (10-fold cross-validated, as described in Materials and methods).”
    Quote in the paperSubstantial claim
  • Findingown data

    The male-specific model predicted age in males with r = 0.87 and MAE = 1.291.

    “The prediction accuracy for both sexes were comparable to the accuracy obtained using all subjects together (r = 0.87 and MAE = 1.291 for males trained on males, and r = 0.88 MAE = 1.264 for females trained on females).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 30
  • Classified as probably not a substantial claim. 10
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    For speed scores, all three memory-domain tests had significant FDR-corrected q values, whereas cognition-domain tests did not.

    “All 3 tests in memory domain had significant q value for speed, while the q values for tests in cognition domain were not significant.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The BDI groups do not differ systematically on factors other than brain maturation that could affect cognitive performance.

  • May combine two claims.

    Findingown data

    According to the male model, female subjects had higher BDI in early ages and lower BDI at ages 16-21.

    “According to the MM, female subjects have a higher BDI compared with what the MM expected in the early ages, and a lower BDI in ages ranging from 16-21.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Cortical gray matter volume decreased consistently with age from 8 to 22, with region-specific patterns.

    “We observe a consistent decrease in GM volume with age in the whole brain, with region specific patterns of maturation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Contrary to expectations, both advanced and delayed BDI groups performed less accurately on the abstraction and mental flexibility domain and on the complex cognition domains of language and nonverbal reasoning.

    “Contrary to our expectations, both the advanced and delayed groups performed less accurately on the abstraction and mental flexibility domain, as well as on the complex cognition domains of language and nonverbal reasoning.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The BDI groups do not differ systematically on factors other than brain maturation that could affect cognitive performance.

  • May combine two claims.

    Findingown data

    Using the VN map alone, age prediction had r = 0.43 and MAE = 2.71.

    “WM maps obtained a lower r value (r = 0.76, MAE = 1.71), and the BDIs obtained using VN maps had relatively much lower correlation with the chronological ages (r = 0.43, MAE = 2.71).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The three BDI groups differed significantly in speed scores, with the strongest effect in the motor speed (MOT) test.

    “Notably, we observed significant group differences in speed, the most significant effect being observed in motor speed (MOT) test.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The BDI groups do not differ systematically on factors other than brain maturation that could affect cognitive performance.

  • May combine two claims.

    Findingreasoning

    In the sample, global white matter volume increased with age while global gray matter volume decreased.

    “globally, the WM volume increases while the GM volume decreases, as a result of both progressive myelination and regressive pruning processes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Male-based BDI scores overestimated chronological age in females, especially in younger age groups, and female-based BDI scores underestimated male chronological age, again most noticeably in younger age groups.

    “Specifically, as predicted, BDI scores based on males overestimated chronological age in females, especially in the younger age groups, while female-based BDI scores underestimated male chronological ages, again most noticeably in the younger age groups.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Deviation of BDI from chronological age indicates advanced or delayed brain maturation.

  • May combine two claims.

    Findingown data

    Models using single image maps predicted age successfully, but the highest accuracy came from combining voxel-wise features from all image maps.

    “While the models using single image maps were also successful in predicting age, the highest accuracy was obtained by the combination of voxel-wise features from all image maps.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Using the FA map alone, age prediction had r = 0.83 and MAE = 1.41.

    “However the r value was still high, particularly for the ADC (r = 0.85, MAE = 1.35),FA (r = 0.83, MAE = 1.41), and GM (r = 0.81, MAE = 1.52) maps.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    When groups were defined using only ADC or ADC and TR, the group differences in speed were consistent with the main findings (advanced group higher speed) but were not significant after FDR correction.

    “In both cases the groups displayed differences consistent with the previous findings, with advanced group showing a higher performance in speed, however, the group differences were not significant after FDR correction (i.e., q > 0.05).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The BDI groups do not differ systematically on factors other than brain maturation that could affect cognitive performance.

  • May combine two claims.

    Findingown data

    According to the female model, male subjects had lower BDI than female subjects in early ages but closed the gap later.

    “According to the MF, male subjects have a lower BDI than the female subjects in the early ages, but they close the gap in later ages.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Using the GM map alone, age prediction had r = 0.81 and MAE = 1.52.

    “However the r value was still high, particularly for the ADC (r = 0.85, MAE = 1.35),FA (r = 0.83, MAE = 1.41), and GM (r = 0.81, MAE = 1.52) maps.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Using the ADC map alone, age prediction had r = 0.85 and MAE = 1.35.

    “However the r value was still high, particularly for the ADC (r = 0.85, MAE = 1.35),FA (r = 0.83, MAE = 1.41), and GM (r = 0.81, MAE = 1.52) maps.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the study sample, all three BDI groups showed similar patterns of gray matter maturation, but maturation occurred earlier in the advanced BDI group and later in the delayed BDI group than in the normal group.

    “We observed a maturational shift between the groups, such that all groups demonstrated similar patterns of maturation, but they occurred earlier in the advBDI group and later in the delBDI group.”
    • Also stated in: § Discussion · plain
      “A consistent developmental pattern is observed for all groups similar to that shown in Figure1.However a shift can be observed between the 3 groups, where the GM decrease happens earlier in the advanced group, and later in the delayed group, compared with normal group.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Cross-sectional age differences in the sample reflect developmental changes over time.

  • May combine two claims.

    Findingown data

    Gray matter volume decreases with age across the whole brain, with region-specific patterns of maturation.

    “The GM volume decreases with age in the whole brain, with region specific patterns of maturation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Advanced versus delayed maturation effects appear exclusive to speed of performance, while both can adversely affect performance on tasks requiring more extensive cortical resources.

    “It appears that advanced compared with delayed maturation effects are exclusive for speed of performance, whereas both can adversely affect performance on tasks that require more extensive cortical resources.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The BDI groups do not differ systematically on factors other than brain maturation that could affect cognitive performance.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Luna and Sweeney (2001) emphasized the need to characterize normal development before studying at-risk or clinical populations, specifically for understanding dysmaturation in schizophrenia.

    “Luna and Sweeney (2001) emphasized the need for neurobehavioral and neuroimaging studies characterizing normal development before examining at-risk or clinical populations, referring specifically to elucidation of dysmaturation processes in schizophrenia.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Luna and Sweeney 2001

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Jung and Haier (2007), reviewing 37 neuroimaging studies, reported a consensus that individual differences in intelligence test scores relate to variations in brain structure and function.

    “Reviewing 37 neuroimaging studies, Jung and Haier (2007) reported a striking consensus on findings that relate individual differences in intelligence test scores to variations in brain structure and function.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Jung and Haier 2007

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The RAVENS approach has been extensively validated and applied in various studies.

    “The RAVENS approach has been extensively validated and applied in various studies (Resnick et al. 2000;Beresford et al. 2006;Gur et al. 2006;Driscoll et al. 2009).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Resnick et al. 2000 source

      Not checked in the free run.

    • cites Beresford et al. 2006 source

      Not checked in the free run.

    • cites Gur et al. 2006

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The results supported the hypotheses and provided novel evidence that individual differences in complex brain development patterns affect cognitive functioning.

    “As described below, results supported our hypotheses, providing novel evidence that individual differences in complex patterns of brain development have an impact on cognitive functioning.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: BDI values outside the prediction interval represent true advanced or delayed brain development rather than measurement error.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Image quality was verified with automated and manual QA at each processing step, and 240 images that failed QA were removed.

    “The quality of the initial and processed images were verified using strictly defined quality control procedures involving both automated and manual QA at each step of processing; images (n = 240) that failed QA procedures at any stage were removed from the analysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The results indicate that multiparametric imaging patterns summarized by the BDI can accurately delineate brain development trajectories and identify cognitive precocity or delay.

    “These results indicate that the multiparametric imaging patterns summarized by the BDI can accurately delineate trajectories of brain development and identify individuals with cognitive precocity or delay.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: BDI values outside the prediction interval represent true advanced or delayed brain development rather than measurement error.

  • May combine two claims.

    Interpretationreasoning

    Precocious maturers may over-apply speed, hindering accuracy on tasks requiring reflection and computation, whereas delayed maturers may lack cerebral resources for accurate performance and thus be both slow and inaccurate.

    “Precocious maturers may over-apply speed that can hinder accuracy on tasks that require reflection and computation, while delayed maturers may lack the cerebral resources for accurate performance and are hence both slow and inaccurate.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The neurocognitive effects show greater maturational effects on speed than on accuracy, consistent with prior studies on age-related performance changes.

    “The neurocognitive effects indicate greater maturational effects on speed than accuracy, which is consistent with multiple studies on age-related changes in performance across the lifespan (Kail 2007;Coyle et al. 2011).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Kail 2007 source

      Not checked in the free run.

    • cites Coyle et al. 2011

      Not checked in the free run.

    • Rests on an assumption: The BDI groups do not differ systematically on factors other than brain maturation that could affect cognitive performance.

  • May combine two claims.

    Study design and conductnone given

    The SVR weight maps are informative about the relative contribution of specific brain regions to the regression hyperplane, but they cannot directly compare different image maps.

    “We should note that, while being informative on the relative contribution of specific brain regions to the regression hyperplane, the w maps do not provide a measure that could be directly used to compare different image maps.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Developmental increases in speed of information processing reflect a distinct process from accuracy development, which also matures but more slowly during adolescence.

    “Notably, the developmental increases in speed of information processing reflected a distinct process from the development of accuracy, which also matures albeit at a slower slope than speed (Gur et al. 2012) during adolescence.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gur et al. 2012

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Gogtay et al. (2004) reported accelerated frontal lobe maturation during adolescence and related it to increased executive function effectiveness.

    “Gogtay et al. (2004)reported accelerated maturation of frontal lobe during adolescence and related it to increased effectiveness of executive functions.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gogtay et al. 2004

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Study design and conductnone given

    Ten-fold cross-validation provides an unbiased estimate of model predictive accuracy and prevents over-fitting.

    “This procedure provides an unbiased estimate of model predictive accuracy and prevents model over-fitting.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Study procedures were reviewed and approved by the Institutional Review Boards of Penn and CHOP.

    “Study procedures were reviewed and approved by the Institutional Review Boards of both Penn and CHOP.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    The mechanisms leading to poorer accuracy may differ between the two groups.

    “The path to poorer accuracy could be different for the 2 groups.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    Multiple testing correction using false discovery rate estimation was applied, with adjusted P values (q-values) reported.

    “Multiple testing correction using false discovery rate (FDR) estimation is applied using the method described in Storey (2002) and adjusted P values (q-values) are reported.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Storey (2002)

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The quantitative results indicate that the different image maps contribute complementary information but also have some redundancy in information content.

    “These quantitative results point to the contribution of complementary information from each of these different maps, but also to a certain redundancy in their information content.”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Study design and conductown data

    The final sample comprised 621 subjects aged 8-22 years (351 female), mean age 15.08 years (SD 3.27), after exclusions for insufficient data quality or potential brain development abnormalities.

    “The final sample included 621 subjects aged 8-22 years (351 female); mean age 15.08 years (3.27 standard deviation [SD]).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Bachman et al. (2012) reported that adolescent-onset psychosis patients do not show normal age-related increases in processing speed, which predicts poorer functional outcomes.

    “It is noteworthy that Bachman et al. (2012) reported that adolescent-onset psychosis patients fail to show normal age-related increases in processing speed, which in turn predicts poorer functional outcomes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bachman et al. 2012 source

      Not checked in the free run.

35 of 35

  • The paper relies on this without support.

    Patterns of brain change during development are distributed throughout the whole brain rather than localized to specific regions.

    “patterns of brain change during development are spread throughout the whole brain, and are not localized in specific regions”

  • The authors state this as an assumption.

    Chronological age is a ground truth for brain development.

    “as a subject's age is a ground truth that is easily ascertained”

  • The paper relies on this without support.

    BDI values outside the prediction interval represent true advanced or delayed brain development rather than measurement error.

    “Outliers having a BDI higher than the prediction interval boundaries are referred to as advanced (advBDI), and those having a BDI lower than the prediction interval boundaries here are called delayed (delBDI).”

  • The paper relies on this without support.

    Deviation of BDI from chronological age indicates advanced or delayed brain maturation.

    “The subjects outside the 90% prediction interval have been labeled as outliers (advanced or delayed brain development).”
    “The subjects in the advance (advBDI), delayed (delBDI), and normally-developed (normBDI) groups were determined based on their BDIs calculated using the model trained on all subjects and all image maps (Fig. 2).”

  • The paper relies on this without support.

    Cross-sectional age differences in the sample reflect developmental changes over time.

    “To emphasize the differences between the 3 groups, we visualized the dynamic changes through age for subjects in each group, by creating average GM RAVENS within consecutive age intervals between age 8 and 22 (Fig. 5).”
    “We observed a maturational shift between the groups, such that all groups demonstrated similar patterns of maturation, but they occurred earlier in the advBDI group and later in the delBDI group.”

  • The paper relies on this without support.

    The BDI groups do not differ systematically on factors other than brain maturation that could affect cognitive performance.

    “We compared the cognitive performance of the subjects in the 3 groups, by applying a one-way ANOVA between groups for each test score.”
6 of 6

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?

  • ALL survivors in late childhood or adolescence may face unique challenges associated with ongoing brain maturation processes.

    “Secondly, ALL survivors in late childhood or adolescence may be faced with unique challenges associated with ongoing brain maturation processes (Erus et al., 2015).”

    From Brain structure, working memory and response inhibition in childhood leukemia survivors (2017) · cites this paper as Erus et al., 2015

    The Introduction states that healthy brain maturation continues through childhood and adolescence, and the Discussion says cognitive processes continue to mature in adolescence. The Participants section describes a youth sample that excluded individuals with medical histories potentially affecting brain function; the paper does not establish that ALL survivors face unique challenges from these processes. Page numbers are unavailable in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Regional differences in developmental time course are likely to alter regional sensitivity to chemotherapy and its long-term impact.

    “For instance, regional differences in developmental time course (e.g., protracted development of the frontal lobes) (Erus et al., 2015; Zatorre, Fields, & Johansen‐Berg, 2012) are likely to alter regional sensitivity to chemotherapy and its long‐term impact.”

    From Brain structure, working memory and response inhibition in childhood leukemia survivors (2017) · cites this paper as Erus et al., 2015

    The Introduction states that brain regions follow temporally distinct maturational trajectories, supporting the claim of regional differences in developmental time course. The Discussion mentions frontal-lobe maturation during adolescence but does not establish the specific example of protracted frontal-lobe development. The chemotherapy implication follows the citations as the citing authors’ inference, rather than a finding attributed to this source. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Our approach has advantages over existing approaches to normative modeling based on multivariate regression and the one-class support vector machine.

    “Moreover, our approach has advantages over existing approaches to normative modeling based on multivariate regression (18) and the one-class support vector machine (15).”

    From Understanding heterogeneity in clinical cohorts using normative models: Beyond case-control studies (2016) · cites this paper as [18]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Opposite directions reported for cross-sex age predictions

    Minor

    The stated prediction says male-trained models underestimate age in females and female-trained models overestimate age in males. The Discussion says the observed effects run in the opposite directions, while describing them as predicted.

  • Outlier boundary called both a confidence and a prediction interval

    Minor

    The methods define outliers using a 90% confidence interval band around the regression, whereas the figure caption says the boundary is a 90% prediction interval. These are different intervals and would generally identify different outliers.

2 of 2

Cites

Flagged first, then by citations

1 of the 50 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. 2011, ACM TRANS INTELL SYST TECHNOL, 2, 1
  2. 2011, 12, 2211
  3. 2006, Schizophrenia Bulletin, 31, 408
  4. 2007, NeuroImage, 36, 1965

Cited by

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Related

Authors
Erus, G., Battapady, H., Satterthwaite, T. D., Hakonarson, H., Gur, R. E., Davatzikos, C., & Gur, R. C.
Affiliations
  • University of Pennsylvania (US)
  • Children's Hospital of Philadelphia (US)
Corresponding author
Erus, G.
ORCID
Venue
Cerebral Cortex
Publisher
Oxford University Press (OUP)
Published
2014-01-12
Volume
25
Issue
6
Pages
1676-1684
ISSN
  • 1047-3211 (ISSN-L)
  • 1460-2199
DOI
10.1093/cercor/bht425
PMC
PMC4428302
OpenAlex
W2166109328
Semantic Scholar
964ac4e4c7284adb72198db681d006487fde3c53
Cited by
226
References
50
Citations by year
2026: 9 · 2025: 16 · 2024: 19 · 2023: 20 · 2022: 19 · 2021: 23 · 2020: 20 · 2019: 27 · 2018: 17 · 2017: 18 · 2016: 18 · 2015: 16 · 2014: 4
FWCI
10.33
Type
journal article
Language
en
Open access
Locations
  • Cerebral Cortex (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • U.S. Public Health Service (NIA-R01-14971)
  • National Institute on Aging
  • National Institute of Mental Health (RC2MH089983, MH089983, K23MH098130, MH089924, RC2MH089924, MH019112, T32MH019112)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD086984)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
Keywords
developmental trajectories, processing speed, cognitive delay, Philadelphia Neurodevelopmental Cohort, neuroimaging biomarkers
MeSH terms
Adolescent, Aging, Brain, Brain Mapping, Child, Cognition, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Regression Analysis, Cohort Studies, Young Adult

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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 2026-10-08.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.

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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