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Sex-speci fi c developmental changes in individual edge analysis for male ( A – C ) and for female subjects ( D – F ), where red edges represent signi fi cant decrease, blue edges indicate signi fi cant increases over development, gray edges illustrate the tested edges that all subjects shared in common and the sex-speci fi c changes were emphasized by the thick edges. ( A and C ) Sagittal views of the left hemisphere, ( B and D ) transverse view, and ( C and F ) sagittal views of the right hemisphere, of male and female brains, respectively. ( A ) Two edges showed age-related changes; one in the temporal lobe lost streamlines and the other edge in the occipital lobe gained streamlines. ( C ) An edge in the parietal lobe lost streamlines. ( D ). Two edges in the temporal and the occipital lobes lost streamlines. ( F ) Two edges in the frontal and parietal lobes lost streamlines. 

Sex-speci fi c developmental changes in individual edge analysis for male ( A – C ) and for female subjects ( D – F ), where red edges represent signi fi cant decrease, blue edges indicate signi fi cant increases over development, gray edges illustrate the tested edges that all subjects shared in common and the sex-speci fi c changes were emphasized by the thick edges. ( A and C ) Sagittal views of the left hemisphere, ( B and D ) transverse view, and ( C and F ) sagittal views of the right hemisphere, of male and female brains, respectively. ( A ) Two edges showed age-related changes; one in the temporal lobe lost streamlines and the other edge in the occipital lobe gained streamlines. ( C ) An edge in the parietal lobe lost streamlines. ( D ). Two edges in the temporal and the occipital lobes lost streamlines. ( F ) Two edges in the frontal and parietal lobes lost streamlines. 

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Human brain maturation is characterized by the prolonged development of structural and functional properties of large-scale networks that extends into adulthood. However, it is not clearly understood which features change and which remain stable over time. Here, we examined structural connectivity based on diffusion tensor imaging (DTI) in 121 part...

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... topological features during development. These potentially spared fiber tract types are likely to include long-distance con- nections but also fiber tracts composed of fewer streamlines and intermodule fiber tracts. Fiber tracts of the latter 2 types are often, but not necessarily, also long-distance connections (Supplementary Material S5 and Fig. S4). Therefore, we ana- lyzed all 3 types of fiber tracts in relation to topological ...
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... the spatial (b) and topological (c) properties often overlap but do not always coincide (Supplementary Material S5 and Fig. S4), we investi- gated all 3 cases (da Fontoura Costa et al. 2007;Meunier et al. 2010). In general, short-length and intramodule edges are more numerous than others. Therefore, larger changes in those edges would occur for random selection. Accordingly, we used χ 2 tests to verify any preferential detach- ment that goes beyond the ...
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... global modular organization (see Modularity and Module Member- ship Assignment) did not show sex differences, 3 regions of 20 showed sex-specific developmental changes in within-module strength and participation coefficients (Table 1). In the individ- ual fiber tract analysis, changes that only affected one gender occurred in 7 fiber tracts (11%) (Figs 4-6B, Table 2). There were 4 edges with age effect only in females, and 3 edges only in males, mostly involving occipital and parietal regions. ...
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... but might have been overshadowed by axonal changes and vice versa. Greater amounts of myelination would generate higher FA values ( Mädler et al. 2008;Faria et al. 2010), leading to an increase in Fig. 2A): a longer lasting and higher peaked increase and a delayed decrease in males. (D) For individual edges: we observed sex-specific development (Fig. 4C), which can be explained by 3 representative cases: if the 2 curves strongly overlap they show similar decreasing patterns (case 1), if one of the curves peaks later, one curve shows a decreasing pattern while the other curve is still increasing (case 3) or simply not decreasing yet (case 2). Therefore, depending on the time scale of ...
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... 7. ( A and B ) The schematic summary of the preferential reduction of thick, short, and within-module streamlines over age. ( A ) Location of change: 2 ellipses represent left and right hemispheres and small circles inside hemispheres indicate ROIs. Lines connecting ROIs illustrate fi ber tracts between ROIs. Red lines are where the reduction of streamlines occurred; thick, short or intramodule edges were mostly affected. ( B ) Magnitude of change: Short, thick, or intramodule edges lost more streamlines than long, thin, or intermodule edges. x -axis: either long, thin, or intermodule streamline count (SC), y -axis: either short, thick, or intramodule SC. ( C and D ) Hypothetical developmental curves for males (blue) and females (red). ( C ) For the total streamline count based on the observation of our data (Fig. 2 A ): a longer lasting and higher peaked increase and a delayed decrease in males. ( D ) For individual edges: we observed sex-speci fi c development (Fig. 4 C ), which can be explained by 3 representative cases: if the 2 curves strongly overlap they show similar decreasing patterns (case 1), if one of the curves peaks later, one curve shows a decreasing pattern while the other curve is still increasing (case 3) or simply not decreasing yet (case 2). Therefore, depending on the time scale of the developmental trajectory, males and females may show different patterns.  ...

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... At the network level, a lower variability of some of these networks' topological characteristics and a more consistent topological robustness and stability were estimated in girls. Multiple studies have reporter developmental differences in white matter and maturation of brain circuits between girls and boys (Koolschijn & Crone, 2013 Q20 ; Lenroot & Giedd, 2010;Lim et al., 2015) and sex-related differences in the topological organization of distinct circuits (Ingalhalikar et al., 2014). Our results are not only aligned with these findings but also indicate that there may be inherent sex differences in brain dynamics that are independent of pubertal stage. ...
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Intrinsic brain dynamics play a fundamental role in cognitive function, but their development is incompletely understood. We investigated pubertal changes in temporal fluctuations of intrinsic network topologies (focusing on the strongest connections and coordination patterns) and signals, in an early longitudinal sample from the Adolescent Brain Cognitive Development (ABCD) study, with resting-state fMRI (n = 4,099 at baseline; n = 3,376 at follow-up [median age = 10.0 (1.1) and 12.0 (1.1) years; n = 2,116 with both assessments]). Reproducible, inverse associations between low-frequency signal and topological fluctuations were estimated (p < 0.05, β = −0.20 to −0.02, 95% confidence interval (CI) = [−0.23, −0.001]). Signal (but not topological) fluctuations increased in somatomotor and prefrontal areas with pubertal stage (p < 0.03, β = 0.06–0.07, 95% CI = [0.03, 0.11]), but decreased in orbitofrontal, insular, and cingulate cortices, as well as cerebellum, hippocampus, amygdala, and thalamus (p < 0.05, β = −0.09 to −0.03, 95% CI = [−0.15, −0.001]). Higher temporal signal and topological variability in spatially distributed regions were estimated in girls. In racial/ethnic minorities, several associations between signal and topological fluctuations were in the opposite direction of those in the entire sample, suggesting potential racial differences. Our findings indicate that during puberty, intrinsic signal dynamics change significantly in developed and developing brain regions, but their strongest coordination patterns may already be sufficiently developed and remain temporally consistent.
... Besides age or pubertal development, sex explains some differences in reversal learning performance in our study, with female participants performing better than male. There may be a genuine difference between female and male RL, or the higher performance of girls and women may point to the fact that females mature earlier than males in some regards, e.g., in grey matter development 49 or structural connectivity 50 , and show earlier changes of reward-related behaviours 51 . This would further support the cross-sectional developmental differences observed in our study. ...
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Learning behavioural responses and adapting them based on feedback is crucial from a young age, continuing to develop into young adulthood. This study examines the development trajectory and contributing factors from childhood to adulthood using a reversal learning paradigm. We tested 202 participants aged 10 to 22 in an online study, where they learned and reversed stimulus-outcome associations in a new blocked design paradigm and were assessed for working memory capacity. Results showed that reversal learning performance improved with age, particularly for 10- to 14-year-olds. Flexible responses to negative feedback correlated with better reversal learning. Additionally, pubertal development and working memory were positively associated with reversal learning. These findings align with previous research, highlighting flexible feedback responses as a key factor in reversal learning. As the overall rate of flexible reactions did not change with age, it could support reversal learning independent of age, potentially changing its role during development.
... At the same time, throughout adolescence, the brain regions related to inhibitory functions gradually mature and become more activated [32]. Since adolescent girls' brains mature earlier than boys' [33], this leads to different trends in the changes in depression network intensity between adolescent boys and girls. Furthermore, "sad mood" is a core symptom in the depression networks of all three grade groups. ...
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Background: Adolescence is a high-risk period for depression, especially after the COVID-19 pandemic, when adolescent depression has become increasingly severe. This study employs network analysis to identify core symptoms at various stages. It explores the differences in depression symptom characteristics among Chinese adolescents of different genders during elementary, middle, and high school periods. Methods: A convenience sampling method was used to select 1553 students from various elementary, middle, and high schools in a specific city as participants. Their depression symptoms were assessed using the The Patient Health Questionnaire-9 (PHQ-9) depression screening scale. Using graph theory-based network analysis, this study constructs a depression symptom model via a correlation network and evaluates symptom nodes and their interconnections. Results: The study found significant differences in the detection rates of depression symptoms among the three grade levels (p <0.001). However, no significant differences were found between male and female students in the detection rates and PHQ-9 scores (p >0.05). Through network analysis, this study identified the network changes in depression symptoms among Chinese adolescents of different grades and genders. The results show that “depressed mood” is the core symptom in the elementary and high school groups. At the same time, “fatigue” is the central factor affecting the depression network in the middle school group. Negative emotions and fatigue are the primary symptoms that run through the entire adolescent depression network. Conclusions: This study reveals the heterogeneity of depression symptom networks among adolescent groups of different genders and grades, providing a theoretical basis for personalized interventions for adolescent depression in the future.
... Aging is a complex biological process that is associated with degradation of white matter tracts (a reduction in myelin density, axonal degeneration, and decline in tract numbers) (Peters 2006;Betzel et al. 2014;Lim et al. 2015;Coelho et al. 2021), gray matter volume (Sullivan and Pfefferbaum 2006), alteration in neurotransmitter levels (Roalf et al. 2020), and changes in large scale brain networks' coordination leading to cognitive and behavioral impairments (Li et al. 2020b). It is well known that the impact of aging on brain function is nonlinear and diverse, vary person to person, leading to the deterioration of some functions (Grady et al. 2010), while few other functions, such as inductive reasoning, verbal f luency, and executive attention, may even improve with age (Salthouse 2012;Veŕıssimo et al. 2022). ...
... Age-associated loss of the brain's anatomical connectivity has been of intense interest in many recent studies (Betzel et al. 2014;Lim et al. 2015;Perry et al. 2015). Nevertheless, many of these studies have overlooked the impact on the SR and LR TLs, exceptions, and their spatial distribution with age, which we quantified here and has been one of the key contributions of this work. ...
Article
Optimal brain function is shaped by a combination of global information integration, facilitated by long-range connections, and local processing, which relies on short-range connections and underlying biological factors. With aging, anatomical connectivity undergoes significant deterioration, which affects the brain’s overall function. Despite the structural loss, previous research has shown that normative patterns of functions remain intact across the lifespan, defined as the compensatory mechanism of the aging brain. However, the crucial components in guiding the compensatory preservation of the dynamical complexity and the underlying mechanisms remain uncovered. Moreover, it remains largely unknown how the brain readjusts its biological parameters to maintain optimal brain dynamics with age; in this work, we provide a parsimonious mechanism using a whole-brain generative model to uncover the role of sub-communities comprised of short-range and long-range connectivity in driving the dynamic compensation process in the aging brain. We utilize two neuroimaging datasets to demonstrate how short- and long-range white matter tracts affect compensatory mechanisms. We unveil their modulation of intrinsic global scaling parameters, such as global coupling strength and conduction delay, via a personalized large-scale brain model. Our key finding suggests that short-range tracts predominantly amplify global coupling strength with age, potentially representing an epiphenomenon of the compensatory mechanism. This mechanistically explains the significance of short-range connections in compensating for the major loss of long-range connections during aging. This insight could help identify alternative avenues to address aging-related diseases where long-range connections are significantly deteriorated.
... However, this decrease does not correspond to a loss of anatomical connections because we find that neither average degree, average tract length, nor average tract density monotonically decrease with age when analyzing diffusion MRI scans using the Q-Ball method (Supporting Information Figure S16). This seems to contradict previous findings, which report decreases (Betzel et al., 2014;Lim, Han, Uhlhaas, & Kaiser, 2015). However, previous results employed the more simple diffusion tension imaging (DTI) method, which is known to be less accurate at performing tractography (Garyfallidis et al., 2014;Jones, Knösche, & Turner, 2013;Rokem et al., 2015). ...
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The integration-segregation framework is a popular first step to understand brain dynamics because it simplifies brain dynamics into two states based on global versus local signaling patterns. However, there is no consensus for how to best define the two states. Here, we map integration and segregation to order and disorder states from the Ising model in physics to calculate state probabilities, Pint and Pseg, from functional MRI data. We find that integration decreases and segregation increases with age across three databases. Changes are consistent with weakened connection strength among regions rather than topological connectivity based on structural and diffusion MRI data.
... Furthermore, disorders of white matter integrity in the angular and supramarginal gyrus were adjusted during treatment. FA value can measure the integrity of white matter microstructure, reflecting potential changes in axon diameter, density, and myelination (Lim et al., 2015). The DLPFC plays an important role in cognitive The FA values from ROIs of the patient (t0, t1, t2 and t3). ...
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Purpose Long-term post-stroke cognitive impairment (PSCI) exhibits an accelerated rate of long-term cognitive decline, which can impair communication, limit social engagement, and increase rate of institutional dependence. The aim of this case report is to provide evidence for the potential of home-based transcutaneous auricular vagus nerve stimulation (taVNS) for home-bound patients with severe, long-term PSCI. Methods A 71-year-old male suffered a stroke two and a half years ago, which imaging reported foci of cerebral infarction visible in the left temporal and parietal lobes. The patient was performed taVNS twice a day for 30 min, 5 times a week for 8 weeks. The patient was evaluated the changes of cognitive function and brain white matter at 4 time points: baseline (t0), 4 weeks without taVNS after baseline (t1), 4 weeks of intervention (t2), and 8 weeks of intervention (t3). The effect of taVNS on white matter changes was visualized by DTI. Results After 8 weeks of taVNS treatment, the scores of Montreal cognitive assessment improved and the time to complete the shape trails test decreased. The DTI results showed that white matter in bilateral dorsal lateral prefrontal cortex remodeled after taVNS. Conclusion Eight-week home-based taVNS may be beneficial to long-term PSCI. Further studies of home-based taVNS treating patients with long-term PSCI are needed.
... Between ages 7 and 11, female subcortical forebrain nuclei reach adult volume, while males' volume is greater but likely reduces later in adulthood [24]. Nerve fiber tract streamline reduction occurs earlier in females [25], while occipital area thinning is faster in males [26]. Many species are characterized by different maturation rates between sexes [27][28][29][30][31]. Direct temporal comparison of females and males is challenged by sex-specific phenotypic timelines, evident in quantifiable gene expression patterns. ...
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Many species, including fruit flies (Drosophila melanogaster), are sexually dimorphic. Phenotypic variation in morphology, physiology, and behavior can affect development, reproduction, health, and aging. Therefore, designating sex as a variable and sex-blocking should be considered when designing experiments. The brain regulates phenotypes throughout the lifespan by balancing survival and reproduction, and sex-specific development at each life stage is likely. Changes in morphology and physiology are governed by differential gene expression, a quantifiable molecular marker for age- and sex-specific variations. We assessed the fruit fly brain transcriptome at three adult ages for gene expression signatures of sex, age, and sex-by-age: 6698 genes were differentially expressed between sexes, with the most divergence at 3 days. Between ages, 31.1% of 6084 differentially expressed genes (1890 genes) share similar expression patterns from 3 to 7 days in females, and from 7 to 14 days in males. Most of these genes (90.5%, 1712) were upregulated and enriched for chemical stimulus detection and/or cilium regulation. Our data highlight an important delay in male brain gene regulation compared to females. Because significant delays in expression could confound comparisons between sexes, studies of sexual dimorphism at phenotypically comparable life stages rather than chronological age should be more biologically relevant.
... Given that there are sex-and age-related differences in psychological functioning during adolescence, particularly in depression (Nolen-Hoeksema and Girgus, 1994;Frey et al., 2020;Hosozawa et al., 2024), and as with most research in this area, we used sex and age as covariates in our analyses. Physical development during adolescence is also reflective of sex and age; this appears to include brain development and connectivity, as evidence emerges in this area (Dennis et al., 2013;Ingalhalikar et al., 2014;Lim et al., 2015;Kaczkurkin et al., 2019). Research examining structural connectivity in adolescents often accounts for both sex and age, so we followed this convention in our subsequent analyses. ...
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Introduction This study evaluated changes in the white matter of the brain and psychological health variables, resulting from a neuroscience-based mindfulness intervention, the Training for Awareness, Resilience, and Action (TARA), in a population of healthy adolescents. Methods A total of 100 healthy adolescents (57 female, age ranges 14–18 years) were randomized into the 12-week TARA intervention or a waitlist-control group. All participants were imaged with diffusion MRI to quantify white matter connectivity between brain regions. Imaging occurred at baseline/randomization and after 12 weeks of baseline (pre- and post-intervention in the TARA group). We hypothesized that structural connectivity in the striatum and interoceptive networks would increase following the TARA intervention, and that, this increased connectivity would relate to psychological health metrics from the Strengths and Difficulties Questionnaire (SDQ) and the Insomnia Severity Index (ISI). The TARA intervention and all assessments, except for the MRIs, were fully remotely delivered using secure telehealth platforms and online electronic data capture systems. Results The TARA intervention showed high consistency, tolerability, safety, recruitment, fidelity, adherence, and retention. After 12 weeks, the TARA group, but not controls, also demonstrated significantly improved sleep quality (p = 0.02), and changes in the right putamen node strength were related to this improved sleep quality (r = −0.42, p = 0.006). Similarly, the TARA group, but not controls, had significantly increased right insula node strength related to improved emotional well-being (r = −0.31, p = 0.04). Finally, we used the network-based statistics to identify a white matter interoception network that strengthened following TARA (p = 0.009). Discussion These results suggest that the TARA mindfulness-based intervention in healthy adolescents is feasible and safe, and it may act to increase structural connectivity strength in interoceptive brain regions. Furthermore, these white matter changes are associated with improved adolescent sleep quality and emotional well-being. Our results suggest that TARA could be a promising fully remotely delivered intervention for improving psychological well-being in adolescents. As our findings suggest that TARA affects brain regions in healthy adolescents, which are also known to be altered during depression in adolescents, future studies will examine the effects of TARA on depressed adolescents. Clinical trial registration https://clinicaltrials.gov/study/NCT04254796.
... 28 This was attributed to the anatomical differences between male and female sex 7 and the fact that boys develop later than girls. 29 The fact that both sexes were equal in daytime urinary incontinence in the present study may be related to the small sample. ...
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Background and Aim Urinary incontinence is an important problem with potentially adverse effects on the psychological, social and personality development of children. Today, with the developing technology, the use of information and communication technologies such as wearable technology, message services and mobile applications has become widespread in solving health problems. In this study, it was aimed to develop a mobile application that facilitates the follow‐up of children, increases their compliance with treatment and ensures the continuity of communication between them and the health worker. The methodology, design and preliminary evaluation results of the mobile application are presented in this article. Methods During the development process of the mobile application, the content was first created in line with the literature review. After the content was determined, the interface design was made on MS Word and Photoshop software. At this stage, six experts were consulted for content and design. The mobile application, finalised in design, was implemented on Android and IOS platforms. After the mobile application was created, 10 children and their families were interviewed. Results Nine of the families (90%) found the developed mobile application useful and easy to use. Families' suggestions to improve the mobile application were to make it more interesting for children and to enrich its content. Conclusion In line with the feedback, the mobile application was updated and finalised. Preliminary results are promising that the developed mobile application can be used as an aid to treatment in children with urinary incontinence. With the mobile application developed, urotherapy training was not limited to the time they visited the hospital. This suggests that the mobile application can eliminate the problem of partial or omitted treatment. This research has shown that leveraging technology can be a good option to increase treatment success. Clinical Trial Number NCT05815940
... Overall, our findings align with most prior research that suggests little to no meaningful differences on girls and boys cognitive, language, and motor performance, particularly when examined at the latent level. Yet, the direction of the differences is broadly supportive of neurological findings showing that girls mature more rapidly than boys (Lim et al., 2015) and girls typically earn higher mean scores on measures of cognitive, language, and motor abilities at very young ages (Kaufman & Kaufman, 2004). ...
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This study tested the assumption that the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4) functions similarly for boys and girls and for four age groups. The Bayley-4 American norming sample of 1,700 children ages 0–42 months (3.5 years) was used, which included 50% boys and girls. Fifty-three percent of the children identified as White, 22.1% as Hispanic, 12.5% as Black, 8.5% as other, and 4.0% as Asian. A confirmatory factor analysis demonstrated the three-factor structure of cognitive, language, and motor abilities fit the data well (comparative fit index = .99, root-mean-square of error of approximation = .08, standardized root-mean-square residual = .02) and fit significantly better than the two- and one-factor models. The correlations between the latent factors were moderate (r = .73) to large sized (r = .81). Measurement and structural invariance were tested for boys and girls and four age groups (0–5, 6–13, 14–25, and 26–42 months). Residual invariance was supported for girls and boys, and intercept invariance was supported for the four age groups. The measurement invariance results suggest the Bayley-4 is not biased toward these gender and age groups, and group comparisons and decision making can be made with the Bayley-4 scores. Structural invariance findings suggested some differences for gender and age groups. The relations between the cognitive, language, and motor factors and factor variances were equal across girls and boys but differed significantly across the four age groups. Girls scored significantly higher on the three latent means, but these differences were small to negligible.