Thalamic connectivity topography in newborns with spina bifida: association with neurological functional level but not developmental outcome at 2 years.

Spina bifida affects spinal cord and cerebral development, leading to motor and cognitive delay. We investigated whether there are associations between thalamocortical connectivity topography, neurological function, and developmental outcomes in open spina bifida. Diffusion tensor MRI was used to assess thalamocortical connectivity in 44 newborns with open spina bifida who underwent prenatal surgical repair. We quantified the volume of clusters formed based on the strongest probabilistic connectivity to the frontal, parietal, and temporal cortex. Developmental outcomes were assessed using the Bayley III Scales, while the functional level of the lesion was assessed by neurological examination at 2 years of age. Higher functional level was associated with smaller thalamo-parietal, while lower functional level was associated with smaller thalamo-temporal connectivity clusters (Bonferroni-corrected P < 0.05). Lower functional levels were associated with weaker thalamic temporal connectivity, particularly in the ventrolateral and ventral anterior nuclei. No associations were found between thalamocortical connectivity and developmental outcomes. Our findings suggest that altered thalamocortical circuitry development in open spina bifida may contribute to impaired lower extremity function, impacting motor function and independent ambulation. We hypothesize that the neurologic function might not merely be caused by the spinal cord lesion, but further impacted by the disruption of cerebral neuronal circuitry.

Creative Music Therapy and Neurodevelopmental Outcomes in Pre-term Infants at 2 Years: A Randomized Controlled Pilot Trial.

Impaired neurodevelopment is increasingly recognized as a major health issue in children born prematurely. Creative music therapy (CMT) intends to prevent and or reduce neurobehavioral deficits in pre-term infants using musical stimulation and socio-emotional co-regulation. We conducted a randomized, clinical pilot CMT trial to test feasibility and to examine long-term neurodevelopmental outcomes in pre-term infants (NCT02434224: https://clinicaltrials.gov/ct2/show/NCT02434224). Eighty-two pre-term infants were randomized either to CMT or standard care. A specially trained music therapist provided family-integrating CMT via infant-directed singing during hospitalization. Fifty-six infants underwent follow-up at 2 years of corrected age. No significant beneficial nor adverse effects of CMT were identified in routine clinical neurodevelopmental measures (Bayley-III Scales of Infant and Toddler Development and the standardized neurological examination). Longer term follow-up (5 years) and larger future studies are recommended to elucidate possible long-term effects of music in relation to more sensitive outcomes including executive function, detailed language processing and social-emotional development.

Mental development is associated with cortical connectivity of the ventral and nonspecific thalamus of preterm newborns.

INTRODUCTION: The thalamus is a key hub for regulating cortical connectivity. Dysmaturation of thalamocortical networks that accompany white matter injury has been hypothesized as neuroanatomical correlate of late life neurocognitive impairment following preterm birth. Our objective was to find a link between thalamocortical connectivity measures at term equivalent age and two-year neurodevelopmental outcome in preterm infants. METHODS: Diffusion tensor MRI data of 58 preterm infants (postmenstrual age at birth, mean (SD), 29.71 (1.47) weeks) were used in the study. We utilized probabilistic diffusion tractography to trace connections between the cortex and thalami. Possible associations between connectivity strength, the length of the probabilistic fiber pathways, and developmental scores (Bayley Scales of Infant Development, Second Edition) were analyzed using multivariate linear regression models. RESULTS: We found strong correlation between mental developmental index and two complementary measures of thalamocortical networks: Connectivity strength projected to a cortical skeleton and pathway length emerging from thalamic voxels (partial correlation, R = .552 and R = .535, respectively, threshold-free cluster enhancement, corrected p-value < .05), while psychomotor development was not associated with thalamocortical connectivity. Post hoc stepwise linear regression analysis revealed that parental socioeconomic scale, postmenstrual age, and the duration of mechanical ventilation at the intensive care unit contribute to the variability of outcome. CONCLUSIONS: Our findings independently validated previous observations in preterm infants, providing additional evidence injury or dysmaturation of tracts emerging from ventral-specific and various nonspecific thalamus projecting to late-maturing cortical regions are predictive of mental, but not psychomotor developmental outcomes.

Multimodal assessment shows misalignment of structural and functional thalamocortical connectivity in children and adolescents born very preterm.

Thalamocortical connections are altered following very preterm birth but it is unknown whether structural and functional alterations are linked and how they contribute to neurodevelopmental deficits. We used a multimodal approach in 27 very preterm and 35 term-born children and adolescents aged 10-16 years: Structural thalamocortical connectivity was quantified with two measures derived from probabilistic tractography of diffusion tensor data, namely the volume of thalamic segments with cortical connections and mean fractional anisotropy (FA) within the respective segments. High-density sleep EEG was recorded and sleep spindles were identified at each electrode. Sleep spindle density and integrated spindle activity (ISA) were calculated to quantify functional thalamocortical connectivity. In term-born participants, the volume of the global thalamic segment with cortical connections was strongly related to sleep spindles across the entire head (mean r â€‹= â€‹.53 â€‹± .10; range â€‹= â€‹0.35 to 0.78). Regionally, the volume of the thalamic segment connecting to frontal brain regions correlated with sleep spindle density in two clusters of electrodes over fronto-temporal brain regions (.42 â€‹± .06; 0.35 to 0.51 and 0.43 â€‹± .08; 0.35 to 0.62) and the volume of the thalamic segment connecting to parietal brain regions correlated with sleep spindle density over parietal brain regions (mean r â€‹= â€‹.43 â€‹± .07; 0.35 to 0.61). In very preterm participants, the volume of the thalamic segments was not associated with sleep spindles. In the very preterm group, mean FA within the global thalamic segment was negatively correlated with ISA over a cluster of frontal and temporo-occipital brain regions (mean r â€‹= â€‹-.53 â€‹± .07; -.41 to -.72). No association between mean FA and ISA was found in the term-born group. With this multimodal study protocol, we identified a potential misalignment between structural and functional thalamocortical connectivity in children and adolescents born very preterm. Eventually, this may shed further light on the neuronal mechanisms underlying neurodevelopmental sequelae of preterm birth.

Creative music therapy to promote brain function and brain structure in preterm infants: A randomized controlled pilot study.

Cognitive and neurobehavioral problems are among the most severe adverse outcomes in very preterm infants. Such neurodevelopmental impairments may be mitigated through nonpharmacological interventions such as creative music therapy (CMT), an interactive, resource- and needs-oriented approach that provides individual social contact and musical stimulation. The aim was to test the feasibility of a study investigating the role of CMT and to measure the short- and medium-term effects of CMT on structural and functional brain connectivity with MRI. In this randomized, controlled clinical pilot feasibility trial, 82 infants were randomized to either CMT or standard care. A specially trained music therapist provided CMT via infant-directed humming and singing in lullaby style. To test the short-term effects of CMT on brain structure and function, diffusion tensor imaging data and resting-state functional imaging data were acquired. Clinical feasibility was achieved despite moderate parental refusal mainly in the control group after randomization. 40 infants remained as final cohort for the MRI analysis. Structural brain connectivity appears to be moderately affected by CMT, structural connectomic analysis revealed increased integration in the posterior cingulate cortex only. Lagged resting-state MRI analysis showed lower thalamocortical processing delay, stronger functional networks, and higher functional integration in predominantly left prefrontal, supplementary motor, and inferior temporal brain regions in infants treated with CMT. This trial provides unique evidence that CMT has beneficial effects on functional brain activity and connectivity in networks underlying higher-order cognitive, socio-emotional, and motor functions in preterm infants. Our results indicate the potential of CMT to improve long-term neurodevelopmental outcomes in children born very preterm.

Creative music therapy to promote brain structure, function, and neurobehavioral outcomes in preterm infants: a randomized controlled pilot trial protocol.

BACKGROUND: Preterm birth is associated with increased risk of neurological impairment and deficits in cognition, motor function, and behavioral problems. Limited studies indicate that multi-sensory experiences support brain development in preterm infants. Music appears to promote neurobiological processes and neuronal learning in the human brain. Creative music therapy (CMT) is an individualized, interactive therapeutic approach based on the theory and methods of Nordoff and Robbins. CMT may promote brain development in preterm infants via concurrent interaction and meaningful auditory stimulation. We hypothesize that preterm infants who receive creative music therapy during neonatal intensive care admission will have developmental benefits short- and long-term brain function. METHODS/DESIGN: A prospective, randomized controlled single-center pilot trial involving 60 clinically stable preterm infants under 32 weeks of gestational age is conducted in preparation for a multi-center trial. Thirty infants each are randomized to either standard neonatal intensive care or standard care with CMT. Music therapy intervention is approximately 20 min in duration three times per week. A trained music therapist sings for the infants in lullaby style, individually entrained and adjusted to the infant's rhythm and affect. Primary objectives of this study are feasibility of protocol implementation and investigating the potential mechanism of efficacy for this new intervention. To examine the effect of this new intervention, non-invasive, quantitative magnetic resonance imaging (MRI) methods at corrected age and standardized neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development third edition at a corrected age of 24 months and Kaufman Assessment Battery for Children at 5 years will be performed. All assessments will be performed and analyzed by blinded experts. DISCUSSION: To our knowledge, this is the first randomized controlled clinical trial to systematically examine possible effects of creative music therapy on short- and long-term brain development in preterm infants. This project lies at the interface of music therapy, neuroscience, and medical imaging. New insights into the potential role and impact of music on brain function and development may be elucidated. If such a low-cost, low-risk intervention is demonstrated in a future multi-center trial to be effective in supporting brain development in preterm neonates, findings could have broad clinical implications for this vulnerable patient population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02434224.

Regional neonatal brain absolute thermometry by 1H MRS.

Therapeutic hypothermia is standard care for infants with moderate to severe encephalopathy. (1) H MRS thermometry (MRSt) measures regional brain absolute temperature using the temperature-dependent water chemical shift. This study evaluates the clinical feasibility of MRSt in human neonates, and correlates white matter (WM) and thalamus (Thal) MRSt with conventional rectal temperature (Trectal ) measurement. Fifty-six infants born at term underwent perinatal MRSt for suspected hypoxic-ischaemic brain injury and 33 infants born preterm had MRSt at a term-equivalent age; 56 of the 89 had Trectal measured after MRSt of either a Thal or posterior WM voxel, or both. MRSt used point-resolved spectroscopy (no water suppression; TR = 1370 ms; TE = 288 ms; 1.5 × 1.5 × 1.5 cm(3) Thal and 1.1 × 1.3 × 1.4 cm(3) WM voxels). Time domain data were phase and frequency corrected before summation and motion-corrupted data were excluded from further analysis using simple criteria [preprocessing + quality assurance (QA)]. Two published water temperature-dependence calibrations [both using cerebral creatine (Cr), choline (Cho) and N-acetylaspartate (Naa) as independent reference peaks] were compared. The temperature measurements derived from Cr, Cho and Naa were combined to give a single amplitude-weighted combination temperature (TAWC ). WM and Thal TAWC correlated linearly with Trectal (Thal slope, 0.82 ± 0.04, R(2) = 0.85, p < 0.05; WM slope, 0.95 ± 0.04, R(2) = 0.78, p < 0.05). Preprocessing + QA improved the correlation between WM TAWC and Trectal (R(2) increased from 0.27 to 0.78, p < 0.001). Both calibration datasets showed specific inconsistencies between the temperatures calculated using Cr, Cho and Naa reference peaks when applied to this neonatal dataset. Neonatal MRSt is clinically feasible. Preprocessing + QA improved MRSt reliability in WM. The consideration of MRSt calibration internal biases is necessary before combining MRSt temperatures from multiple reference peaks to obtain TAWC.