Maya Weinstein

Abnormal White Matter Integrity in Young Children with Autism

This study investigated white matter integrity in young children with autism using diffusion tensor imaging (DTI). Twenty‐two children with autism, mean age 3:2 years, and 32 controls, mean age 3:4 years, participated in the study. Tract‐based spatial statistics (TBSS) revealed white matter abnormalities in several distinct clusters within the genu and body of the corpus callosum (CC), left superior longitudinal fasciculus (SLF) and right and left cingulum (Cg). TBSS–VOIs analysis was performed in the clusters where differences in fractional anisotropy (FA) were detected to investigate the relationship between changes in FA and diffusivity indices. In all VOIs, increase in FA was caused by a decrease in radial diffusivity (Dr), while no changes in axial diffusivity (Da) or mean diffusivity (MD) were observed. Tractography analysis was applied to further study the CC, SLF, and Cg. Witelson parcellation scheme was used for the CC. Significant increase in FA was seen in children with autism in the mid‐body of the CC as well as in the left Cg. It is suggested that such abnormal white matter integrity in young children with autism may adversely affect connectivity between different brain regions and may be linked to some of the behavioral impairments apparent in autism. Hum Brain Mapp, 2011.

A multi-site study of functional outcomes following a themed approach to hand-arm bimanual intensive therapy for children with hemiplegia.

This study investigated the effects of a theme‐based (‘magic’) variation of the hand–arm bimanual intensive therapy programme, in two different countries, in improving activity performance for children with hemiplegia, including those with severe movement restrictions.

MRI-based radiologic scoring system for extent of brain injury in children with hemiplegia.

BACKGROUND AND PURPOSE: Brain MR imaging is recommended in children with cerebral palsy. Descriptions of MR imaging findings lack uniformity, due to the absence of a validated quantitative approach. We developed a quantitative scoring method for brain injury based on anatomic MR imaging and examined the reliability and validity in correlation to motor function in children with hemiplegia. MATERIALS AND METHODS: Twenty-seven children with hemiplegia underwent MR imaging (T1, T2-weighted sequences, DTI) and motor assessment (Manual Ability Classification System, Gross Motor Functional Classification System, Assisting Hand Assessment, Jebsen Taylor Test of Hand Function, and Childrens Hand Experience Questionnaire). A scoring system devised in our center was applied to all scans. Radiologic score covered 4 domains: number of affected lobes, volume and type of white matter injury, extent of gray matter damage, and major white matter tract injury. Inter- and intrarater reliability was evaluated and the relationship between radiologic score and motor assessments determined. RESULTS: Mean total radiologic score was 11.3 ± 4.5 (range 4–18). Good inter- (ρ = 0.909, P < .001) and intrarater (ρ = 0.926, P = < .001) reliability was demonstrated. Radiologic score correlated significantly with manual ability classification systems (ρ = 0.708, P < .001), and with motor assessments (assisting hand assessment [ρ = −0.753, P < .001]; Jebsen Taylor test of hand function [ρ = 0. 766, P < .001]; childrens hand experience questionnaire [ρ = −0. 716, P < .001]), as well as with DTI parameters. CONCLUSIONS: We present a novel MR imaging–based scoring system that demonstrated high inter- and intrarater reliability and significant associations with manual ability classification systems and motor evaluations. This score provides a standardized radiologic assessment of brain injury extent in hemiplegic patients with predominantly unilateral injury, allowing comparison between groups, and providing an additional tool for counseling families.

Neonatal neuropsychology: Emerging relations of neonatal sensory-motor responses to white matter integrity

The neonatal period is considered to be essential for neurodevelopment and wellbeing throughout the life span, yet little is known about brain-behavior relationships in the neonatal period. The aim of this study was to evaluate the association between neonatal sensory-motor regulation and white-matter (WM) integrity of major fiber tracts in the neonatal period. We hypothesized that WM integrity of sensory-motor systems would predict neurobehavioral maturation during the first month of life. Forty-nine premature neonates underwent magnetic-resonance-imaging at term. Diffusion-tensor-imaging analysis was performed in major WM tracts along with repeated neonatal neurobehavioral evaluations assessing sensory reactivity and motor regulation. Difficulties in one or more behavioral sub-category, mostly in auditory and visual attention, hypotonicity and jitteriness, were documented in 78.3% infants at term. Sixty-six percent of infants experienced difficulties, mostly in auditory attention, head-neck control, hypotonicity and motor asymmetry, at 44 weeks. Attention difficulties were associated with reduced integrity of cerebral and superior cerebellar peduncles; while tonicity was associated with reduced integrity of the corpus-callosum and inferior-posterior tracts. Overall, results showed that early maturing tracts were related with the degree of typicality of sensory reactivity status while late maturing tracts were related with the degree of typicality of tonic regulation. WM integrity and maturation factors explained 40.2% of the variance in neurobehavior at 44 weeks. This study suggests that in preterm neonates, deviant sensory-motor reactivity can be detected very early in development in manners that are related to lower integrity/maturational level of early and late maturing fiber tracts.

Cortical reorganization following injury early in life

The brain has a remarkable capacity for reorganization following injury, especially during the first years of life. Knowledge of structural reorganization and its consequences following perinatal injury is sparse. Here we studied changes in brain tissue volume, morphology, perfusion, and integrity in children with hemiplegia compared to typically developing children, using MRI. Children with hemiplegia demonstrated reduced total cerebral volume, with increased cerebrospinal fluid (CSF) and reduced total white matter volumes, with no differences in total gray matter volume, compared to typically developing children. An increase in cortical thickness at the hemisphere contralateral to the lesion (CLH) was detected in motor and language areas, which may reflect compensation for the gray matter loss in the lesion area or retention of ipsilateral pathways. In addition, reduced cortical thickness, perfusion, and surface area were detected in limbic areas. Increased CSF volume and precentral cortical thickness and reduced white matter volume were correlated with worse motor performance. Brain reorganization of the gray matter within the CLH, while not necessarily indicating better outcome, is suggested as a response to neuronal deficits following injury early in life.

Brain Plasticity following Intensive Bimanual Therapy in Children with Hemiparesis: Preliminary Evidence

Neuroplasticity studies examining children with hemiparesis (CH) have focused predominantly on unilateral interventions. CH also have bimanual coordination impairments with bimanual interventions showing benefits. We explored neuroplasticity following hand-arm bimanual intensive therapy (HABIT) of 60 hours in twelve CH (6 females, mean age 11 ± 3.6 y). Serial behavioral evaluations and MR imaging including diffusion tensor (DTI) and functional (fMRI) imaging were performed before, immediately after, and at 6-week follow-up. Manual skills were assessed repeatedly with the Assisting Hand Assessment, Childrens Hand Experience Questionnaire, and Jebsen-Taylor Test of Hand Function. Beta values, indicating the level of activation, and lateralization index (LI), indicating the pattern of brain activation, were computed from fMRI. White matter integrity of major fibers was assessed using DTI. 11/12 children showed improvement after intervention in at least one measure, with 8/12 improving on two or more tests. Changes were retained in 6/8 children at follow-up. Beta activation in the affected hemisphere increased at follow-up, and LI increased both after intervention and at follow-up. Correlations between LI and motor function emerged after intervention. Increased white matter integrity was detected in the corpus callosum and corticospinal tract after intervention in about half of the participants. Results provide first evidence for neuroplasticity changes following bimanual intervention in CH.

Isolated mild white matter signal changes in preterm infants: A regional approach for comparison of cranial ultrasound and MRI findings

Objective:To compare echogenicity detected using cranial ultrasound (cUS) and diffuse excessive high signal intensity (DEHSI) detected using magnetic resonance imaging (MRI) by identical region-based scoring criteria in preterm infants. To explore the association between these white matter (WM) signal changes with early neurobehavior.Study Design:Forty-nine pre-selected premature infants with only echogenicity on a first routine cUS1 underwent MRI and a repeated cUS2 at term equivalent age. Echogenicity and DEHSI were graded in various brain areas and diffusivity values were calculated. Neurobehavior was assessed using the Rapid Neonatal Neurobehavioral Assessment Procedure.Result:WM signal changes were significantly higher on cUS1 than cUS2; and higher in MRI than cUS2 in posterior regions. Infants with DEHSI demonstrated reduced tissue integrity. Imaging findings were not correlated with early neurobehavior.Conclusion:Echogenicity and DEHSI likely represent the same phenomenon. Reduction of over-interpretation of WM signal changes may help define criteria for the judicious use of imaging in routine follow-up of premature infants.

Imaging Predictors of Improvement From a Motor Learning–Based Intervention for Children With Unilateral Cerebral Palsy

Background. Motor-learning interventions may improve hand function in children with unilateral cerebral palsy (UCP) but with inconsistent outcomes across participants. Objective. To examine if pre-intervention brain imaging predicts benefit from bimanual intervention. Method. Twenty children with UCP with Manual Ability Classification System levels I to III, aged 7-16 years, participated in an intensive bimanual intervention. Assessments included the Assisting Hand Assessment (AHA), Jebsen Taylor Test of Hand Function (JTTHF) and Children’s Hand Experience Questionnaire (CHEQ) at baseline (T1), completion (T2) and 8-10 weeks post-intervention (T3). Imaging at baseline included conventional structural (radiological score), functional (fMRI) and diffusion tensor imaging (DTI). Results. Improvements were seen across assessments; AHA (P = 0.04), JTTHF (P < .001) and CHEQ (P < 0.001). Radiological score significantly correlated with improvement at T2; AHA (r = .475) and CHEQ (r = .632), but negatively with improvement on unimanual measures at T3 (JTTFH r = −.514). fMRI showed negative correlations between contralesional brain activation when moving the affected hand and AHA improvements (T2: r = −.562, T3: r = −0.479). Fractional Anisotropy in the affected posterior limb of the internal capsule correlated negatively with increased bimanual use on CHEQ at T2 (r = −547) and AHA at T3 (r = −.656). Conclusions. Children with greater structural, functional and connective brain damage showed enhanced responses to bimanual intervention. Baseline imaging may identify parameters predicting response to intervention in children with UCP.

The motor and visual networks in preterm infants: An fMRI and DTI study.

Knowledge regarding the association between functional connectivity and white-matter (WM) maturation of motor and visual networks in preterm infants at term equivalent age (TEA) and their association with behavioral outcome is currently limited. Thirty-two preterm infants born <34 weeks gestational-age without major brain abnormalities were included in this study, underwent resting-state fMRI at TEA. Thirteen infants also underwent diffusion tensor imaging (DTI). Neurobehavioral assessments were performed at one and two years corrected age using the Griffiths Mental Developmental Scales. Functional connectivity between homolog motor and visual regions were detected, which may reflect that a level of organization in these domains is present already at TEA. DTI parameters of WM tracts at TEA demonstrated spatial-temporal variability, with the splenium of the corpus-callosum (CC) found to be the most mature fiber bundle. Correlations between DTI parameters, functional connectivity and behavioral outcome were detected, yet did not show the same pattern of diffusivity changes in the different networks. Visual functional connectivity was negatively correlated with radial-diffusivity (RD) in the optic radiation, while motor functional connectivity was positively correlated with RD in the splenium. In addition, axial-diffusivity (AD) and RD in the genu and midbody of the CC were positively correlated with neurobehavioral outcome at one and 2 years of age. This study highlights the importance of understanding the spatial-temporal changes occurring during this sensitive period of development and the potential effect of extrauterine exposure on the microstructural changes as measured by DTI; their correlation with functional connectivity; and their long term relationship with neuro-behavioral development.