Diffuse excessive high signal intensity in the preterm brain on advanced MRI represents widespread neuropathology.

Preterm brains commonly exhibit elevated signal intensity in the white matter on T2-weighted MRI at term-equivalent age. This signal, known as diffuse excessive high signal intensity (DEHSI) or diffuse white matter abnormality (DWMA) when quantitatively assessed, is associated with abnormal microstructure on diffusion tensor imaging. However, postmortem data are largely lacking and difficult to obtain, and the pathological significance of DEHSI remains in question. In a cohort of 202 infants born preterm at ≤32 weeks gestational age, we leveraged two newer diffusion MRI models - Constrained Spherical Deconvolution (CSD) and neurite orientation dispersion and density index (NODDI) - to better characterize the macro and microstructural properties of DWMA and inform the ongoing debate around the clinical significance of DWMA. With increasing DWMA volume, fiber density broadly decreased throughout the white matter and fiber cross-section decreased in the major sensorimotor tracts. Neurite orientation dispersion decreased in the centrum semiovale, corona radiata, and temporal lobe. These findings provide insight into DWMA's biological underpinnings and demonstrate that it is a serious pathology.

Longer Screen Vs. Reading Time is Related to Greater Functional Connections Between the Salience Network and Executive Functions Regions in Children with Reading Difficulties Vs. Typical Readers.

An adverse relationship between screen exposure time and brain functional/structural connectivity was reported in typically developing children, specifically related to neurobiological correlates of reading ability. As children with reading difficulties (RD) suffer from impairments in reading and executive functions (EF), we sought to determine the association between the ratio of screen time duration to reading time duration and functional connectivity of EF networks to the entire brain in children with RD compared to typical readers (TRs) using resting state data. Screen/reading time ratio was related to reduced reading and EF abilities. A larger screen/reading time ratio was correlated with increased functional connectivity between the salience network and frontal-EF regions in children with RD compared to TRs. We suggest that whereas greater screen/reading time ratio is related to excessive stimulation of the visual processing system in TRs, it may be related to decreased efficiency of the cognitive control system in RDs.

Maternal reading and fluency abilities are associated with diffusion properties of ventral and dorsal white matter tracts in their preschool-age children.

Early language exposure and shared parent-child reading, as assessed by maternal reading ability and fluency, affect the child's future language and cognitive abilities. The aim of the current study was to explore the association between maternal reading ability and fluency and diffusion properties of language- and cognition-related white matter tracts in their pre-school age children using diffusion tensor imaging (DTI). DTI data were acquired from fifteen girls (mean age: 3.83 ± 0.49 years). Reading ability and fluency were assessed in their mothers. Effects of hemisphere and node on diffusion properties were measured at 100 points along white matter tracts related to language and cognitive abilities. Significant positive correlations were found between maternal reading ability and fractional anisotropy in left and right dorsal and ventral language and executive functions-related tracts, while maternal reading fluency was associated with higher fractional anisotropy in ventral tracts, mainly in the left hemisphere. Fractional Anisotropy was significantly higher in the left compared to the right arcuate, cingulum cingulate, and inferior longitudinal fasciculus and higher in the right compared to the left superior longitudinal fasciculus. Our results signify the importance of maternal reading as a facilitator of the child's future language and cognitive abilities.

Maternal reading fluency is associated with functional connectivity between the child's future reading network and regions related to executive functions and language processing in preschool-age children.

Reading is an acquired skill that relies on cognitive-control and language abilities. Home reading environment has been positively correlated with activation in parietal-temporal-occipital association cortex supporting mental imagery and narrative comprehension during a story-listening task in preschool-age children. However, the degree to which maternal reading ability influences early brain development, specifically neural circuits involved with language and reading, is not well understood. The current study explored the relationship between maternal reading ability and functional connectivity within the language network, between the language network and networks related to cognitive control and visual processing, as well as between the language network and the entire brain (network-to-voxel analysis) of preschool-age children during a resting state. Thirteen 4-year-old girls and their mothers participated in this study, involving cognitive testing and functional magnetic resonance imaging, including a resting-state scan. Maternal reading ability was negatively correlated with functional connectivity within the child's language network at rest, and also with areas involved in visual processing, cognitive-control, and semantics. These results suggest that children whose mothers exhibit decreased reading ability may demonstrate a greater engagement of the language network and neural circuits related to visual word recognition, cognitive-control, and semantic processing, which later in life support reading.

Relative Head Impact Exposure and Brain White Matter Alterations After a Single Season of Competitive Football: A Pilot Comparison of Youth Versus High School Football.

OBJECTIVE: Youth athletes are believed to be more susceptible to white matter (WM) degradation resulting from head impact exposure relative to high school (HS) athletes; this hypothesis has not been objectively tested. The purpose of this study was to determine preseason to postseason changes in WM integrity from repetitive head impacts for youth football (YFB) players compared with HS football players during a competitive football season. DESIGN: Prospective cohort. SETTING: One season of YFB (grades 7 and 8) and varsity HS football (grades 10-12). PATIENTS OR OTHER PARTICIPANTS: Twelve YFB (13.08 ± 0.64 years) and 21 HS (17.5 ± 0.78 years) athletes. INTERVENTIONS: Participants completed 2 magnetic resonance imaging sessions: preseason and postseason. Head impact exposure was recorded during practice and games using a helmet-mounted accelerometer. MAIN OUTCOME MEASURES: Tract-based spatial statistics were used to evaluate group differences in preseason to postseason changes in diffusion tensor imaging, including fractional anisotropy and mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). RESULTS: The HS group exhibited significant preseason to postseason reductions in MD, AD, and RD (P < 0.05, corrected) in widespread WM areas. Significant WM reductions for the YFB group were only observed for AD (P < 0.05, corrected), but was more limited in extent compared with HS. CONCLUSIONS: Significant preseason to postseason AD reduction was found in both YFB and HS groups after one season of competitive play. Our results did not confirm recent speculation that younger children are more susceptible to the deleterious effects of repetitive head impacts compared with their older counterparts.

Reduced Cortico-Cortical Resting-State Connectivity in Sensory Systems Related to Bodily Pain in Juvenile Fibromyalgia.

OBJECTIVE: Juvenile-onset fibromyalgia (JFM) is a paradigmatic chronic pain condition for which the underlying neurobiological substrates are poorly understood. This study examined, for the first time, data-driven resting-state functional connectivity (rsFC) alterations in 37 female adolescents with JFM compared with 43 healthy female adolescents and identified associations with bodily pain. METHODS: Whole-brain voxel-wise rsFC alterations were assessed using the intrinsic connectivity contrast, a measure of node centrality at each voxel, and seed-based analyses for interpretability. We studied the relationship between rsFC alterations in somatosensory systems and the location and extension of bodily pain. RESULTS: Adolescents with JFM had voxel-wise rsFC reductions in the paracentral lobule (PCL)/primary somatosensory cortex (S1) (T = 4.89, family-wise error corrected p-value (pFWE) < 0.001) and left midcingulate cortex (T = 4.67, pFWE = 0.043). Post hoc analyses revealed reduced rsFC spanning major cortical sensory hubs (T > 4.4, pFWE < 0.030). Cortico-cortical rsFC reductions within PCL/S1 in JFM occurred in locations innervated by bodily areas where the pain was most frequent (F = 3.15; positive false discovery rate = 0.029) and predicted widespread pain (T > 4.4, pFWE < 0.045). Conversely, adolescents with JFM had increases in PCL/S1-thalamus (T = 4.75, pFWE = 0.046) and PCL/S1-anterior insula rsFC (T = 5.13, pFWE = 0.039). CONCLUSION: Reduced cortico-cortical sensory integration involving PCL/S1 and spanning the sensory systems may underly critical pain sensory features in youth with JFM. Reduced sensory integration is paralleled by augmented cross-talk between sensory and affective/salience-processing regions, potentially indicating a shift toward more affectively colored sensory experiences to the detriment of specific sensory discrimination.

Neurophysiology of Resilience in Juvenile Fibromyalgia.

Objective: Juvenile fibromyalgia (JFM) is a chronic pain syndrome predominantly affecting adolescent girls. Resilience may be a protective factor in coping with pain, reducing affective burden, and promoting positive outlooks. Brain regions affected in JFM overlap with those linked to resilience, particularly in the default-mode network (DMN). We investigate the role of resilience on core somatic and affective symptoms in JFM and assess the neurophysiological substrates for the first time. Methods: Forty-one girls with JFM and 40 pain-free adolescents completed a resting-state fMRI assessment and self-report questionnaires. We used clustering analyses to group JFM participants based on resilience, and principal component analyses to summarize core somatic and affective symptoms. We estimated whole-brain and within-DMN connectivity and assessed differences between higher and lower resilience JFM groups and compared their connectivity patterns to pain-free participants. Results: The higher resilience JFM group had less affective (T=4.03; p<.001) but similar core somatic symptoms (T=1.05; p=.302) than the lower resilience JFM group. They had increased whole-brain (T's>3.90, pFDR's<.03) and within-DMN (T=2.20, p=.03) connectivity strength, and higher connectivity between DMN nodes and self-referential, regulatory, and reward-processing regions. Conversely, higher DMN-premotor connectivity was observed in the lower resilience group. Conclusion: JFM participants with higher resilience were protected affectively but not in core somatic symptoms. Greater resilience was accompanied by higher signal integration within the DMN, a network central to internally oriented attention and flexible attention shifting. Crucially, the connectivity pattern in highly resilient patients resembled that of pain-free adolescents, which was not the case for the lower resilience group.

Machine Learning Classification of Verified Head Impact Exposure Strengthens Associations with Brain Changes.

Cumulative exposure to head impacts during contact sports can elicit potentially deleterious brain white matter alterations in young athletes. Head impact exposure is commonly quantified using wearable sensors; however, these sensors tend to overestimate the number of true head impacts that occur and may obfuscate potential relationships with longitudinal brain changes. The purpose of this study was to examine whether data-driven filtering of head impact exposure using machine learning classification could produce more accurate quantification of exposure and whether this would reveal more pronounced relationships with longitudinal brain changes. Season-long head impact exposure was recorded for 22 female high school soccer athletes and filtered using three methods-threshold-based, heuristic filtering, and machine learning (ML) classification. The accuracy of each method was determined using simultaneous video recording of a subset of the sensor-recorded impacts, which was used to confirm which sensor-recorded impacts corresponded with true head impacts and the ability of each method to detect the true impacts. Each filtered dataset was then associated with the athletes' pre- and post-season MRI brain scans to reveal longitudinal white matter changes. The threshold-based, heuristic, and ML approaches achieved 22.0% accuracy, 44.6%, and 83.5% accuracy, respectively. ML classification also revealed significant longitudinal brain white matter changes, with negative relationships observed between head impact exposure and reductions in mean and axial diffusivity and a positive relationship observed between exposure and fractional anisotropy (all p < 0.05).

Diffusion Tensor Imaging in Athletes Sustaining Repetitive Head Impacts: A Systematic Review of Prospective Studies.

Competitive sport participation, in contact and collision sports, exposes athletes to repetitive head impacts. Although these impacts do not always result in overt symptomology or a diagnosed "concussion," evidence indicates that cumulative repetitive impacts affect brain pathophysiology. The purpose of this study was to perform a systematic review of prospective, longitudinal trials evaluating repetitive head impact exposure on white matter (WM) microstructure in collision and contact sport athletes to inform clinical care and treatment strategies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to determine studies that met predetermined inclusion and exclusion criteria. Initially, 2498 abstracts were identified, and 20 studies were critically evaluated herein. The majority of studies demonstrated significant longitudinal changes in anisotropy and/or diffusivity metrics that were associated with the quantity and/or the magnitude of head impact exposure, highlighting the utility of diffusion tensor imaging (DTI) for measuring changes in WM microstructure. Our review also comments on study methodology and describes how age, sex, sport, and time between sport cessation and DTI measures contribute to divergent findings within the literature. Suggestions for future research are also provided to overcome previous study limitations and maximize our understanding of the role of repetitive head impact exposure on WM integrity and long-term neurological sequela.