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Introduction: Improvements in obstetric/neonatal care have increased the survival rates of extremely-preterm-born (EP), though followed by an increased number, and degrees, of white matter injury (WMI), and long-lasting neurodevelopmental impairments. Study aim: to investigate consequences of EP birth on the evolving white matter microstructure and myelination; and its causative role on acquired IQ and sensory-motor functions.

Participants and methods: Two MRI methods (3T; DTI and SyMRI) used to calculate white matter properties and associations with IQ and sensory-motor functions in children born FT and EP at 12-y. In total N = 57 children; 32 FT (GA 38-42), and 25 EP (GA 22- <27) successfully performed MRI and administered WISC-V and Beery visual-motor integration (VMI) test. DTI used for analyzing fractional anisotropy (FA), mean diffusivity (MD), axial- (AD) and radial diffusivity (RD). SyMRI (T1-T2-R1-R2 and PD) for analyzing myelin segmentation, white-matter (WM), gray-matter (GM), cerebrospinal fluid (CSF), and brain parenchyma volume (BPV).

Results: Children born EP had significant smaller total brain (BPV), less GM, WM and more CSF/ICV compared to FT born. GA correlated positively with brain volumes, myelin, and with IQ and Beery-WMI. For EPs myelin correlated positively with GA, WISC-V and Beery-VMI. EPs had significant higher RD and AD compared to FT, no significant FA difference found. Within EP-group, myelin content correlated positively with FA and negatively with RD and AD.

Conclusion: These findings suggest that EP births is associated with high-risk for long-lasting, globally compromised white matter myelination and microstructural organization which causes adverse cognitive and sensory-motor functions.

Introduction: Knowledge is lacking concerning long-term influences of preterm birth on action-cognition integrations related to corpus callosum (CC) maturation/myelination. Here, we investigate long-term-effects of preterm-birth on CC microstructures/organization in relation to cognition and functional-laterality.

Patients and methods: The sample included 82 children, 41 term-born (M-age=8.1y), and 41 preterm-born (M-age=8.2y); subdivided into V-PT, (GA=25–32w, N=23), and M-PT, (GA=33–35w, N=18), without major brain-deficits. DTI performed in 3T-MRI-scanners, generated maps of CC Genu, Truncus, Splenium (FA, MD, AD, RD-values). Results from WISC-IV (verbal-comprehension-VCI, perceptual-reasoning-PRI, working-memory-WM, processing-speed-PS, FSIQ), and Laterality-index (hand-, foot-, eye-preference) were analyzed related to DTI-outcomes.

Results: Significant group difference found regarding CC-FA-values (F(2,79)=5,3527, p=.006), post-hoc-test showed that VPT differed from term (p=.015) and MPT-born (p=.016), by lower FA-Genu, Truncus, Splenium. This pattern also found for MD, RD, and AD-values. Positive-correlations (p<.01) found between GA and all CC-FA-values, and negatively for all MD, RD and AD-Splenium. VPT-born showed lower (p=.005) FSIQ (M=93) than term (M=103). Correlations (p<.05) found between WM and CC-FA-values in Genu for VPT-born, and between CC-FA-values in Genu, Truncus and PRI-index (p<.01) for term-born. VPT-born showed lower Hand- and overall-laterality-index than term and MPT, and no significant correlations between laterality-index and CC-values. Term and MPT-children showed positive correlations (p<.01) between decreasing overall-laterality-index and FA-values, and negative for MD-Splenum, RD-Splenium and RD-Truncus. 

Conclusion: DTI revealed evidence for long-term impact of very-premature birth on CC related to atypical hemispheric maturation and behavioral integrations compared to term-born controls. The findings highlight importance of including functional-laterality to models investigating brain white-matter-microstructures.

INTRODUCTION/BACKGROUND: Recent studies have found that a reduced growth of the cerebellum is associated with poorer scores on both general intelligence tests and motor balance tests (Matthews et al., 2018) in children born preterm (PT), and that lower test scores may be persistent in adolescents born very PT (Allin et al., 2001). Notably, even low-risk children born PT at 9-years of age have been reported displaying regional brain volume reduction in the cerebellum (Arhan et al., 2017). So far, however, few studies have been conducted on cerebellar volumes and the role of its myelinated content, and if/how cerebellar myelination is associated with cognitive and kinematic outcome performance in children born PT.

To this end, the present study aim was to investigate whether cerebellar volumes were associated with gestational age (GA) and/or birth weight (BW) in a sample of children born PT (without known focal lesions) compared to controls (term born). We also wished to explore whether the cerebellum volumetric analyses, targeting the amount of myelinated content, would be linked to the children’s cognitive and motor performance. 

PATIENTS AND METHODS: The sample consisted of 59 children investigated at early school-age (M = 8.17 years), 27 born PT (divided into moderately PT, MPT, and very PT, VPT) and 32 born full-term (FT). Brain scans were conducted by a 3.0-Tesla MRI scanner and Synthetic MRI (SyMRI) was used to investigate brain and cerebellar volumes and additionally, the amount of myelin content. Cognitive performance was assessed by the Wechsler Intelligence Scale for Children, 4th Edition (WISC-IV), and goal-directed upper-limb movement kinematics were recorded by a 6-camera, optoelectronic 3D registrations system (240Hz). 

RESULTS: The results displayed reduced volumes of the cerebellum for children born VPT (see Table 1), and  smaller volumes were significantly associated with lower GA and BW. Children born VPT showed significantly lower full scale intelligence quotient (FSIQ) scores than children born MPT and FT. Overall, reduced myelinated content in the cerebellum was also significantly associated with lower FSIQ scores (see Fig.1). The children born VPT further displayed significantly poorer upper-limb kinematics than the other groups. However, no evident overall (independent of GA at birth) correlation was found between reduced volumes of the cerebellum and the kinematic performance. 

CONCLUSIONS: A very preterm birth (< 32 weeks’ of gestation) increases the risk for long-term effects on cerebellar volumes, including less myelin content, and poorer cognitive and motor performance. The findings emphasize the importance of myelinated content in cerebellum and its role for cognitive function and upper-limb movement performance in children born very preterm. These findings merit for further longitudinal studies including bigger samples of both preterm and term born infants and children.

Keywords: preterm, children, cerebellum, brain volumes, myelin, cognitive functioning, motor functioning

References:

Matthews et al., Longitudinal preterm cerebellar volume: perinatal and neurodevelopmental outcome associations. The Cerebellum, 2018, 17(5), 610-627.

Allin et al., Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term. Brain, 2001, 124(1), 60-66.

Arhan et al., Regional brain volume reduction and cognitive outcomes in preterm children at low risk at 9 years of age. Child's Nervous System, 2017, 33, 8, 1317–1326.

OBJECTIVE: To determine whether neurofilament light chain protein in CSF (cNfL), a sensitive biomarker of neuroaxonal damage, reflects disease severity or can predict survival in Parkinson disease (PD).

METHODS: We investigated whether disease severity, phenotype, or survival in patients with new-onset PD correlates with cNfL concentrations around the time of diagnosis in the population-based New Parkinsonism in Umeå (NYPUM) study cohort (n = 99). A second, larger new-onset PD cohort (n = 194) was used for independent validation. Association of brain pathology with the cNfL concentration was examined with striatal dopamine transporter imaging and repeated diffusion tensor imaging at baseline and 1 and 3 years.

RESULTS: Higher cNfL in the early phase of PD was associated with greater severity of all cardinal motor symptoms except tremor in both cohorts and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death during follow-up. After adjustment for age and sex, higher cNfL correlated with striatal dopamine transporter uptake deficits and lower fractional anisotropy in diffusion tensor imaging of several axonal tracts.

CONCLUSIONS: cNfL shows usefulness as a biomarker of disease severity and to predict survival in PD. The present results indicate that the cNfL concentration reflects the intensity of the neurodegenerative process, which could be important in future clinical trials.

CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with PD, cNfL concentrations are associated with more severe disease and shorter survival.

Introduction: Long-term outcomes linked to preterm (PT) births have generally found an increased amount of neuromotor-developmental delays and/or disabilities. Few studies have addressed how upper-limb kinematics associates with brain volumes and myelination. This study aimed to investigate such possible relationships within children born PT compared with term-born controls at early school age, in relation to gestational age (GA) and birth-weight (BW).

Material and methods: This sub-study, part of a multidisciplinary project exploring long-term effects of PT births, included 27 children (Mean age= 8.2y) born PT (Mean GA= 32-weeks, range 22-35), and 33 age-matched born term. Kinematics of task-specific head and bi-/uni-manual upper-limb-movements was measured by a 3D-registration system (ProReflex). Brain volumes and myelin content were investigated by a 3-Tesla, magnetic resonance imaging (MRI)-scanner with a 7-min Synthetic MRI (SyMRI) acquisition-sequence.

Results: Significantly (p < .05) less efficient upper-limb kinematics with more segmented and longer movement paths was found in PT-born compared with term-born, particularly evident for those extremely-/very PT-born (<32 GA). Smaller total brain volumes and regional white-matter reduction with less myelin were significantly correlated with more segmented and longer arm- and head-trajectories, and with lower GA and BW.

Discussion-conclusion: The present findings show that an extremely- and very-PT-birth may cause long-term effects on neuromotor-mechanisms involved in goal-directed movements and that these effects are associated with generally delayed brain development and myelination. Additionally, SyMRI stands out as a suitable and cost-effective method for longitudinal/follow-up of brain development and changes, reducing distress in children due to a decreased scan time.

Objectives: Rehabilitation of patients with chronic visuospatial neglect is underexplored, and little is known about neural mechanisms that can be exploited to promote recovery. In this study, we present data on resting-state functional connectivity within the dorsal attention network (DAN) in chronic neglect patients as they underwent training in a virtual reality (VR) environment that improved left-side awareness.

Methods: The study included 13 patients with visuospatial neglect persisting more than six months after a right-sided stroke. The patients underwent resting-state functional magnetic resonance imaging (fMRI). Scans were collected at baseline and after five weeks of intense training. We specifically examined resting-state functional connectivity within the DAN. In addition, using spatial concordance correlation, we compared changes in the spatial topology of the DAN with that of other networks.

Results: We found a longitudinal increase in interhemispheric functional connectivity between the right frontal eye field and the left intraparietal sulcus following training (before: 0.33 +/- 0.17 [mean +/- SD]; after: 0.45 +/- 0.13; P = 0.004). The spatial concordance analyses indicated that training influenced the DAN connectivity more than any of the other networks.

Conclusion: Intense VR training that improved left-sided awareness in chronic stroke patients also increased sporadic interhemispheric functional connectivity within the DAN. Specifically, a region responsible for saccadic eye movement to the left became more integrated with the left posterior parietal cortex. These results highlight a mechanism that should be exploited in the training of patients with chronic visuospatial neglect.

Introduction: Structural and functional alterations in white matter architecture are common described in children born preterm (PT) and associated to behavioral implications. Still, how critical gestational immaturity may associate with later myelination is less studied. This study aimed to explore the influence and associations between gestational age (GA) and birthweight (BW) in children born PT compared with fullterm (FT), on quantitative values of brain myelin and volumes.

Patients and methods: Participants included 60 children (mean age = 8.2 years) categorized based on GA (weeks); ranging from 25 - 35.4 in PTs (N=27); 38 - 41.9 in FTs (N=33). Volumetric brain measures were conducted by a 3.0-Tesla MRI-scanner and synthetic MRI (SyMRI) acquisition sequence, including synthesis of contrast weighted images. Automatic segmentation of total brain tissues (intracranial [ICV] and parenchymal [BPV] volume [ml]) generated gray-matter (GM), white-matter (WM), cerebrospinal fluid (CSF), and total myelin volume.

Result: Children born extremely PT (<27GW) displayed reductions of total BPV and WM compared to FTs, less myelinated content than very PT (VPT; < 32GW) and moderately PT (MPT; <36GW), and significant more CSF than FT-born. Significant positive correlation between respectively increasing GA (r= .48) and BW (r= .53) and amount of myelinated content were found for the PT-born.

Conclusion: Detection of diversity regarding myelination and brain-volumes and associations to risk factors related to gestational immaturity may be useful for increased understanding of long-term effects of degree of prematurity and allowing future investigations of how interventions effects brain myelination (and plasticity) in children born PT.

Objectives: A third of patients with stroke acquire spatial neglect associated with poor rehabilitation outcome. New effective rehabilitation interventions are needed. Scanning training combined with multisensory stimulation to enhance the rehabilitation effect is suggested. In accordance, we have designed a virtual-reality based scanning training that combines visual, audio and sensori-motor stimulation called RehAtt((R)). Effects were shown in behavioural tests and activity of daily living. Here, we use fMRI to evaluate the change in brain activity during Posners Cuing Task (attention task) after RehAtt((R)) intervention, in patients with chronic neglect.

Methods: Twelve patients (mean age=72.7years, SD=6.1) with chronic neglect (persistent symptoms >6months) performed the interventions 3 times/wk during 5weeks, in total 15hours. Training effects on brain activity were evaluated using fMRI task-evoked responses during the Posners cuing task before and after the intervention.

Results: Patients improved their performance in the Posner fMRI task. In addition, patients increased their task-evoked brain activity after the VR interventions in an extended network including pre-frontal and temporal cortex during attentional cueing, but showed no training effects during target presentations.

Conclusions: The current pilot study demonstrates that a novel multisensory VR intervention has the potential to benefit patients with chronic neglect in respect of behaviour and brain changes. Specifically, the fMRI results show that strategic processes (top-down control during attentional cuing) were enhanced by the intervention. The findings increase knowledge of the plasticity processes underlying positive rehabilitation effects from RehAtt((R)) in chronic neglect.

Altered white matter microstructure is commonly found in children born preterm (PT), especially those born at an extremely low gestational age (GA). These children also commonly show disturbed motor function. This study explores the relation between white matter alterations and upperlimb movement segmentation in 41 children born PT (19 girls), and 41 children born at term (18 girls) at 8 years. The PT group was subdivided into extremely PT (E-PT; GA = 25–27 weeks, N = 10), very PT (V-PT; GA = 28–32 weeks, N = 13), and moderately PT (M-PT; GA = 33–35 weeks, N = 18). Arm/hand preference (preferred/non-preferred) was determined through object interactions and the brain hemispheres were designated accordingly. White matter alterations were assessed using diffusion tensor imaging in nine areas, and movement segmentation of the body-parts head, shoulder, elbow, and wrist were registered during a unimanual goal-directed task. Increased movement segmentation was demonstrated consistently on the preferred side in the E-PT group compared with the term born group. Also compared with the term born peers, the E-PT group demonstrated reduced fractional anisotropy (FA) in the cerebral peduncle (targeting the corticospinal tract) in the hemisphere on the non-preferred side and in the splenium of corpus callosum. In contrast, in the anterior internal capsule on the preferred side, the E-PT group had increased FA. Lower FA in the cerebral peduncle, but higher FA in the anterior internal capsule, was associated with increased movement segmentation across body-parts in a contralateral manner. The results suggest that impaired development of sensorimotor tracts in E-PT children could explain a sub-optimal spatiotemporal organization of upper-limb movements.