This study investigated whether childhood white matter organization in those with and without ADHD predicted the emergence of internalizing problems in adolescence. Further, we aimed to determine whether (i) this longitudinal effect was mediated by motor skill level, and/or (ii) white matter organization in children with ADHD mediated the expected relationship between motor skill level and internalizing problems in adolescence. Participants were 40 children with ADHD and 36 typically developing (TD) controls aged between 8 and 13 years, who were followed-up during adolescence (12-18 years). All underwent diffusion MRI at Time 1, and assessment of motor competence using the Movement ABC-2 (MABC-2). At Time 2, internalizing problems (i.e., 'depression', 'anxiety', and 'somatization') were measured using the parent- and self-report Behavior Assessment System for Children (BASC). Following pre-processing of diffusion MRI scans, fixel based analysis was conducted and fibre cross-section (FC) extracted. TractSeg was then used to delineate the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the uncinate fasciculus (UC). Results showed that childhood FC within the UF was a significant predictor of parent and child-rated depression scores in adolescence. Further, childhood FC of the bilaterial ILF was a significant predictor of parent report depression scores in adolescence. These effects were stable for those with and without ADHD, and no group differences in FC were observed in those white matter regions found to be associated with adolescent depressive symptoms. We failed to find evidence that motor ability mediated the relationship between white matter organization of the UF of ILF and depressive symptoms. When childhood motor ability was considered as a predictor of adolescent depressive scores (an effect that was significant for parent reported effects), this effect was mediated by childhood FC of the UF. This work suggests that low motor skill in children with and without ADHD may provide a developmental marker for emotional and behavioral dysregulation in adolescence, with this effect partly explained by childhood white matter organization within fronto-limbic circuitry.

Particulate matter (PM2.5) has been linked with brain and cognitive changes; however, longitudinal evidence characterizing associations with white matter (WM) development across adolescence remains limited. This study examined longitudinal associations between baseline PM2.5 and fronto-limbic WM integrity), as well as separately examined associations with cognition and substance use (SU), across adolescence. Baseline Adolscent Brain Cognitive Development (ABCD) Study (n = 4,511; 47.4% female; mean age = 9.9 years, SD = 0.5, range = 9-11; 57.0% White, 10.5% Black, 20.4% Hispanic, 2.3% Asian, and 9.8% multiracial). Linear mixed effects/logistical regression tested for PM2.5 interactions with age/sex, controlling for neighborhood factors. PM2.5 and fronto-limbic mean diffusivity (MD) and fractional anisotropy (FA) associations were observed, Cohen's d effect sizes were reported. At age 9, increased PM2.5 was associated with increased FA in the anterior thalamic radiation (ATR), fornix, and uncinate fasciculus (UNC), whereas by age 14, PM2.5 was linked with reduced FA in all tracts. In the superior longitudinal fasciculus (SLF), PM2.5 was linked to increased MD at age 9 and reduced FA at ages 12 and 14. We also observed reductions in MD in the fornix at ages 12 and 14, and in the SLF and UNC at age 14. The links between PM2.5 and cognition and SU were not significant. Findings suggest the association between baseline PM2.5 exposure and fronto-limbic WM varies as a function of age at assessment, with positive associations observed at younger ages and negative associations at older ages.

Cognitive models propose that reading aloud relies on two routes, a lexical route for familiar word recognition and a sublexical route for graphene-to-phoneme conversion. Selective disruption of these routes results in surface or phonological dyslexia, respectively. Although the dual route model is well supported behaviorally, its white matter substrates remain incompletely characterized. This study examined the anatomical correlates of acquired lexical and sublexical reading impairments in patients with high-grade glioma in the dominant hemisphere. Thirty-seven patients underwent diffusion tensor imaging (DTI) and a comprehensive reading battery. Reading aloud of regular and irregular words, and pseudowords was used to classify patients as having intact reading, surface dyslexia or phonological dyslexia, based on normative criteria. Six language-related white matter tracts were reconstructed individually for each patient using subject-specific tractography. Each tract was then systematically segmented along its longitudinal axis, allowing diffusion parameters to be extracted from anatomically defined subsegments. Lesion-tract overlap measures were computed to quantify focal tract involvement. Fourteen patients exhibited impaired sublexical reading, 12 impaired lexical reading, and 11 intact reading. Deficits in the sublexical route were more frequent among patients with arcuate fasciculus lesion overlap, and sublexical error rates correlated with global tract integrity. Deficits in the lexical route were associated with the posterior temporal segment of the inferior longitudinal fasciculus, where surface dyslexia errors correlated with reduced fractional anisotropy. In contrast, uncinate fasciculus involvement was more frequent among patients with intact reading, indicating it does not contribute critically to either reading route. These findings provide a fine-grained structure-function mapping of the dual route reading model onto white matter pathways.

Adolescence and young adulthood are critical periods for the emergence of bipolar disorder (BD). Instability in sleep and rest-activity rhythms is associated with elevated risk for BD, yet little is known about the neural correlates of this vulnerability. White matter organization in fronto-limbic pathways, which support mood regulation and show sensitivity to sleep/rest-activity rhythm disruption, offers a promising avenue for investigation. Participants (16-24y;N = 112) recruited across a spectrum of mania vulnerability (MOODS-SRL) completed 14 days of actigraphy followed by a neuroimaging assessment. Diffusion MRI was used to derive Neurite Orientation Dispersion and Density Imaging, focusing on the Orientation Dispersion Index (ODI) of the cingulum bundle, uncinate fasciculus, and forceps minor. Clinician-rated symptoms of mania and depression were assessed at baseline and 6-months follow-up. We evaluated whether the links between actigraphy-derived sleep duration variability, sleep onset variability, and Circadian Function Index (CFI; index of circadian rhythm robustness) and white matter ODI were moderated by baseline mania vulnerability, and tested whether baseline ODI predicted 6-month mood symptoms. At higher levels of mania vulnerability, lower CFI (greater rest-activity instability) associated with higher ODI (greater white matter disorganization) in the cingulum bundle (β=-0.22;P = 0.029) and uncinate fasciculus (β = -0.22;P = 0.020). Moreover, higher uncinate fasciculus ODI predicted greater mania symptoms at 6-month follow-up and fully mediated the CFI-mania symptom association (β = -0.10;95 %CI[-0.14,-0.02]). Rest-activity instability may disrupt fronto-limbic white matter, increasing risk to mania in those at elevated vulnerability for BD. Stabilizing rest-activity rhythms in at-risk individuals may help preserve white matter integrity and mitigate BD risk.

AIM: To determine hemispheric asymmetries in major white matter tracts using diffusion tensor imaging (DTI) metrics and morphometric measurements, as comprehensive multitract analyses remain limited. MATERIAL and METHODS: Diffusion MRI data from 102 healthy adults enrolled in the Human Connectome Project (HCP) were analyzed using DSI Studio to reconstruct 17 major white- matter tracts bilaterally. For each tract, diffusion metrics (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], axial diffusivity [AD], quantitative anisotropy [QA], isotropic value [ISO], restricted diffusion imaging [RDI], and normalized RDI [nrdı]) and morphometric parameters (fiber count, mean length, trunk volume, branch volume, total volume, and termination region areas) were quantified. Paired t-tests compared left-right hemispheric differences. Multiple comparison corrections were performed with the Benjamini-Krieger-Yekutieli procedure, and effect sizes were reported as Cohen's d. RESULTS: Significant hemispheric asymmetries were observed in most tracts. FA was significantly higher in the left hemisphere (p<0.001) for the arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), and uncinate fasciculus (UF). Mean diffusivity (MD) demonstrated left dominance in the UF and SLF2-3 (p=0.009). QA was predominantly left- lateralized across multiple tracts, including AF, IFOF, ILF, and frontal aslant tract (FAT) (p<0.01, Cohen's d: 0.42 to 1.17), except for the vertical occipital fasciculus (VOF), where rightward dominance was noted (Cohen's d: -0.55). Tract-trunk-branch volumes were predominantly left-lateralized in frontal lobe pathways such as AF, SLF1, SLF2, FAT, and UF (p<0.01). Rightward dominance was observed in SLF3, parietal aslant tract (PAT), IFOF, ILF, and middle longitudinal fasciculus (MLF) (p<0.05). Similar asymmetries were observed in termination region areas, fiber counts, and fiber lengths (p<0.001). CONCLUSION: Widespread hemispheric asymmetries were observed across multiple pathways. Such asymmetry may reflect distinct hemispheric functional specialization and the neurological basis of lateralized functions.

Reading is supported by neural systems that change across the lifespan, yet the development of reading-related white matter remains underexplored, particularly in non-alphabetic writing systems. This cross-sectional study examined white matter-reading associations in 126 Mandarin Chinese readers aged 7 to 77 years. Diffusion tensor imaging quantified fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in seven pairs of bilateral reading-related tracts: the arcuate fasciculus (AF), superior longitudinal fasciculus (SLF I, II, and III), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), and uncinate fasciculus (UF). Most tracts showed nonlinear age-related trajectories, with FA generally following an inverted U-shaped pattern and MD, AD, and RD showing opposite U-shaped patterns; by contrast, FA in the left ILF and right UF increased linearly with age. In addition, word reading efficiency was positively associated with FA in the bilateral AF, bilateral SLF III, and right SLF II. These FA effects were accompanied by lower RD across all significant tracts and lower MD in the right-hemisphere tracts. Sentence reading fluency showed a more limited association with FA, mainly involving the right AF. Further, age moderated the association between word reading efficiency and FA in the right AF and right SLF II: better word reading fluency predicted higher FA at younger ages, whereas the association became weak in adulthood and negative at older ages. These findings reveal heterogeneous maturation of reading-related white matter pathways and highlight both stable and age-dependent structural correlates of reading fluency across the lifespan in Chinese readers.