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.

An iPad-based intervention to improve visual-motor, visual-attention, and visual-perceptual skills in children with surgically treated hydrocephalus: A pilot study.

PURPOSE: Develop and pilot an iPad-based intervention for improving visual-motor coordination, visual-spatial processing/reasoning, and visual attention in children with surgically treated hydrocephalus (HCP). METHODS: We developed an intervention protocol targeting visual-motor coordination, visual-spatial processing/reasoning, and visual attention. Fourteen participants with HCP completed 30 h of training over 6 weeks. The primary outcome measure was the Perceptual Reasoning Index from the Wechsler Abbreviated Scale of Intelligence, Second Edition. Secondary measures included subtests from the Wechsler Intelligence Scale for Children, Fourth Edition, Developmental NEuroPSYchological Assessment, Second Edition (NEPSY-II), and Purdue Pegboard. RESULTS: Children with HCP demonstrated gains with statistical significance on the Perceptual Reasoning Index. We also observed significant improvement on a timed test of visuo-motor coordination (Wechsler Intelligence Scale for Children, Fourth Edition, Coding). CONCLUSION: Our iPad-application-based intervention may promote visual-motor coordination, visual-spatial processing/reasoning, and visual attention skills in children with HCP, offering an engaging and economical supplement to more conventional therapies.

Association between brain structural network efficiency at term-equivalent age and early development of cerebral palsy in very preterm infants.

Very preterm infants (born at less than 32 weeks gestational age) are at high risk for serious motor impairments, including cerebral palsy (CP). The brain network changes that antecede the early development of CP in infants are not well characterized, and a better understanding may suggest new strategies for risk-stratification at term, which could lead to earlier access to therapies. Graph theoretical methods applied to diffusion MRI-derived brain connectomes may help quantify the organization and information transfer capacity of the preterm brain with greater nuance than overt structural or regional microstructural changes. Our aim was to shed light on the pathophysiology of early CP development, before the occurrence of early intervention therapies and other environmental confounders, to help identify the best early biomarkers of CP risk in VPT infants. In a cohort of 395 very preterm infants, we extracted cortical morphometrics and brain volumes from structural MRI and also applied graph theoretical methods to diffusion MRI connectomes, both acquired at term-equivalent age. Metrics from graph network analysis, especially global efficiency, strength values of the major sensorimotor tracts, and local efficiency of the motor nodes and novel non-motor regions were strongly inversely related to early CP diagnosis. These measures remained significantly associated with CP after correction for common risk factors of motor development, suggesting that metrics of brain network efficiency at term may be sensitive biomarkers for early CP detection. We demonstrate for the first time that in VPT infants, early CP diagnosis is anteceded by decreased brain network segregation in numerous nodes, including motor regions commonly-associated with CP and also novel regions that may partially explain the high rate of cognitive impairments concomitant with CP diagnosis. These advanced MRI biomarkers may help identify the highest risk infants by term-equivalent age, facilitating earlier interventions that are informed by early pathophysiological changes.

The effects of internal jugular vein compression for modulating and preserving white matter following a season of American tackle football: A prospective longitudinal evaluation of differential head impact exposure.

The purpose of this clinical trial was to examine whether internal jugular vein compression (JVC)-using an externally worn neck collar-modulated the relationships between differential head impact exposure levels and pre- to postseason changes in diffusion tensor imaging (DTI)-derived diffusivity and anisotropy metrics of white matter following a season of American tackle football. Male high-school athletes (n = 284) were prospectively assigned to a non-collar group or a collar group. Magnetic resonance imaging data were collected from participants pre- and postseason and head impact exposure was monitored by accelerometers during every practice and game throughout the competitive season. Athletes' accumulated head impact exposure was systematically thresholded based on the frequency of impacts of progressively higher magnitudes (10 g intervals between 20 to 150 g) and modeled with pre- to postseason changes in DTI measures of white matter as a function of JVC neck collar wear. The findings revealed that the JVC neck collar modulated the relationships between greater high-magnitude head impact exposure (110 to 140 g) and longitudinal changes to white matter, with each group showing associations that varied in directionality. Results also revealed that the JVC neck collar group partially preserved longitudinal changes in DTI metrics. Collectively, these data indicate that a JVC neck collar can provide a mechanistic response to the diffusion and anisotropic properties of brain white matter following the highly diverse exposure to repetitive head impacts in American tackle football. Clinicaltrials.gov: NCT# 04068883.

Altered frontal-mediated inhibition and white matter connectivity in pediatric chronic tic disorders.

Tics are unique from most movement disorders, in that they are partially suppressible. As part of the inhibitory motor network, the pre-supplementary motor area is engaged in motor control and may be involved in tic physiology. We used dual-site transcranial magnetic stimulation to assess inhibitory connectivity between right pre-supplementary motor area and left primary motor cortex, which has previously been demonstrated in healthy adults. We also used diffusion tensor imaging to investigate white matter connectivity in children with chronic tics. Twelve children with chronic tic disorder and fourteen typically developing controls underwent MRI with diffusion tensor imaging indices analysis followed by single and paired-pulse transcranial magnetic stimulation with conditioning pulse over the right pre-supplementary motor area followed by left motor cortex test pulse. Neurophysiologic and imaging data relationships to measures of tic severity and suppressibility were also evaluated in tic patients. Pre-supplementary motor area-mediated inhibition of left motor cortex was present in healthy control children but not in chronic tic disorder participants. Less inhibition correlated with worse tic suppressibility (ρ = - 0.73, p = 0.047). Imaging analysis showed increased fractional anisotropy in the right superior longitudinal fasciculus, corpus callosum, corona radiata and posterior limb of the internal capsule (p < 0.05) in tic participants, which correlated with lower self-reported tic suppressibility (ρ = - 0.70, p = 0.05). Physiologic data revealed impaired frontal-mediated motor cortex inhibition in chronic tic participants, and imaging analysis showed abnormalities in motor pathways. Collectively, the neurophysiologic and neuroanatomic data correlate with tic suppressibility, supporting the relevancy to tic pathophysiology.

Effects of intraventricular hemorrhage on white matter microstructural changes at term and early developmental outcomes in infants born very preterm.

PURPOSE: Very preterm (VPT) infants are at high risk for motor and behavioral deficits. We investigated microstructural differences using diffusion tensor imaging (DTI) among VPT infants with different grades of intraventricular hemorrhage (IVH), their association with early motor function and temperament ratings, and the potential moderating effect of IVH severity on the above structure-function relations. METHODS: Fifty-seven VPT (≤32 weeks gestational age) infants with IVH (Low Grade (Papile grading I/II): 42; High Grade (III/IV): 15) were studied. DTI was acquired between 39 and 44 weeks postmenstrual age and was analyzed using the tract-based spatial statistics approach. Early motor function and temperament were assessed at 3-month corrected age based on the Hammersmith Infant Neurological Examination (HINE) and Infant Behavioral Questionnaire - Revised, Short Version (IBQ-R-S), respectively. RESULTS: Significantly lower fractional anisotropy and higher mean, axial, and/or radial diffusivity were found in VPT infants with High Grade IVH compared to Low Grade IVH (p < 0.05). Significant associations were found between DTI metrics and motor function in both IVH groups and between DTI and Fear temperament ratings in the High Grade IVH Group (all p < 0.05). IVH severity had a significant moderating effect on the relation between DTI and motor and Fear ratings (p < 0.05). CONCLUSION: DTI is a sensitive neuroimaging biomarker providing a refined understanding of the impact and location of differing severities of IVH on the developing white matter of VPT infants. Early motor and behavioral outcomes are associated with microstructural changes that are influenced by severity of IVH.

Abnormal anisotropic diffusion properties in pediatric myelomeningocele patients treated with fetal surgery: an initial DTI study.

PURPOSE: To investigate white matter microstructural abnormality based on diffusion tensor imaging (DTI) in pediatric patients with fetal repair for myelomeningocele (MMC). METHODS: This was a retrospective analysis of DTI data from 8 pediatric patients with prenatal MMC repair (age range 1.64-33.70 months; sex 3F/5M) and 8 age-matched controls (age 2.24-31.20 months; sex 5F/2M). All participants were scanned on 1.5T GE Signa MR scanner (GE Healthcare, Milwaukee, WI) with the same sequence specifications. Two DTI measures, including fractional anisotropy (FA) and mean diffusivity (MD), were calculated from the genu of corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). DTI values and fronto-occipital horn ratio (FOHR) were tested for group difference based on two-tailed paired t test. RESULTS: The ventricle size based on FOHR in patients with prenatal MMC repair was significantly larger than that in the age-matched control group (p < 0.001). Statistically significant group difference in DTI (lower FA and higher MD in patient group) was found in gCC (p = 0.007 and 0.003, respectively). A trend level increase in MD was also found (p = 0.065) in PLIC in patients when compared with the age-matched controls. CONCLUSION: Our data showed white matter abnormality based on DTI in pediatric patient with fetal repair for MMC. The sensitivity of DTI in detecting white matter abnormality, as shown in the present study, may help to serve as an imaging biomarker for assessing hydrocephalus and improve and optimize decision making for the treatment of hydrocephalus in this patient population.

Neonatal Functional and Structural Connectivity Are Associated with Cerebral Palsy at Two Years of Age.

OBJECTIVE: The accuracy of structural magnetic resonance imaging (MRI) to predict later cerebral palsy (CP) in newborns with perinatal brain injury is variable. Diffusion tensor imaging (DTI) and task-based functional MRI (fMRI) show promise as predictive tools. We hypothesized that infants who later developed CP would have reduced structural and functional connectivity as compared with those without CP. STUDY DESIGN: We performed DTI and fMRI using a passive motor task at 40 to 48 weeks' postmenstrual age in 12 infants with perinatal brain injury. CP was diagnosed at age 2 using a standardized examination. RESULTS: Five infants had CP at 2 years of age, and seven did not have CP. Tract-based spatial statistics showed a widespread reduction of fractional anisotropy (FA) in almost all white matter tracts in the CP group. Using the median FA value in the corticospinal tracts as a cutoff, FA was 100% sensitive and 86% specific to predict CP compared with a sensitivity of 60 to 80% and a specificity of 71% for structural MRI. During fMRI, the CP group had reduced functional connectivity from the right supplemental motor area as compared with the non-CP group. CONCLUSION: DTI and fMRI obtained soon after birth are potential biomarkers to predict CP in newborns with perinatal brain injury.

Examining Motor Tasks of Differing Complexity After Concussion in Adolescents.

OBJECTIVES: (1) To determine the effects of concussion-related motor impairments at different task complexities in isolation and with a cognitive dual-task and (2) to determine if self-reported balance deficits after concussion are associated with gait, quiet stance, or cognitive dual-task impairments. DESIGN: Cross-sectional study. SETTING: Sports medicine clinic. PARTICIPANTS: Adolescent athletes clinically diagnosed with a sport-related concussion and those without concussion. Forty-nine patients with concussion (mean age=14.9±1.9y; 51% female; tested 7.0±3.0d postinjury) and 65 control participants (mean age=14.9±1.6y; 52% female) completed the study (N=114). INTERVENTIONS: Athletes with concussion completed a single-task and dual-task standing and walking protocol within 14 days of injury and were compared to those without concussion. MAIN OUTCOME MEASURES: Outcome measures included gait speed, quiet stance (root mean square [RMS] coronal/sagittal plane sway), and cognitive performance (accuracy). Dual-task costs were calculated as the percentage change between single-task and dual-task conditions. Participants with concussion were then stratified by those who did and did not report subjective balance problems at the time of testing and compared using objective balance and gait metrics. RESULTS: The concussion group walked slower during dual-task gait than controls (0.83±0.17 m/s vs 0.92±0.15 m/s; Cohen's d=0.53). Dual-task quiet stance RMS sway values were similar for concussion and control groups in coronal (1.20±0.52 m/s-2 vs 1.26±0.65 m/s-2; d=0.09) and sagittal (0.56±0.24 m/s-2 vs 0.73±0.44 m/s-2; d=0.20) movement planes. The concussion participants with subjectively-reported balance problems had significantly greater walking speed dual-task costs than concussion participants without self-reported balance problems (-25±10% vs -19±9%; P=.02). CONCLUSIONS: Following concussion, adolescents demonstrate slower gait speeds, but similar quiet stance values relative to those without concussion. The study results indicate that tasks requiring greater motor coordination may elicit greater alterations following a concussion.

Altered brain microstructure in association with repetitive subconcussive head impacts and the potential protective effect of jugular vein compression: a longitudinal study of female soccer athletes.

PURPOSE: To (1) quantify white matter (WM) alterations in female high school athletes during a soccer season and characterise the potential for normalisation during the off-season rest period, (2) determine the association between WM alterations and exposure to repetitive subconcussive head impacts, and (3) evaluate the efficacy of a jugular vein compression collar to prevent WM alterations associated with head impact exposure. METHODS: Diffusion tensor imaging (DTI) data were prospectively collected from high school female soccer participants (14-18 years) at up to three time points over 9 months. Head impacts were monitored using accelerometers during all practices and games. Participants were assigned to a collar (n=24) or non-collar group (n=22). The Tract-Based Spatial Statistics approach was used in the analysis of within-group longitudinal change and between-group comparisons. RESULTS: DTI analyses revealed significant pre-season to post-season WM changes in the non-collar group in mean diffusivity (2.83%±2.46%), axial diffusivity (2.58%±2.34%) and radial diffusivity (3.52%±2.60%), but there was no significant change in the collar group despite similar head impact exposure. Significant correlation was found between head impact exposure and pre-season to post-season DTI changes in the non-collar group. WM changes in the non-collar group partially resolved at 3 months off-season follow-up. DISCUSSION: Microstructural changes in WM occurred during a season of female high school soccer among athletes who did not wear the collar device. In comparison, there were no changes in players who wore the collar, suggesting a potential prophylactic effect of the collar device in preventing changes associated with repetitive head impacts. In those without collar use, the microstructural changes showed a reversal towards normal over time in the off-season follow-up period.

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.

White matter alterations over the course of two consecutive high-school football seasons and the effect of a jugular compression collar: A preliminary longitudinal diffusion tensor imaging study.

The cumulative effects of repetitive subclinical head impacts during sports may result in chronic white matter (WM) changes and possibly, neurodegenerative sequelae. In this pilot study, we investigated the longitudinal WM changes over the course of two consecutive high-school football seasons and explored the long-term effects of a jugular vein compression collar on these WM alterations. Diffusion tensor imaging data were prospectively collected both pre- and postseason in the two consecutive seasons. Participants were assigned into either collar or noncollar groups. Tract-based spatial statistics (TBSS) approach and region of interest-based approach were used to quantify changes in WM diffusion properties. Despite comparable exposure to repetitive head impacts, significant reductions in mean, axial, and/or radial diffusivity were identified in Season 1 in multiple WM regions in the noncollar group but not in the collar group. After an 8- to 9-month long off-season, these changes observed in the noncollar group partially and significantly reversed but also remained significantly different from the baseline. In Season 2, trend level WM alterations in the noncollar group were found but located in spatially different regions than Season 1. Last, the WM integrity in the collar group remained unchanged throughout the four time points. In conclusion, we quantitatively assessed the WM structural changes and partial reversal over the course of two consecutive high-school football seasons. In addition, the mitigated WM alterations in athletes in the collar group might indicate potential effect of the collar in ameliorating the changes against repetitive head impacts. Hum Brain Mapp 39:491-508, 2018. © 2017 Wiley Periodicals, Inc.

A jugular vein compression collar prevents alterations of endogenous electrocortical dynamics following blast exposure during special weapons and tactical (SWAT) breacher training.

Exposure to explosive blasts places one at risk for traumatic brain injury, especially for special weapons and tactics (SWAT) and military personnel, who may be repeatedly exposed to blasts. In the current study, the effectiveness of a jugular vein compression collar to prevent alterations in resting-state electrocortical activity following a single-SWAT breacher training session was investigated. SWAT team personnel were randomly assigned to wear a compression collar during breacher training and resting state electroencephalography (EEG) was measured within 2 days prior to and two after breacher training. It was hypothesized that significant changes in brain dynamics-indicative of possible underlying neurodegenerative processes-would follow blast exposure for those who did not wear the collar, with ameliorated changes for the collar-wearing group. Using recurrence quantification analysis (RQA) it was found that participants who did not wear the collar displayed longer periods of laminar electrocortical behavior (as indexed by RQA's vertical max line measure) after breacher training. It is proposed that the blast wave exposure for the no-collar group may have reduced the number of pathways, via axonal disruption-for electrical transmission-resulting in the EEG signals becoming trapped in laminar states for longer periods of time. Longer laminar states have been associated with other electrocortical pathologies, such as seizure, and may be important for understanding head trauma and recovery.

Brain-Behavior Mechanisms for the Transfer of Neuromuscular Training Adaptions to Simulated Sport: Initial Findings From the Train the Brain Project.

CONTEXT: A limiting factor for reducing anterior cruciate ligament injury risk is ensuring that the movement adaptions made during the prevention program transfer to sport-specific activity. Virtual reality provides a mechanism to assess transferability, and neuroimaging provides a means to assay the neural processes allowing for such skill transfer. OBJECTIVE: To determine the neural mechanisms for injury risk-reducing biomechanics transfer to sport after anterior cruciate ligament injury prevention training. DESIGN: Cohort study. SETTING: Research laboratory. PARTICIPANTS: Four healthy high school soccer athletes. INTERVENTIONS: Participants completed augmented neuromuscular training utilizing real-time visual feedback. An unloaded knee extension task and a loaded leg press task were completed with neuroimaging before and after training. A virtual reality soccer-specific landing task was also competed following training to assess transfer of movement mechanics. MAIN OUTCOME MEASURES: Landing mechanics during the virtual reality soccer task and blood oxygen level-dependent signal change during neuroimaging. RESULTS: Increased motor planning, sensory and visual region activity during unloaded knee extension and decreased motor cortex activity during loaded leg press were highly correlated with improvements in landing mechanics (decreased hip adduction and knee rotation). CONCLUSION: Changes in brain activity may underlie adaptation and transfer of injury risk-reducing movement mechanics to sport activity. Clinicians may be able to target these specific brain processes with adjunctive therapy to facilitate intervention improvements transferring to sport.

Structural Connectivity Related to Persistent Symptoms After Mild TBI in Adolescents and Response to Aerobic Training: Preliminary Investigation.

OBJECTIVE: To quantify structural connectivity abnormalities in adolescents with mild traumatic brain injury (mTBI) and to investigate connectivity changes following aerobic training using graph theory and diffusion tensor imaging tractography. SETTING: Outpatient research setting. PARTICIPANTS: Twenty-two children (age: 15.83 ± 1.77 years, 10 females) with 4 to 16 weeks of persistent symptoms after mTBI and a matched healthy comparison group. DESIGN: Randomized clinical trial of aerobic training and stretching comparison combined with case-control comparison. MAIN MEASURES: (1) Five global network measures: global efficiency (Eglob), mean local efficiency, modularity, normalized clustering coefficient (γ), normalized characteristic path length (λ), and small-worldness (σ). (2) The self-reported Post-Concussion Symptom Inventory score. RESULTS: At initial enrollment, adolescents with mTBI had significantly lower Eglob and higher γ, λ, and σ (all P < .05) than healthy peers. After the intervention, significantly increased Eglob and decreased λ (both P < .05) were found in the aerobic training group. Improvement in Post-Concussion Symptom Inventory scores was significantly correlated with the Eglob increase and λ decrease in the aerobic training and λ decrease in the stretching comparison group (all P < .05). CONCLUSION: This pilot study showed initial evidence that structural connectivity analysis was sensitive to brain network abnormalities and may serve as an imaging biomarker in children with persistent symptoms after mTBI.

Advanced Neuroimaging Techniques in Pediatric Hydrocephalus.

From the early days of pneumoencephalography and ventriculography to the emerging technology of magnetic resonance diffusion tensor imaging (DTI) of the present day, neuroimaging has always been a critical tool in the diagnosis and treatment of pediatric hydrocephalus. There is accumulating evidence from both human and animal research suggesting that one of the major pathophysiological mechanisms underlying poor outcomes in these children is damage to vulnerable white matter (WM) structures in the brain as a result of ventricular enlargement and increased intracranial pressure. However, a clear understanding of these WM abnormalities and their implications on neurobehavioral outcomes in these patients is not well understood. To this end, DTI has recently been studied to allow noninvasive quantification of these abnormalities. Our review discusses the evolution of neuroimaging in pediatric hydrocephalus and focuses on the use of advanced imaging techniques, such as DTI, which is supported by a growing body of literature as a promising noninvasive imaging tool in the diagnosis and long-term management of this patient population. We conclude with a brief discussion on emerging techniques and experimental imaging.

Functional and structural connectivity of the visual system in infants with perinatal brain injury.

BACKGROUND: Infants with perinatal brain injury are at risk of later visual problems. Advanced neuroimaging techniques show promise to detect functional and structural alterations of the visual system. We hypothesized that infants with perinatal brain injury would have less brain activation during a visual functional magnetic resonance imaging (fMRI) task and reduced task-based functional connectivity and structural connectivity as compared with healthy controls. METHODS: Ten infants with perinatal brain injury and 20 control infants underwent visual fMRI and diffusion tensor imaging (DTI) during natural sleep with no sedation. Activation maps, functional connectivity maps, and structural connectivity were analyzed and compared between the two groups. RESULTS: Most infants in both groups had negative activation in the visual cortex during the fMRI task. Infants with brain injury showed reduced activation in the occipital cortex, weaker connectivity between visual areas and other areas of the brain during the visual task, and reduced fractional anisotropy in white matter tracts projecting to visual regions, as compared with control infants. CONCLUSION: Infants with brain injury sustained in the perinatal period showed evidence of decreased brain activity and functional connectivity during a visual task and altered structural connectivity as compared with healthy term neonates.

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.

Analysis of head impact exposure and brain microstructure response in a season-long application of a jugular vein compression collar: a prospective, neuroimaging investigation in American football.

BACKGROUND: Historical approaches to protect the brain from outside the skull (eg, helmets and mouthpieces) have been ineffective in reducing internal injury to the brain that arises from energy absorption during sports-related collisions. We aimed to evaluate the effects of a neck collar, which applies gentle bilateral jugular vein compression, resulting in cerebral venous engorgement to reduce head impact energy absorption during collision. Specifically, we investigated the effect of collar wearing during head impact exposure on brain microstructure integrity following a competitive high school American football season. METHODS: A prospective longitudinal controlled trial was employed to evaluate the effects of collar wearing (n=32) relative to controls (CTRL; n=30) during one competitive football season (age: 17.04±0.67 years). Impact exposure was collected using helmet sensors and white matter (WM) integrity was quantified based on diffusion tensor imaging (DTI) serving as the primary outcome. RESULTS: With similar overall g-forces and total head impact exposure experienced in the two study groups during the season (p>0.05), significant preseason to postseason changes in mean diffusivity, axial diffusivity and radial diffusivity in the WM integrity were noted in the CTRL group (corrected p<0.05) but not in the collar group (p>0.05). The CTRL group demonstrated significantly larger preseason to postseason DTI change in multiple WM regions compared with the collar group (corrected p<0.05). DISCUSSION: Reduced WM diffusivity alteration was noted in participants wearing a neck collar after a season of competitive football. Collar wearing may have provided a protective effect against brain microstructural changes after repetitive head impacts. TRIAL REGISTRATION NUMBER: NCT02696200.

Structural connectivity abnormality in children with acute mild traumatic brain injury using graph theoretical analysis.

The traumatic biomechanical forces associated with mild traumatic brain injury (mTBI) typically impart diffuse, as opposed to focal, brain injury potentially disrupting the structural connectivity between neural networks. Graph theoretical analysis using diffusion tensor imaging was used to assess injury-related differences in structural connectivity between 23 children (age 11-16 years) with mTBI and 20 age-matched children with isolated orthopedic injuries (OI) scanned within 96 h postinjury. The distribution of hub regions and the associations between alterations in regional network measures and symptom burden, as assessed by the postconcussion symptom scale score (PCSS), were also examined. In comparison to the OI group, the mTBI group was found to have significantly higher small-worldness (P < 0.0001), higher normalized clustering coefficients (P < 0.0001), higher normalized characteristic path length (P = 0.007), higher modularity (P = 0.0005), and lower global efficiency (P < 0.0001). A series of hub regions in the mTBI group were found to have significant alterations in regional network measures including nodal degree, nodal clustering coefficient, and nodal between-ness centrality. Correlation analysis showed that PCSS total score acquired at the time of imaging was significantly associated with the nodal degree of two hubs, the superior frontal gyrus at orbital section and the middle frontal gyrus. These findings provide new evidence of acute white matter alteration at both global and regional network level following mTBI in children furthering our understanding of underlying mechanisms of acute neurological insult associated with mTBI.