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Cited by 105Functional Brain Connectivity StudiesNeural and Behavioral Psychology StudiesAdvanced Neuroimaging Techniques and Applications

Developmental sex differences in resting state functional connectivity of amygdala sub-regions

Open access
Alarcón, Gabriela, Cservenka, Anita, Rudolph, Marc D., Fair, Damien A., Nagel, Bonnie J.·2015·NeuroImage
DOI 10.1016/j.neuroimage.2015.04.013PMC PMC4461484
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Abstract

During adolescence, considerable social and biological changes occur that interact with functional brain maturation, some of which are sex-specific. The amygdala is one brain area that has displayed sexual dimorphism, specifically in socio-affective (superficial amygdala [SFA]), stress (centromedial amygdala [CMA]), and learning and memory (basolateral amygdala [BLA]) processing. The amygdala has also been implicated in mood and anxiety disorders which display sex-specific features, most prominently observed during adolescence. Using functional magnetic resonance imaging (fMRI), the present study examined the interaction of age and sex on resting state functional connectivity (RSFC) of amygdala sub-regions, BLA and SFA, in a sample of healthy adolescents between the ages 10 and 16 years (n = 122, 71 boys). Whole-brain, voxel-wise partial correlation analyses were conducted to determine RSFC of bilateral BLA and SFA seed regions, created using the Eickhoff-Zilles maximum probability maps based on cytoarchitectonic mapping and FMRIB's Integrated Registration and Segmentation Tool (FIRST). Monte Carlo simulation was implemented to correct for multiple comparisons (threshold of 53 contiguous voxels with a z-value ≥ 2.25). Results indicated that with increasing age, there was a corresponding decrease in RSFC between both amygdala sub-regions and parieto-occipital cortices, with a concurrent increase in RSFC with medial prefrontal cortex (mPFC). Specifically, boys and girls demonstrated increased coupling of mPFC and left and right SFA with age, respectively; however, neither sex showed increased connectivity between mPFC and BLA, which could indicate relative immaturity of fronto-limbic networks that is similar across sex. A dissociation in connectivity between BLA- and SFA-parieto-occipital RSFC emerged, in which girls had weaker negative RSFC between SFA and parieto-occipital regions and boys had weaker negative RSFC of BLA and parieto-occipital regions with increased age, both standing in contrast to adult patterns of amygdala sub-regional RSFC. The present findings suggest relative immaturity of amygdala sub-regional RSFC with parieto-occipital cortices during adolescence, with unique patterns in both sexes that may support memory and socio-affective processing in boys and girls, respectively. Understanding the underlying normative functional architecture of brain networks associated with the amygdala during adolescence may better inform future research of the neural features associated with increased risk for internalizing psychopathology.

AI snapshot

Written from the paper’s full text.

TL;DR

This fMRI study tested whether age and sex interact in resting-state functional connectivity of basolateral and superficial amygdala subregions in 122 healthy adolescents aged 10–16. It reports sex-specific developmental shifts in amygdala coupling with parieto-occipital and medial prefrontal regions, suggesting different maturational timing for BLA- and SFA-based networks.

Key findings

  • Across age, both BLA and SFA showed weaker connectivity with parieto-occipital cortices and stronger connectivity with mPFC, but the direction of change differed by sex.
  • Girls showed a shift from positive to negative BLA–parieto-occipital connectivity with age, whereas boys showed the reverse, with both shifting around age 14; for SFA–parieto-occipital connectivity, boys became more negative and girls more positive with age.
  • mPFC coupling was lateralized by sex: boys showed increased left SFA–left vmPFC connectivity with age, while girls showed increased right SFA–dmPFC connectivity; neither sex showed increased mPFC–BLA coupling.
  • Adding puberty as a covariate did not significantly change the connectivity results (all r² ≥ 0.52, p ≤ 0.001).

Methods

  • Cross-sectional sample of 122 adolescents (71 boys), ages 10–16, without current DSM-IV psychiatric disorders, significant substance use, neurological illness, or other exclusionary conditions; scanned at 3T with two resting-state fMRI runs.
  • Amygdala subregion ROIs were defined by intersecting Eickhoff-Zilles maximum probability maps with FIRST-based segmentation; BLA and SFA were analyzed, while CMA was excluded because many participants had zero or very few CMA voxels (BLA mean voxel count 905.1 ± 232.4; SFA 180.8 ± 85.6; CMA 0.9 ± 2.2).
  • Whole-brain voxel-wise partial correlations modeled age, sex, sex-by-age, and residual framewise displacement; Monte Carlo correction used 53 contiguous voxels at z ≥ 2.25. Post-hoc models added puberty as a covariate.

Limitations

  • The paper states that the cross-sectional design cannot capture developmental change or causal effects, that CMA could not be reliably analyzed, that the puberty measure had only modest agreement with clinician or Tanner assessments, and that a supplementary motion-censoring analysis was consistent but some effects became trend-like.
  • The paper also notes the lack of adult comparison data, which limits conclusions about whether the observed adolescent patterns represent immature or transitional connectivity.
  • Evident from the text: the sample is healthy and restricted to ages 10–16, and the authors describe behavioral and clinical interpretations as speculative because no direct behavioral or psychopathology outcomes were tested.

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

Integrity signals

Registry

Crossref · 10.1016/j.neuroimage.2015.04.013

Cites

86 of 86 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 92 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    After data scrubbing, age remained negatively correlated with framewise displacement remaining mean.

    “but age was still negatively correlated with FD (r2 = −0.31, p = 0.001);”
    Quote in the paperSubstantial claim
  • Findingown data

    Connectivity between the left superficial amygdala and ventromedial prefrontal cortex followed the same patterns seen in basolateral amygdala connectivity with cortical regions.

    “Connectivity between left SFA and vmPFC followed the patterns observed in RSFC of BLA with cortical brain regions.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Before data scrubbing, framewise displacement values did not differ statistically between boys and girls.

    “Prior to data scrubbing, FD values were statistically similar in boys and girls (t120 = −1.91, p = 0.06)”
    Quote in the paperNot a substantial claim
  • Findingown data

    Boys showed increased coupling between similar regions with age, shifting from negative to positive connectivity around age 14.

    “On the other hand, boys showed increased coupling between similar regions with age, with a shift from negative to positive connectivity, also around the age of 14 years.”
    Quote in the paperSubstantial claim
  • Findingown data

    After data scrubbing, there were no sex differences in framewise displacement remaining mean.

    “Following data scrubbing, there were no sex differences in FD (i.e. FD remaining mean) (t120 = 0.27, p = 0.79),”
    Quote in the paperSubstantial claim
  • May combine two claims. 46
  • Classified as probably not a substantial claim. 31

  • May combine two claims.

    Findingown data

    In the left superficial amygdala, a sex-by-age interaction was observed in the right lingual gyrus, left superior frontal gyrus, right cuneus, and right culmen; in all these regions except the left ventromedial prefrontal cortex, girls showed increased positive connectivity with age and boys showed increased negative connectivity with age.

    “In left SFA an interaction was seen in right lingual gyrus (LG), left SFG, right cuneus and right culmen, and in all these regions, except left vmPFC, girls had increased positive connectivity with age, and boys had increased negative connectivity with age.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Boys showed increased positive connectivity with age between the left superficial amygdala and left ventromedial prefrontal cortex, while girls showed increased positive connectivity between the right superficial amygdala and a more dorsal medial prefrontal region.

    “Specifically, increased positive connectivity between left SFA and left vmPFC with age was observed in boys, while girls showed increased positive connectivity between right SFA and a more dorsal mPFC region.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the left basolateral amygdala, a sex-by-age interaction was observed in the left inferior parietal lobule and right angular gyrus, with boys showing increased positive connectivity with age and girls showing increased negative connectivity with age.

    “In left BLA, an interaction of sex and age was seen in left inferior parietal lobule (IPL) and right angular gyrus (AG) that displayed the pattern described above: increased positive connectivity with age in boys and increased negative connectivity with age in girls.”
    Quote in the paperSubstantial claim

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

    Findingown data

    Voxel counts did not differ statistically between sexes for any amygdala sub-region.

    “Further, voxel counts were not statistically different by sex for any sub-region (all t120 < 0.48, p > 0.05).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Based on voxel counts, the basolateral amygdala was larger in the left hemisphere than in the right.

    “BLA size, based on voxel count, was larger in left compared to right hemisphere (t120 = 33.41, p < 0.001),”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The analysis revealed a dissociation in basolateral amygdala resting-state functional connectivity: girls had positive connectivity at younger ages that decreased into negative connectivity over adolescence, while boys had negative connectivity at younger ages that increased into positive connectivity.

    “This examination revealed a dissociation of RSFC of BLA, in which girls had positive RSFC at younger ages that decreased over adolescent development into negative RSFC, while boys had negative RSFC at younger ages that increased over development to positive RSFC.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the right superficial amygdala, connectivity with the left postcentral gyrus followed the same patterns as basolateral amygdala connectivity, while connectivity with the left dorsomedial prefrontal cortex showed the opposite pattern, with girls increasing in positive connectivity with age and boys increasing in negative connectivity with age.

    “Finally, in right SFA, connectivity with left postcentral gyrus also followed the same patterns of RSFC observed with BLA, while connectivity with left dorsomedial PFC (dmPFC) showed the opposite pattern, with girls having increased positive connectivity with age and boys having increased negative connectivity with age (Figures 1-3 and Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    With increasing age, boys showed coupling between the ventromedial prefrontal cortex and basolateral amygdala, while girls showed coupling between the dorsomedial prefrontal cortex and superficial amygdala.

    “Rather, with age, boys showed coupling between vmPFC and BLA, while girls showed coupling between dmPFC and SFA,”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The findings are specific to the superficial amygdala and lateralized by sex, with connections to different medial prefrontal regions.

    “Our findings are specific to SFA and lateralized by sex, with functional connections to different regions of the mPFC.”
    Quote in the paperSubstantial claim

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

    Findingown data

    The right superficial amygdala had a larger voxel count than the left superficial amygdala.

    “while right SFA voxel count was larger than left SFA (t120 = −10.71, p < 0.001).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Boys and girls did not differ statistically in age, IQ, or socioeconomic status.

    “Boys and girls did not differ statistically by age, IQ or SES, but did differ in pubertal development, although on average, boys and girls reported the same pubertal stage (see Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At younger ages, girls had more positive connectivity between the basolateral amygdala and posterior-occipital cortex, which decreased to negative connectivity by age 14, indicating increased decoupling with age.

    “Specifically, at younger ages, girls had more positive RSFC between BLA and posterior-occipital cortex that diminished to negative connectivity by the age of 14 years, reflecting increased decoupling of these regions with age.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Although the groups were not matched on pubertal status, a post-hoc examination showed that this maturational difference did not statistically affect the results.

    “Although the groups were not matched on pubertal status, the effect of puberty was examined post-hoc, and this maturational gap did not statistically affect the results of the present analyses.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Boys and girls differed in pubertal development, but on average they reported the same pubertal stage.

    “but did differ in pubertal development, although on average, boys and girls reported the same pubertal stage (see Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Both superficial and basolateral amygdala sub-regions showed decreased connectivity with parieto-occipital cortices and increased connectivity with the medial prefrontal cortex.

    “Both SFA and BLA sub-regions showed decreased connectivity with parieto-occipital cortices and increased connectivity with mPFC,”
    Quote in the paperSubstantial claim

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

    Findingown data

    The basolateral amygdala regions had the largest average voxel counts (905.1 ± 232.4), followed by superficial amygdala (180.8 ± 85.6) and centromedial amygdala (0.9 ± 2.2), consistent with anatomical size.

    “On average, BLA ROIs had larger voxel counts (905.1 ± 232.4), followed by SFA (180.8 ± 85.6) and CMA (0.9 ± 2.2), corresponding to anatomical size.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Most centromedial amygdala voxel counts were very small, and many were zero.

    “However, most CMA voxel counts were quite small and in many cases zero, so we chose not to include CMA ROIs in functional connectivity analyses.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    With age, boys showed stronger negative connectivity, while girls showed more positive connectivity between the superficial amygdala and parieto-occipital cortex.

    “The opposite pattern was observed with functional connectivity of SFA and parieto-occipital brain regions: with age, boys had more robust negative RSFC, while girls had more positive RSFC between SFA and parieto-occipital cortex.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    With increasing age, boys showed more mature decoupling between the superficial amygdala and parieto-occipital cortex than girls, who showed immature functional coupling between these regions.

    “With increasing age, boys also displayed more mature decoupling of SFA and parieto-occipital cortex, compared to girls who showed immature functional coupling between these regions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The supplementary robustness analysis was consistent with the reported findings, although some findings remained trend-like and did not reach significance, potentially due to reduced power.

    “The results of this analysis show consistency with the reported findings, albeit some findings, potentially due to reduced power, remained trend like and did not reach significance.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Most participants had zero voxels confidently corresponding to the centromedial amygdala (48% left, 100% right), and those with voxels had between one and ten.

    “many participants had CMA ROIs with as little as one voxel and as many as ten corresponding to this region; the majority of participants had zero voxels that confidently corresponded to the CMA (48% in left CMA and 100% in right CMA).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Girls showed more mature decoupling between the basolateral amygdala and parieto-occipital cortical regions than boys, who showed immature functional coupling between these areas.

    “Conversely, girls had more mature decoupling of BLA and parieto-occipital cortical regions, while boys showed immature functional coupling between these same areas.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The centromedial amygdala is essential for producing behavioral responses through projections to the brainstem, striatum, and cortical regions.

    “The CMA is critical in the generation of behavioral responses through projections to the brainstem, striatum, and regions of the cortex (LeDoux, 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites LeDoux, 2003 source

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

    Premisecitation

    During adolescence, medial prefrontal and rostral anterior cingulate cortex do not effectively down-regulate amygdalar function, which can lead to heightened emotional reactivity as described by the Dual Systems Model.

    “As such, it is believed that amygdalar functioning is not down-regulated effectively by medial prefrontal cortex (mPFC) and rostral anterior cingulate cortex (rACC) during adolescence (i.e. Dual Systems Model), which can manifest as heightened emotional reactivity typical of this developmental period (Hare et al., 2008, Perlman and Pelphrey, 2011, McRae et al., 2012, Gee et al., 2013).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Hare et al., 2008 source

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    • cites Perlman and Pelphrey, 2011

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    • cites McRae et al., 2012 source

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

    Premisecitation

    The superficial amygdala is involved in olfactory and affective processing.

    “Finally, the SFA is relevant for olfactory (Price, 2003, Heimer and Van Hoesen, 2006) and affective processes (Bzdok et al., 2013a).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Price, 2003 source

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    • cites Heimer and Van Hoesen, 2006

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    • cites Bzdok et al., 2013a

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  • May combine two claims.

    Premisecitation

    The amygdala is composed of basolateral, centromedial, and superficial nuclei, which have distinct functional connections to the cortex and support different brain functions.

    “The amygdala can be subdivided into basolateral (BLA), centromedial (CMA) and superficial (SFA) nuclei, each with distinct functional connections to the cortex supporting different brain functions.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites LeDoux, 2003 source

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    • cites Price, 2003 source

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    • cites Amunts et al., 2005 source

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

    Premisecitation

    The basolateral amygdala supports associative learning, such as fear conditioning, through inputs from the frontal cortex and other subcortical areas.

    “The BLA facilitates associative learning processes, like fear conditioning, through afferent projections from the frontal cortex and other subcortical regions (LeDoux, 2003, Phelps and LeDoux, 2005).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites LeDoux, 2003 source

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    • cites Phelps and LeDoux, 2005 source

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  • Classified as probably not a substantial claim.

    Study design and conductown data

    Because a residual correlation remained between framewise displacement remaining mean and age, framewise displacement remaining mean was included as a covariate in the resting-state functional connectivity analyses.

    “Due to a residual correlation between FD remaining mean and age, this variable was included as a covariate in the analyses (see 3. Results).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Other studies have shown that prefrontal cortical development continues through adolescence, with girls showing greater maturity than boys.

    “while different studies have also shown protracted prefrontal cortical development through adolescence, with girls showing relative maturity as compared to boys (Giedd et al., 1996, Lenroot et al., 2007).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Giedd et al., 1996 source

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    • cites Lenroot et al., 2007 source

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    Interpretationcitation

    These findings align with the Dual Systems Model, which proposes that top-down regulation of the limbic system by the medial prefrontal cortex increases with age, though the regional specificity slightly differs.

    “These findings are in line with the Dual Systems Model that posits increasing top-down regulation of the limbic system via mPFC with age (Galvan et al., 2006, Steinberg, 2010); however, the regional specificity of the present findings slightly deviate from this model.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Galvan et al., 2006 source

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    • cites Steinberg, 2010 source

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    Premisecitation

    In prefrontal cortices, girls reach peak gray matter volume approximately two years earlier than boys.

    “as well as in prefrontal cortices, with girls peaking in gray matter volume approximately two years earlier than boys (Lenroot et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lenroot et al., 2007 source

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

    Premisecitation

    Atypical functional connectivity between the amygdala and medial prefrontal cortex underlies impaired emotional and cognitive function in schizophrenia, bipolar disorder, and mood disorders.

    “Furthermore, atypical functional connectivity of amygdala-mPFC neurocircuitry has been shown to underlie disrupted emotional and cognitive ability during psychopathologic states, such as schizophrenia, bipolar disorder, and mood disorders (Anand et al., 2005, Das et al., 2007, Henry et al., 2008, Wang et al., 2009, Berking and Wupperman, 2012, Cisler and Olatunji, 2012),”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Anand et al., 2005 source

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    • cites Das et al., 2007

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    • cites Henry et al., 2008 source

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  • May combine two claims.

    Interpretationown data

    Girls and boys showed opposing connectivity patterns that only partly resemble adult connectivity between parieto-occipital cortices and amygdala sub-regions, with superficial amygdala connectivity appearing more mature in girls and basolateral amygdala connectivity more mature in boys.

    “Girls and boys exhibited opposing RSFC connectivity patterns that only partially reflect adult functional connectivity of parieto-occipital cortices with sub-regions of the amygdala, in which SFA RSFC is more mature in girls, while BLA RSFC is more mature in boys.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Prior research has identified distinct resting-state functional connectivity patterns across amygdalar nuclei, with age-related positive connectivity to ventromedial prefrontal, temporal, and subcortical regions and negative connectivity to parietal and occipital cortices.

    “Previous work has found distinct functional connectivity patterns, as measured with RSFC, across amygdalar nuclei (Roy et al., 2009, Li et al., 2012, Qin et al., 2012, Gabard-Durnam et al., 2014), specifically different patterns of age-dependent positive connectivity between amygdalar nuclei and ventromedial PFC (vmPFC), temporal, and subcortical regions, as well as negative connectivity with pari”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Roy et al., 2009 source

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    • cites Li et al., 2012

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    • cites Qin et al., 2012 source

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    Premisecitation

    DVAR values vary across datasets for various reasons, which effectively removes the need for a standard threshold.

    “DVAR values, which are based in BOLD signal intensity, differ across datasets for a variety of reasons (e.g. blurring kernel size, frequency filter or data acquisition characteristics) (Power et al., 2014), effectively eliminating the need for a standard threshold.”
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    • cites Power et al., 2014 source

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    Study design and conductcitation

    Self-reported Pubertal Development Scale scores correlate moderately with other measures of pubertal status, such as Tanner's Sexual Maturation Scale.

    “Self-report on the PDS has been shown to correlate moderately with other measurements of pubertal status, like Tanner's Sexual Maturation Scale (Bond et al., 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bond et al., 2006 source

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  • Classified as probably not a substantial claim.

    Premisecitation

    Earlier studies have reported that connectivity between the medial prefrontal cortex and all amygdala sub-regions increases with age.

    “Previous research has shown coupling of mPFC and all amygdala sub-regions with increasing age (Roy et al., 2009, Qin et al., 2012, Gabard-Durnam et al., 2014),”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Roy et al., 2009 source

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    • cites Qin et al., 2012 source

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    • cites Gabard-Durnam et al., 2014 source

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    Study design and conductown data

    No demographic variables had absolute skewness or kurtosis values above 2.0, so they were treated as normally distributed.

    “No variables exceeded absolute skew/kurtosis values of 2.0, and thus were considered normally distributed.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Prior studies in adults have found sex differences in the shape and volume of amygdala sub-regions and in resting-state functional connectivity of non-limbic brain regions.

    “Previous studies in adults have reported sex differences in amygdala sub-region shape and volume (Kim et al., 2011, Kim et al., 2012) and in RSFC of non-limbic brain regions using a variety of analytic methods (Kilpatrick et al., 2006, Biswal et al., 2010, Tian et al., 2011, Casanova et al., 2012, Satterthwaite et al., 2014).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Kim et al., 2011 source

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    • cites Kim et al., 2012 source

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    • cites Kilpatrick et al., 2006 source

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    Premisecitation

    Only one previous study conducted a secondary analysis of sex differences in adolescents, and it did not find a significant effect of sex.

    “However, only one study performed a secondary analysis to examine sex differences in adolescents, which did not yield a significant effect of sex (Gabard-Durnam et al., 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gabard-Durnam et al., 2014 source

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

    Study design and conductcitation

    The study tested the robustness of its findings by adjusting functional connectivity processing steps and using a different motion-censoring method in a supplementary analysis.

    “we tested the robustness of our findings by adjusting the functional connectivity processing steps and employing a different method of motion censoring in a supplementary analysis (see Supplementary Methods), as suggested by prior reports (Hallquist et al., 2013, Power et al., 2014).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Hallquist et al., 2013 source

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    • cites Power et al., 2014 source

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  • May combine two claims.

    Interpretationown data

    The results indicate a sex-specific dissociation in resting-state functional connectivity between amygdala sub-regions and cortical regions, highlighting the importance of studying sex differences in adolescents and amygdala function by sub-region, potentially in socio-emotional processing and depression risk populations.

    “Overall, these results indicate a sex-specific dissociation in amygdala sub-region RSFC with cortical brain regions, which underscores the importance of both the examination of sex differences in adolescent samples and of amygdalar function by sub-region, potentially in the contexts of socio-emotional processing and with populations at risk for, or suffering from, depression.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Functional decoupling of the superficial amygdala and parietal cortex is relevant for social communication and behavior, but behavioral outcomes may differ by sex.

    “demonstrating that functional decoupling of SFA and parietal cortex is relevant for social communication and behavior, but that behavioral outcomes may differ depending on sex.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Research in rodents and humans has distinguished dorsal and ventral medial prefrontal cortex, with general agreement that dorsomedial prefrontal cortex supports cognitive processing while ventromedial prefrontal cortex supports emotional processing or internally directed activity.

    “Many studies in rodents and humans have functionally differentiated the dorsal and ventral mPFC, and there is general concensus that dmPFC supports cognitive processing, while vmPFC supports more emotional processing (Euston et al., 2012, Bzdok et al., 2013b) or internally-directed activity (Raichle et al., 2001).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Euston et al., 2012 source

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    • cites Bzdok et al., 2013b

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    • cites Raichle et al., 2001 source

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    Interpretationreasoning

    The current sample's age range of 10 to 16 years is more representative of adolescence, so the absence of connectivity between the medial prefrontal cortex and basolateral amygdala may suggest that fronto-limbic connectivity during adolescence is primarily supported by connectivity between the medial prefrontal cortex and superficial amygdala.

    “The age range of the current sample (10-16 years) is more representative of the adolescent period, therefore he lack of RSFC between mPFC and BLA may also suggest that fronto-limbic connectivity is primarily supported by RSFC between mPFC and SFA during adolescence.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The ventromedial prefrontal cortex is part of the ventral affective system in the Dual Systems Model, which proposes an imbalance between affective and cognitive control regions that leads to ineffective top-down regulation of affect by cognitive control.

    “The vmPFC is a component of the “ventral affective system” described in the Dual Systems Model, which posits an imbalance in access to affective versus cognitive control brain regions leading to ineffective top-down regulation of the affective system by the cognitive control system (Steinberg, 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Steinberg, 2010 source

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  • May combine two claims.

    Premisecitation

    The superficial amygdala is the most conserved amygdala sub-region and is thought to be important for social communication via olfactory and social cues.

    “The SFA is the most conserved amygdala sub-region and it is thought to play an important role in social communication via olfactory (Bzdok et al., 2013a) and social cues (Goossens et al., 2009, Bzdok et al., 2013a);”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Bzdok et al., 2013a

      Not checked in the free run.

    • cites Goossens et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A study found that allopregnanolone administration reduced connectivity between the amygdala and parietal cortex, and this reduction correlated with decreased negative affect.

    “A different study showed that administration of allopregnanolone reduced connectivity between the amygdala and parietal cortex, which was also correlated with reductions in negative affect (Sripada et al., 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sripada et al., 2014 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing). May combine two claims.

    Interpretationcitation

    If decoupling between the superficial amygdala and parieto-occipital cortices is the adult norm, then the sex-specific trajectories of amygdala sub-region connectivity seen in this adolescent sample may shift toward mature adult patterns.

    “If decoupling of SFA and parieto-occipital cortices is indeed the norm in adulthood as some studies suggest (Roy et al., 2009, Gabard-Durnam et al., 2014), then the sexually dimorphic trajectories of amygdala sub-regional connectivity observed in the current sample may give way to mature patterns observed in adults;”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Roy et al., 2009 source

      Not checked in the free run.

    • cites Gabard-Durnam et al., 2014 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Previous research on resting-state functional connectivity of amygdala sub-regions found that positive connectivity between all sub-regions and the medial prefrontal cortex increases with age from 10 to 25 years.

    “Previous research examining RSFC of amygdala sub-regions found increased positive connectivity with age (10 – 25 years) between all sub-regions and the mPFC (Gabard-Durnam et al., 2014),”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gabard-Durnam et al., 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The amygdala has positive connectivity with subcortical and limbic regions, and connectivity between these regions stabilizes early in childhood.

    “These and other studies suggest that the amygdala is positively connected with subcortical and limbic regions, and that functional connectivity between these brain regions is stabilized early in childhood development (Gabard-Durnam et al., 2014);”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gabard-Durnam et al., 2014 source

      Not checked in the free run.

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

    Premisecitation

    A recent meta-analytic connectivity modeling study found that ventromedial prefrontal cortex is primarily involved in bottom-up, approach/avoidance, and evaluation-related processing, while dorsomedial prefrontal cortex is mostly involved in top-down and metacognition-related processing in social cognition.

    “A recent study comparing dmPFC and vmPFC function with meta-analytic connectivity modeling found that vmPFC is primarily involved in bottom-up, approach/avoidance, and evaluation-related processing, while dmPFC was mostly involved in top-down and metacognition-related processing in social cognition (Bzdok et al., 2013b).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bzdok et al., 2013b

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Because the basolateral amygdala and medial prefrontal cortex showed no coupling, the current sample may show some immaturity in fronto-limbic connectivity.

    “Due to the lack of coupling between BLA and mPFC, the current sample may be displaying some immaturity in fronto-limbic connectivity.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    The study's cross-sectional design is not ideal for capturing developmental effects.

    “An additional limitation of this study is its cross sectional design, which is not ideal for capturing developmental effects.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    The study's large sample, careful delineation of amygdala sub-regions, and thorough head-motion assessment and scrubbing support confidence in the reported results.

    “The large sample size, careful delineation of amygdala sub-regions, and meticulous assessment of head motion and subsequent data scrubbing (see 2.4 Motion Correction and Supplementary Data) inspires confidence in the reported results.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Delayed maturation of cognitive control regions favors emotional processing by the amygdala and ventromedial prefrontal cortex in early adolescence, but with increasing age and maturity, cognitive control regions such as dorsolateral and dorsomedial prefrontal cortex regulate limbic regions more effectively.

    “The relatively delayed maturation of cognitive control regions favors emotional processing by regions like the amygdala and vmPFC in early adolescence; however, with increasing age and maturity, cognitive control brain regions like dorsolateral PFC and dmPFC more effectively regulate limbic regions.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Steinberg, 2010 source

      Not checked in the free run.

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

    Interpretationcitation

    Males with positive resting-state functional connectivity between parieto-occipital regions and the basolateral amygdala may have memory problems, because the basolateral amygdala is important for memory in addition to emotional processing.

    “Although all sub-regions are relevant for emotional processing (Ball et al., 2007, Hurlemann et al., 2008, Bzdok et al., 2013a), BLA is additionally important for memory function (Bzdok et al., 2013a); therefore, males demonstrating positive RSFC between parieto-occipital and BLA may report problems with memory functions.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Ball et al., 2007 source

      Not checked in the free run.

    • cites Hurlemann et al., 2008 source

      Not checked in the free run.

    • cites Bzdok et al., 2013a

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    The study's puberty measure has only modest concordance with clinician evaluations of pubertal girls and moderate agreement with self-reported Tanner staging, limiting interpretation of true pubertal effects.

    “Lastly, our measure of puberty shares only modest concordance with clinician evaluations of pubertal girls (Brooks-Gunn et al., 1987), which we did not have access to, and a moderate agreement with self-reported Tanner staging (Bond et al., 2006), limiting our interpretation of true pubertal effects.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Brooks-Gunn et al., 1987 source

      Not checked in the free run.

    • cites Bond et al., 2006 source

      Not checked in the free run.

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

    Premisecitation

    The medial prefrontal cortex is strongly implicated in social cognition and shows functional segregation along a dorsal-ventral axis.

    “The mPFC has been strongly implicated in social cognition and also displays functional segregation along the dorsal-ventral axis (Amodio and Frith, 2006, Pfeifer and Allen, 2012, Bzdok et al., 2013b);”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Amodio and Frith, 2006 source

      Not checked in the free run.

    • cites Pfeifer and Allen, 2012 source

      Not checked in the free run.

    • cites Bzdok et al., 2013b

      Not checked in the free run.

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

    Interpretationreasoning

    An alternative interpretation is that resting-state functional connectivity between the superficial amygdala and both ventral and dorsal medial prefrontal cortex supports different components of social cognition.

    “An alternative interpretation is that RSFC between SFA and both ventral and dorsal mPFC support different components of social cognition.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Prior studies show that during adolescence different brain regions reach peak gray matter volume at different rates, with concurrent neurophysiological changes.

    “Previous studies have shown that throughout the span of adolescence, different brain regions reach peak gray matter volume at distinct rates (Giedd, 2004, Gogtay et al., 2004, Creze et al., 2014), with concurrent changes in neurophysiology (Whitford et al., 2007).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Giedd, 2004 source

      Not checked in the free run.

    • cites Gogtay et al., 2004 source

      Not checked in the free run.

    • cites Creze et al., 2014 source

      Not checked in the free run.

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

    Interpretationcitation

    Girls may use the cuneus and lingual gyrus, which are involved in emotional face processing, for socio-emotional processing as a distinct mechanism supporting connectivity patterns that manifest as sexually dimorphic social behavior.

    “Alternatively, girls may rely on regions such as the cuneus and LG, which are implicated in emotional face processing (Bremner et al., 2004, Kitada et al., 2010, Kret et al., 2011), for socio-emotional processing as a distinct mechanism supporting neural functional connectivity patterns that in turn manifest into sexually dimorphic social behavior.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bremner et al., 2004 source

      Not checked in the free run.

    • cites Kitada et al., 2010 source

      Not checked in the free run.

    • cites Kret et al., 2011 source

      Not checked in the free run.

62 of 62

  • The paper relies on this without support.

    Cytoarchitectonic maps based on adult samples may not be representative of adolescent populations.

    “Although cytoarchitectonic maps are precise microstructural tools, they are based on adult samples that may not be representative of adolescent populations.”

  • The paper relies on this without support.

    An imbalance in maturity of frontal and limbic brain regions is likely insufficient to explain the range of behavior in adolescents.

    “An imbalance in maturity of frontal and limbic brain regions is likely insufficient, however, to explain the range of behavior in adolescents.”

  • The paper relies on this without support.

    Sex differences may be obscured when collapsing data across a variety of developmental stages.

    “however, sex differences may be obscured when collapsing data across a variety of developmental stages.”
3 of 3

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?

  • Some studies show more focal sex differences in the thalamus, corpus callosum, cingulum, and superior cerebellar peduncles, and some show regions of increased FA in adult females, including the corpus callosum and fronto-occipital fasciculus.

    “some studies have shown more focal differences in the thalamus, corpus callosum, cingulum, and superior cerebellar peduncles 136, 137, and some studies also show regions of increased FA in adult females compared with males, including the corpus callosum and fronto-occipital fasciculus137, 138.”

    From Imaging structural and functional brain development in early childhood (2018) · cites this paper as [138]

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.

  • Discussion reverses which sex has the more mature connectivity pattern

    Major

    One discussion passage assigns the more mature SFA pattern to girls and BLA pattern to boys. A later passage assigns those same patterns to boys and girls, respectively.

  • Discussion claims BLA-mPFC coupling that the abstract rules out

    Major

    The discussion says boys show increasing vmPFC-BLA coupling with age, whereas the abstract says neither sex shows increasing mPFC-BLA connectivity.

  • A squared correlation is reported as negative

    Minor

    The reported r2 value is negative, although squaring any correlation cannot produce a negative number. The same problem appears again for the post-scrubbing age-motion correlation, reported as r2 = −0.31.

    Reported -0.22 · recomputed 0.0484

3 of 3

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Related

Authors
Alarcón, G., Cservenka, A., Rudolph, M. D., Fair, D. A., & Nagel, B. J.
Affiliations
Oregon Health & Science University (US)
Corresponding author
Nagel, Bonnie J.
ORCID
Venue
NeuroImage
Publisher
Elsevier BV
Published
2015-07
Volume
115
Pages
235-244
ISSN
1053-8119 (ISSN-L)
DOI
10.1016/j.neuroimage.2015.04.013
PMC
PMC4461484
OpenAlex
W2018473894
Cited by
105
References
86
Citations by year
2026: 6 · 2025: 7 · 2024: 10 · 2023: 4 · 2022: 12 · 2021: 11 · 2020: 9 · 2019: 10 · 2018: 15 · 2017: 10 · 2016: 8 · 2015: 3
FWCI
7.22
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • NeuroImage (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Alcohol Abuse and Alcoholism (R01 AA017664, T32 AA007468-24)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
Keywords
resting-state functional connectivity, basolateral amygdala, superficial amygdala, sex differences, adolescence, brain maturation, medial prefrontal cortex, parieto-occipital cortex, fronto-limbic network, memory processes, sex differences in brain development, anxiety disorders, mood disorders
MeSH terms
Adolescent, Aging, Amygdala, Brain Mapping, Cerebral Cortex, Child, Female, Humans, Image Processing, Computer-Assisted, Intelligence, Magnetic Resonance Imaging, Male, Neural Pathways, Puberty, Reference Values, Rest, Sex Characteristics

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 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

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