Asymmetric information flow in brain networks supporting expressive language in childhood.

Low-beta (13-23 Hz) event-related desynchrony (ERD), a neural signature of expressive language, lateralizes from bilateral to left hemisphere in development. In contrast, low-beta event-related synchrony (ERS), thought to reflect inhibition, lateralizes from bilateral to the right hemisphere across development. Using whole-brain directed connectivity analyses, we aimed to characterize hemispheric and regional contributions to expressive language, in childhood. We studied 80 children and adolescents, 4 to less than 19 years of age, performing covert auditory verb generation in magnetoencephalography. Outdegree, indegree, and betweenness centrality were used to differentiate regions acting as drivers, receivers, and bridging hubs, respectively. The number of suprathreshold connections significantly increased with age for delta band (p < .01). Delta outflow was mapped to left inferior frontal gyrus (IFG), while regions of right hemisphere, including right IFG, showed significant inflow. The right parietal cortex showed significant ERS, but without corresponding outdegree or indegree. Betweenness mapped to midline cortical and subcortical structures. Results suggest Broca's area develops a driving role in the language network, while Broca's homologue receives information without necessarily propagating it. Subcortical and midline hubs act as intrahemispheric relays. Findings suggest that Broca's homologue is inhibited during expressive language, in development.

Effect of continuous cooling on inhibition and attention while wearing firefighter's PPE in a hot environment.

Firefighting is physically and mentally strenuous, requiring rapid, appropriate decision-making in hot environments. Intact cognitive function is imperative to firefighters' effectiveness and safety. The study purpose was to investigate the effect of hyperthermia and the effect of body cooling on sustained attention and response inhibition while wearing firefighters' personal protective ensembles after exercise in a hot environment. Twelve healthy males were recruited to participate in two randomly assigned exercise sessions (walking on a treadmill for 40 min at 40% [Formula: see text] O2max while wearing firefighter's protective ensemble) in a hot environment: control (no cooling) and intervention (cooling). For intervention sessions, a cooling garment was worn underneath firefighter's protective ensemble and infused with 18 °C water supplied by an external water circulator. Participants performed a computerized Go/No-Go (a measure of cognitive function) test three times at baseline and post-exercise for each experimental session. Participants completed baseline testing while wearing cotton athletic clothing. The exercise continued until the core temperature reached ∼39 °C (for all subjects regardless of cooling or non-cooling experimental sessions). Following hyperthermia, participants' physiological responses were significantly increased after exercise. Subjects' reaction time was significantly reduced (improved) after experiencing thermal strain and reaching hyperthermia. The cooling method had a significant impact on suppressing the physiological load, i.e., body cooling delayed the time to reach a Tc of 39 °C (p ≤ 0.05), but not cognitive inhibition and attention (reaction time and accuracy). Unexpectedly, hyperthermia resulted in shorter reaction time following exercise (16.64 ± 5.62; p < 0.03), likely influenced by increased attention/vigilance. Hyperthermia may trigger an acute increase in alertness, causing decreased reaction time.

Detrended connectometry analysis to assess white matter correlates of performance in childhood.

The white matter of the brain develops in a robust, regionally-variant, nonlinear manner during childhood. To relate white matter connectivity to performance, these regional nonlinear effects of age must be accounted for. Here, we identify white matter correlates of gross intellectual functioning using cutting-edge diffusion analyses inside a data-driven two-step regression framework. A total of 98 participants, ages 3-18 years, were included in the analyses. First, white matter connectivity was modeled as a function of age for each fiber direction at each voxel, extracted from the spin distribution function, using a 6th-order B-spline. The smoothing parameter for each direction was chosen by minimizing generalized cross-validation (GCV), which prevents overfitting while remaining sensitive to potentially nonlinear effects of age. In the second step, the resulting Gaussian residuals were modeled as a function of either full-scale IQ (FSIQ), or of verbal IQ (VIQ) and performance IQ (PIQ), using a linear regression framework (connectometry). Graph theoretical analyses were also performed to assess how each predictor relates to global topological changes, including average clustering coefficient, characteristic path length, global efficiency, average local efficiency, and small worldness. Analyses revealed widespread positive associations between white matter connectivity and FSIQ, including regions of the corpus callosum, fornix, and corticothalamic tracts (FDRq < .05). A separate regression model revealed a selective positive relationship between VIQ and white matter connectivity in predominately frontal tracts (e.g., anterior corticothalamic radiations, fornix, anterior corpus callosum, frontopontine tracts); in contrast, PIQ predicted white matter connectivity in the posterior brain (e.g. parietopontine tracts, posterior corticothalamic radiations, posterior corticostriatal projections), (FDRq < .05). No negative correlations were observed. Graph analyses revealed FSIQ, VIQ while controlling for PIQ, and PIQ while controlling for VIQ increase clustering coefficient, global efficiency, local efficiency, and small worldness, and decrease characteristic path length of the network. Results indicate regional white matter changes related to cognitive skills in childhood, independent of age.

fMRI connectivity of expressive language in young children and adolescents.

Studies of language representation in development have shown a bilateral distributed pattern of activation that becomes increasingly left-lateralized and focal from young childhood to adulthood. However, the level by which canonical and extra-canonical regions, including subcortical and cerebellar regions, contribute to language during development has not been well-characterized. In this study, we employed fMRI connectivity analyses (fcMRI) to characterize the distributed network supporting expressive language in a group of young children (age 4-6) and adolescents (age 16-18). We conducted an fcMRI analysis using seed-to-voxel and seed-to-ROI (region of interest) strategies to investigate interactions of left pars triangularis with other brain areas. The analyses showed significant interhemispheric connectivity in young children, with a minimal connectivity of the left pars triangularis to subcortical and cerebellar regions. In contrast, adolescents showed significant connectivity between the left IFG seed and left perisylvian cortex, left caudate and putamen, and regions of the right cerebellum. Importantly, fcMRI analyses indicated significant differences between groups at 3 anatomical clusters, including left IFG, left supramarginal gyrus, and right cerebellar crura, suggesting a role in the functional development of language.

Ictal connectivity in childhood absence epilepsy: Associations with outcome.

OBJECTIVE: The understanding of childhood absence epilepsy (CAE) has been revolutionized over the past decade, but the biological mechanisms responsible for variable treatment outcomes are unknown. Our purpose in this prospective observational study was to determine how pretreatment ictal network pathways, defined using a combined electroencephalography (EEG)-functional magnetic resonance imaging (EEG-fMRI) and magnetoencephalography (MEG) effective connectivity analysis, were related to treatment response. METHODS: Sixteen children with newly diagnosed and drug-naive CAE had 31 typical absence seizures during EEG-fMRI and 74 during MEG. The spatial extent of the pretreatment ictal network was defined using fMRI hemodynamic response with an event-related independent component analysis (eICA). This spatially defined pretreatment ictal network supplied prior information for MEG-effective connectivity analysis calculated using phase slope index (PSI). Treatment outcome was assessed 2 years following diagnosis and dichotomized to ethosuximide (ETX)-treatment responders (N = 11) or nonresponders (N = 5). Effective connectivity of the pretreatment ictal network was compared to the treatment response. RESULTS: Patterns of pretreatment connectivity demonstrated strongest connections in the thalamus and posterior brain regions (parietal, posterior cingulate, angular gyrus, precuneus, and occipital) at delta frequencies and the frontal cortices at gamma frequencies (P < .05). ETX treatment nonresponders had pretreatment connectivity, which was decreased in the precuneus region and increased in the frontal cortex compared to ETX responders (P < .05). SIGNIFICANCE: Pretreatment ictal connectivity differences in children with CAE were associated with response to antiepileptic treatment. This is a possible mechanism for the variable treatment response seen in patients sharing the same epilepsy syndrome.

Extremely preterm children exhibit increased interhemispheric connectivity for language: findings from fMRI-constrained MEG analysis.

Children born extremely preterm are at significant risk for cognitive impairment, including language deficits. The relationship between preterm birth and neurological changes that underlie cognitive deficits is poorly understood. We use a stories-listening task in fMRI and MEG to characterize language network representation and connectivity in children born extremely preterm (n = 15, <28 weeks gestation, ages 4-6 years), and in a group of typically developing control participants (n = 15, term birth, 4-6 years). Participants completed a brief neuropsychological assessment. Conventional fMRI analyses revealed no significant differences in language network representation across groups (p > .05, corrected). The whole-group fMRI activation map was parcellated to define the language network as a set of discrete nodes, and the timecourse of neuronal activity at each position was estimated using linearly constrained minimum variance beamformer in MEG. Virtual timecourses were subjected to connectivity and network-based analyses. We observed significantly increased beta-band functional connectivity in extremely preterm compared to controls (p < .05). Specifically, we observed an increase in connectivity between left and right perisylvian cortex. Subsequent effective connectivity analyses revealed that hyperconnectivity in preterms was due to significantly increased information flux originating from the right hemisphere (p < 0.05). The total strength and density of the language network were not related to language or nonverbal performance, suggesting that the observed hyperconnectivity is a "pure" effect of prematurity. Although our extremely preterm children exhibited typical language network architecture, we observed significantly altered network dynamics, indicating reliance on an alternative neural strategy for the language task.

Cortical morphology, epileptiform discharges, and neuropsychological performance in BECTS.

OBJECTIVES: The aim of this study was to understand the relationship between cortical morphology, centrotemporal spike (CTS), and neuropsychological functioning in children with BECTS compared to their typically developing peers. MATERIALS AND METHODS: To examine whole-brain differences in cortical thickness between groups, a general linear model approach was applied to T1-weighted structural magnetic resonance imaging (MRI) in children with BECTS and typically developing children. Further region-of-interest (ROI) analyses were performed to examine the effects of frequency and lateralization of CTS. In addition, the relationship between Processing Speed Index (PSI) and cortical thickness was investigated. RESULTS: Twenty-three patients with BECTS and thirty-two controls were included. There was no statistically significant difference in global cortical thickness between groups. With ROI analyses, we found significantly thinner cortex within right pars opercularis when comparing children with right predominant CTS, and with very frequent right CTS (>10/min) to the control group (P = 0.028 and P = 0.026, respectively). A statistically significant interaction of group (controls vs BECTS) and PSI was seen in bilateral frontal and right superior parietal cortices, indicating a positive relationship between cortical thickness and PSI in healthy controls but not BECTS. CONCLUSION: A region of cortex where right CTS may originate was thinner in BECTS compared to children without BECTS. Typically developing children with faster processing speed had thicker cortices in regions supporting visuomotor integration, motor, and executive function, but this relationship was not observed in BECTS. These results suggest that BECTS is associated with atypical cortical morphology that may underlie poorer neuropsychological performance.

Obese adolescents with type 2 diabetes perform worse than controls on cognitive and behavioral assessments.

BACKGROUND: Children with type 1 diabetes demonstrate worse cognitive performance compared with their peers. Little is known regarding the cognitive and behavioral performance in obese adolescents with type 2 diabetes. METHODS: Cross sectional evaluation of 20 obese adolescents with type 2 diabetes and 20 healthy adolescents was performed in Cincinnati, Ohio. Cognitive tests that included measures of processing speed, working memory, verbal and semantic fluency and parent reports of executive function and problem behavior were compared. Academic achievement and the relationship between cognitive/behavioral scores and diabetes duration and diabetes control (hemoglobin A1c) were assessed in the type 2 diabetes group only. RESULTS: The type 2 diabetes group had mean duration of diabetes of 2.8 ± 2.2 yr and hemoglobin A1c of 7.9 ± 2.2%. Adolescents with type 2 diabetes scored lower than controls on tests of working and verbal memory and processing speed (all p < 0.05) and worse for Internalizing, Externalizing, and Total Problems behaviors on the Child Behavior Checklist (all p < 0.05). Adolescents with type 2 diabetes scored below the population mean in academic achievement, most notably calculation. Working memory and processing speed were negatively correlated with duration of diabetes (r = -0.50 and -0.47, respectively, p < 0.05). CONCLUSIONS: Obese youth with type 2 diabetes score poorly compared with controls on multiple assessments of cognitive function and adaptive behavior. Further work is needed to determine if these effects are driven by obesity, diabetes or other demographic and socioeconomic risk factors.

Changes of White Matter Diffusion Anisotropy in Response to a 6-Week iPad Application-Based Occupational Therapy Intervention in Children with Surgically Treated Hydrocephalus: A Pilot Study.

Objective Our aims were (1) to test whether diffusion tensor imaging (DTI) could detect underlying white matter (WM) changes after a 6-week iPad application-based occupational therapy (OT) intervention in children with surgically treated hydrocephalus (HCP); and (2) to explore the association between WM changes and performance outcomes. Methods Five children (age range: 6.05-9.10 years) with surgically treated HCP completed an intensive iPad-based OT intervention targeting common domains of long-term deficits in children with HCP. The intervention included 6 weekly sessions in an OT clinic supplementing home-based program (1 hour/day, 4 days/week). DTI and neuropsychological assessments were performed before and after the intervention. Observation After the therapy, significant increases in fractional anisotropy (FA) and/or decreases in radial diffusivity were found in extensive WM areas. All participants demonstrated an increased perceptual reasoning index (PRI, Wechsler Abbreviated Scale of Intelligence: 2nd edition, PRI gains = 14.20 ± 7.56, p = 0.014). A significant positive correlation was found between PRI increase and the increase of FA in the right posterior limb of the internal capsule and the right external capsule (both p < 0.05). Conclusion This study provides initial evidence of DTI's sensitivity to detect subtle WM changes associated with performance improvements in response to a 6-week OT intervention in children with HCP.

Cortical thickness in children receiving intensive therapy for idiopathic apraxia of speech.

Children with idiopathic apraxia experience difficulties planning the movements necessary for intelligible speech. There is increasing evidence that targeted early interventions, such as Prompts for Restructuring Oral Muscular Phonetic Targets (PROMPT), can be effective in treating these disorders. In this study, we investigate possible cortical thickness correlates of idiopathic apraxia of speech in childhood, and changes associated with participation in an 8-week block of PROMPT therapy. We found that children with idiopathic apraxia (n = 11), aged 3-6 years, had significantly thicker left supramarginal gyri than a group of typically-developing age-matched controls (n = 11), t(20) = 2.84, p ≤ 0.05. Over the course of therapy, the children with apraxia (n = 9) experienced significant thinning of the left posterior superior temporal gyrus (canonical Wernicke's area), t(8) = 2.42, p ≤ 0.05. This is the first study to demonstrate experience-dependent structural plasticity in children receiving therapy for speech sound disorders.

Changes in voice onset time and motor speech skills in children following motor speech therapy: Evidence from /pa/ productions.

This study evaluated changes in motor speech control and inter-gestural coordination for children with speech sound disorders (SSD) subsequent to Prompts for Restructuring Oral and Muscular Phonetic Targets (PROMPT) intervention. We measured the distribution patterns of voice onset time (VOT) for a voiceless stop (/p/) to examine the changes in inter-gestural coordination. Two standardized tests were used (Verbal Motor Production Assessment for Children (VMPAC), GFTA-2) to assess the changes in motor speech skills and articulation. Data showed positive changes in patterns of VOT with a lower pattern of variability. All children showed significantly higher scores for VMPAC, but only some children showed higher scores for GFTA-2. Results suggest that the proprioceptive feedback provided through PROMPT had a positive influence on speech motor control and inter-gestural coordination in voicing behavior. This set of VOT data for children with SSD adds to our understanding of the speech characteristics underlying speech motor control. Directions for future studies are discussed.

A powerful metric for expressive language lateralization in MEG.

Magnetoencephalography (MEG) has proven valuable for presurgical language lateralization. Investigators have established that low-beta (13-23 Hz) event-related desynchrony (ERD), a neuromagnetic signature for increased neuronal firing, maps to critical language centers for expressive language tasks in MEG. The distribution of low-beta ERD is relatively bilateral in early childhood, transitioning to left lateralized by adolescence or early adulthood. Recently, we showed that a complementary signal, low-beta event-related synchrony, thought to reflect neuronal inhibition, becomes increasingly right lateralized across development. Here, we introduce a hybrid laterality index for language derived from both low-beta ERD and ERS. We present findings from a large cohort of children performing verb generation in MEG, and show that inclusion of low-beta ERS provides relatively powerful estimation of language lateralization.

Virtual lesions in MEG reveal increasing vulnerability of the language network from early childhood through adolescence.

In childhood, language outcomes following brain injury are inversely related to age. Neuroimaging findings suggest that extensive representation and/or topological redundancy may confer the pediatric advantage. Here, we assess whole brain and language network resilience using in silico attacks, for 85 children participating in a magnetoencephalography (MEG) study. Nodes are targeted based on eigenvector centrality, betweenness centrality, or at random. The size of each connected component is assessed after iterated node removal; the percolation point, or moment of dis-integration, is defined as the first instance where the second largest component peaks in size. To overcome known effects of fixed thresholding on subsequent graph and resilience analyses, we study percolation across all possible network densities, within a Functional Data Analysis (FDA) framework. We observe age-related increases in vulnerability for random and betweenness centrality-based attacks for whole-brain and stories networks (adjusted-p < 0.05). Here we show that changes in topology underlie increasing language network vulnerability in development.

Age-related increases in right hemisphere support for prosodic processing in children.

Language comprehension is a complex process involving an extensive brain network. Brain regions responsible for prosodic processing have been studied in adults; however, much less is known about the neural bases of prosodic processing in children. Using magnetoencephalography (MEG), we mapped regions supporting speech envelope tracking (a marker of prosodic processing) in 80 typically developing children, ages 4-18 years, completing a stories listening paradigm. Neuromagnetic signals coherent with the speech envelope were localized using dynamic imaging of coherent sources (DICS). Across the group, we observed coherence in bilateral perisylvian cortex. We observed age-related increases in coherence to the speech envelope in the right superior temporal gyrus (r = 0.31, df = 78, p = 0.0047) and primary auditory cortex (r = 0.27, df = 78, p = 0.016); age-related decreases in coherence to the speech envelope were observed in the left superior temporal gyrus (r = - 0.25, df = 78, p = 0.026). This pattern may indicate a refinement of the networks responsible for prosodic processing during development, where language areas in the right hemisphere become increasingly specialized for prosodic processing. Altogether, these results reveal a distinct neurodevelopmental trajectory for the processing of prosodic cues, highlighting the presence of supportive language functions in the right hemisphere. Findings from this dataset of typically developing children may serve as a potential reference timeline for assessing children with neurodevelopmental hearing and speech disorders.

Correlation of NICU anthropometry in extremely preterm infants with brain development and language scores at early school age.

Growth in preterm infants in the neonatal intensive care unit (NICU) is associated with increased global and regional brain volumes at term, and increased postnatal linear growth is associated with higher language scores at age 2. It is unknown whether these relationships persist to school age or if an association between growth and cortical metrics exists. Using regression analyses, we investigated relationships between the growth of 42 children born extremely preterm (< 28 weeks gestation) from their NICU hospitalization, standardized neurodevelopmental/language assessments at 2 and 4-6 years, and multiple neuroimaging biomarkers obtained from T1-weighted images at 4-6 years. We found length at birth and 36 weeks post-menstrual age had positive associations with language scores at 2 years in multivariable linear regression. No growth metric correlated with 4-6 year assessments. Weight and head circumference at 36 weeks post-menstrual age positively correlated with total brain volume and negatively with global cortical thickness at 4-6 years of age. Head circumference relationships remained significant after adjusting for age, sex, and socioeconomic status. Right temporal cortical thickness was related to receptive language at 4-6 years in the multivariable model. Results suggest growth in the NICU may have lasting effects on brain development in extremely preterm children.

Altered white matter connectivity in children with congenital heart disease with single ventricle physiology.

Children born with congenital heart disease (CHD) have seen a dramatic decrease in mortality thanks to surgical innovations. However, there are numerous risk factors associated with CHD that can disrupt neurodevelopment. Recent studies have found that psychological deficits and structural brain abnormalities persist into adulthood. The goal of the current study was to investigate white matter connectivity in early school-age children (6-11 years), born with complex cyanotic CHD (single ventricle physiology), who have undergone Fontan palliation, compared to a group of heart-healthy, typically developing controls (TPC). Additionally, we investigated associations between white matter tract connectivity and measures on a comprehensive neuropsychological battery within each group. Our results suggest CHD patients exhibit widespread decreases in white matter connectivity, and the extent of these decreases is related to performance in several cognitive domains. Analysis of network topology showed that hub distribution was more extensive and bilateral in the TPC group. Our results are consistent with previous studies suggesting perinatal ischemia leads to white matter lesions and delayed maturation.

Tolerability of transcranial magnetic stimulation language mapping in children.

OBJECTIVE: Transcranial Magnetic Stimulation (TMS) has emerged as a viable non-invasive method for mapping language networks. Little is known about the tolerability of transcranial magnetic stimulation language mapping in children. METHODS: Children aged 5-18 years underwent bilateral language mapping using repetitive transcranial magnetic stimulation (rTMS) to target 33 sites/hemisphere. Stimulation was delivered at 5 Hz, in 1-2 second bursts, during visual naming and auditory verb generation. Pain unpleasantness and pain intensity were assessed using an unpleasantness visual analog scale (VAS). RESULTS: 49 participants tolerated motor mapping and had repetitive transcranial magnetic stimulation. 35/49 (71%) completed visual naming and 26/49 (53%) completed both visual naming and verb generation. Mean electrical field per participant was 115 V/m. Young age and lower language ability were associated with lower completion. Visual analogue scale scores were significantly higher (6.1 vs. 2.8) in participants who withdrew early compared to those who completed at least visual naming. CONCLUSIONS: Pain measured by VAS was a major contributor to early withdrawal. However, a complete bilateral map was obtained with one paradigm in 71% of participants. Future studies designed to reduce pain during repetitive transcranial magnetic stimulation over language cortex will boost viability. SIGNIFICANCE: This study represents the first attempt to characterize tolerability of bilateral repetitive transcranial magnetic stimulation language mapping in healthy children.

Quality of life in young adults who underwent resective surgery for epilepsy in childhood.

PURPOSE: This study investigated quality of life (QOL) in young adults who had undergone epilepsy surgery before the age of 16 years. The contribution to QOL of seizure status in the prior year, sex, number of antiepileptic drugs, and mood were evaluated. METHODS: Sixty-nine young adults who had undergone surgery were subdivided into those who were seizure-free in the past year (n = 38) and those who had seizures (n = 31) in that time. A nonsurgical comparison group of young adults (n = 29) with childhood-onset medically intractable epilepsy was also studied. All groups completed measures of QOL and mood. KEY FINDINGS: After accounting for mood, sex, and number of antiepileptic drugs, the seizure-free group reported better cognitive and physical function and overall QOL, experienced less seizure worry, and had better self-perception. Mood was the most consistently predictive covariate, and was independently predictive of many aspects of QOL. SIGNIFICANCE: Seizure freedom associated with surgery in childhood is associated with improved QOL in certain domains. Findings highlight the importance of mood in determining self-perception of QOL.

Cross-Frequency Coupling in Childhood Absence Epilepsy.

Objective: Absence seizures are the prototypic primarily generalized seizures, but there is incomplete understanding regarding their generation and maintenance. A core network for absence seizures has been defined, including focal cortical and thalamic regions that have frequency-dependent interactions. The purpose of this study was to investigate within-frequency coupling and cross-frequency coupling (CFC) during human absence seizures, to identify key regions (hubs) within the absence network that contribute to propagation and maintenance. Methods: Thirteen children with new-onset and untreated childhood absence epilepsy had over 60 typical absence seizures during both electroencephalography-functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) recordings. The spatial map of the ictal network was defined using fMRI and used as prior information for MEG connectivity. A multilayer network approach was used to investigate within-frequency coupling and CFC for canonical frequency bands. A rigorous null-modeling approach was used to determine connections outside the noise floor. Results: Strong coupling between beta and gamma frequencies, within the left frontal cortex, and between the left frontal and right parietal regions was observed. There was also strong connectivity between left frontal and right parietal nodes within the gamma band. Multilayer versatility analysis identified a cluster of network hubs in the left frontal region. Interpretation: Cortical regions commonly identified as being critical for absence seizure generation (frontal cortex, precuneus) have strong CFC and within-frequency coupling between beta and gamma bands. As nonpharmacologic treatments, such as neuromodulation, become available for generalized epilepsies, detailed mechanistic understanding of how "diffuse" seizures are generated and maintained will be necessary to provide optimal outcomes.

Extracallosal Structural Connectivity Is Positively Associated With Language Performance in Well-Performing Children Born Extremely Preterm.

Children born extremely preterm (<28 weeks gestation) are at risk for language delay or disorders. Decreased structural connectivity in preterm children has been associated with poor language outcome. Previously, we used multimodal imaging techniques to demonstrate that increased functional connectivity during a stories listening task was positively associated with language scores for preterm children. This functional connectivity was supported by extracallosal structural hyperconnectivity when compared to term-born children. Here, we attempt to validate this finding in a distinct cohort of well-performing extremely preterm children (EPT, n = 16) vs. term comparisons (TC, n = 28) and also compare this to structural connectivity in a group of extremely preterm children with a history of language delay or disorder (EPT-HLD, n = 8). All participants are 4-6 years of age. We perform q-space diffeomorphic reconstruction and functionally-constrained structural connectometry (based on fMRI activation), including a novel extension enabling between-groups comparisons with non-parametric ANOVA. There were no significant differences between groups in age, sex, race, ethnicity, parental education, family income, or language scores. For EPT, tracks positively associated with language scores included the bilateral posterior inferior fronto-occipital fasciculi and bilateral cerebellar peduncles and additional cerebellar white matter. Quantitative anisotropy in these pathways accounted for 55% of the variance in standardized language scores for the EPT group specifically. Future work will expand this cohort and follow longitudinally to investigate the impact of environmental factors on developing language networks and resiliency in the preterm brain.