Regional White Matter Microstructure Research Articles

Long-term brain structural and cognitive outcomes in a low-risk preterm-born sample

Prematurity has been related to altered brain structure and cognition, and so our aim was to describe them in the absence of major structural brain injury following low-risk preterm birth during adolescence and young adulthood. The sample consisted of 250 participants, 132 of whom were low-risk preterm (30–36 weeks’ gestational age) and 118 were full-term individuals (37–42 weeks’ gestational age), aged between 16 and 38 years old. All participants underwent an extensive neuropsychological assessment. T1- and diffusion-weighted MRI images of 33 low-risk preterm and 31 full-term young adults (20–32 years old) were analyzed. No differences were found in terms of general cognitive functioning score or current socioeconomic status; however, the low-risk preterm group obtained lower scores in phonetic and semantic fluencies, and theory of mind. Significant reductions were identified in the thalamus volume as well as thicker cortex in the inferior temporal gyrus in the low-risk preterm group. Low-risk preterm young adults evidenced greater regional AD and MD compared to the full-term sample; while low-risk preterm group showed lower mean NDI and ODI (FWE-corrected, p < 0.05). Being born preterm is associated with poorer performance in various cognitive domains (i.e., phonetic and semantic fluencies, and theory of mind) later in life, along with differences in normative structural brain development in inferior temporal gyrus and regional white matter microstructure.

Preoperative recovery sleep ameliorates postoperative cognitive dysfunction aggravated by sleep fragmentation in aged mice by enhancing EEG delta-wave activity and LFP theta oscillation in hippocampal CA1

Sleep fragmentation (SF) is a common sleep problem experienced during the perioperative period by older adults, and is associated with postoperative cognitive dysfunction (POCD). Increasing evidence indicates that delta-wave activity during non-rapid eye movement (NREM) sleep is involved in sleep-dependent memory consolidation and that hippocampal theta oscillations are related to spatial exploratory memory. Recovery sleep (RS), a self-regulated state of sleep homeostasis, enhances delta-wave power and memory performance in sleep-deprived older mice. However, it remains unclear whether RS therapy has a positive effect on cognitive changes following SF in older mouse models. Therefore, this study aimed to explore whether preoperative RS can alleviate cognitive deficits in aged mice with SF. A model of preoperative 24-h SF combined with exploratory laparotomy-induced POCD was established in 18-month-old mice. Aged mice were treated with preoperative 6-h RS following SF and postoperative 6-h RS following surgery, respectively. The changes in hippocampus-dependent cognitive function were investigated using behavioral tests, electroencephalography (EEG), local field potential (LFP), magnetic resonance imaging, and neuromorphology. Mice that underwent 24-h SF combined with surgery exhibited severe spatial memory impairment; impaired cognitive performance could be alleviated by preoperative RS treatment. In addition, preoperative RS increased NREM sleep; enhanced EEG delta-wave activity and LFP theta oscillation in the hippocampal CA1; and improved hippocampal perfusion, microstructural integrity, and neuronal damage. Taken together, these results provide evidence that preoperative RS may ameliorate the severity of POCD aggravated by SF by enhancing delta slow-wave activity and hippocampal theta oscillation, and by ameliorating the reduction in regional cerebral blood flow and white matter microstructure integrity in the hippocampus.

Reaction Time Variability in Children Is Specifically Associated With Attention Problems and Regional White Matter Microstructure

BackgroundIncreased intraindividual variability (IIV) in reaction times (RTs) has been suggested as a key cognitive and behavioral marker of attention problems, but findings for other dimensions of psychopathology are less consistent. Moreover, while studies have linked IIV to brain white matter microstructure, large studies testing the robustness of these associations are needed. MethodsWe used data from the Adolescent Brain Cognitive Development (ABCD) Study baseline assessment to test the associations between IIV and psychopathology (n = 8622, age = 8.9–11.1 years) and IIV and white matter microstructure (n = 7958, age = 8.9–11.1 years). IIV was investigated using an ex-Gaussian distribution analysis of RTs in correct response go trials in the stop signal task. Psychopathology was measured by the Child Behavior Checklist and a bifactor structural equation model was performed to extract a general p factor and specific factors reflecting internalizing, externalizing, and attention problems. To investigate white matter microstructure, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were examined in 23 atlas-based tracts. ResultsIncreased IIV in both short and long RTs was positively associated with the specific attention problems factor (Cohen’s d = 0.13 and d = 0.15, respectively). Increased IIV in long RTs was also positively associated with radial diffusivity in the left and right corticospinal tract (both tracts, d = 0.12). ConclusionsUsing a large sample and a data-driven dimensional approach to psychopathology, the results provide novel evidence for a small but specific association between IIV and attention problems in children and support previous findings on the relevance of white matter microstructure for IIV.

Structural and functional differences in the brains of patients with MCI with and without depressive symptoms and their relations with Alzheimer's disease: an MRI study.

The mild cognitive impairment (MCI) stage among elderly individuals is very complex, and the level of diagnostic accuracy is far from ideal. Some studies have tried to improve the 'MCI due to Alzheimer's disease (AD)' classification by further stratifying these patients into subgroups. Depression-related symptoms may play an important role in helping to better define the MCI stage in elderly individuals. In this work, we explored functional and structural differences in the brains of patients with nondepressed MCI (nDMCI) and patients with MCI with depressive symptoms (DMCI), and we examined how these groups relate to AD atrophy patterns and cognitive functioning. Sixty-five participants underwent MRI exams and were divided into four groups: cognitively normal, nDMCI, DMCI, and AD. We compared the regional brain volumes, cortical thickness, and white matter microstructure measures using diffusion tensor imaging among groups. Additionally, we evaluated changes in functional connectivity using fMRI data. In comparison to the nDMCI group, the DMCI patients had more pronounced atrophy in the hippocampus and amygdala. Additionally, DMCI patients had asymmetric damage in the limbic-frontal white matter connection. Furthermore, two medial posterior regions, the isthmus of cingulate gyrus and especially the lingual gyrus, had high importance in the structural and functional differentiation between the two groups. It is possible to differentiate nDMCI from DMCI patients using MRI techniques, which may contribute to a better characterization of subtypes of the MCI stage.

Lithium: more than a mood stabilizier

IntroductionBipolar disorder (BD) is characterized by episodic changes in affect, motivation, cognition and behavior. This severe mental disorder has a prevalence of at least 1% and a high heritability of 60%-80%. The pathophysiology is still poorly understood but evidence indicate that the disorder relates to disturbances in front-limbic networks relevant for emotion processing and regulation. New techniques have been used to study BD and showed aberrante white matter (WM) microstructure in the corpus callosum and from-limbic pathways. However, lithium, a mood stabilizier, it looks like has celular and neuromodulatory effects.ObjectivesThe authors elaborate a narrative literature review to identify the existing clinical evidence of lithium’s effect on the WM from BD patients.MethodsPubmed databased searched using the therms “bipolar disorder”, “white matter” and “lithium”.ResultsLithium is a bipolar medication that confers treatment and long-term prophylaxis and been reported as having neuroprotective effects.Studies that used new techniques such diffusion tensor imaging measures to assess white matter integrity reported a positive effect of lithium on the integrity of WM of BD patients and suggest that response to lithium treatment in BD patients is associated with normalization of WM microstructure in regions associated with emotion processing.ConclusionsLithium appears to positively influence the evolution of the white matter abnormalities described in BD patients however further investigation is required to strongly reinforce this potential and safety.DisclosureNo significant relationships.

Associations of body composition with regional brain volumes and white matter microstructure in very preterm infants

ObjectiveTo determine associations between body composition and concurrent measures of brain development including (1) Tissue-specific brain volumes and (2) White matter microstructure, among very preterm infants at term equivalent age.DesignProspective...

Cognitive Training in Parkinson\u2019s Disease Induces Local, Not Global, Changes in White Matter Microstructure

Previous studies showed that cognitive training can improve cognitive performance in various neurodegenerative diseases but little is known about the effects of cognitive training on the brain. Here, we investigated the effects of our cognitive training paradigm, COGTIPS, on regional white matter microstructure and structural network topology. We previously showed that COGTIPS has small, positive effects on processing speed. A subsample of 79 PD patients (N = 40 cognitive training group, N = 39 active control group) underwent multi-shell diffusion-weighted imaging pre- and post-intervention. Our pre-registered analysis plan (osf.io/cht6g) entailed investigating white matter microstructural integrity (e.g., fractional anisotropy) in five tracts of interest, including the anterior thalamic radiation (ATR), whole-brain tract-based spatial statistics (TBSS), and the topology of the structural network. Relative to the active control condition, cognitive training had no effect on topology of the structural network or whole-brain TBSS. Cognitive training did lead to a reduction in fractional anisotropy in the ATR (B [SE]: − 0.32 [0.12], P = 0.01). This reduction was associated with faster responses on the Tower of London task (r = 0.42, P = 0.007), but this just fell short of our statistical threshold (P < 0.006). Post hoc “fixel-based” analyses showed that this was not due to changes in fiber density and cross section. This suggests that the observed effect in the ATR is due to training-induced alterations in neighboring fibers running through the same voxels, such as intra-striatal and thalamo-striatal fibers. These results indicate that 8 weeks of cognitive training does not alter network topology, but has subtle local effects on structural connectivity.

Age-Related Variations in Regional White Matter Volumetry and Microstructure During the Post-adolescence Period: A Cross-Sectional Study of a Cohort of 1,713 University Students.

Human brain white matter undergoes a protracted maturation that continues well into adulthood. Recent advances in diffusion-weighted imaging (DWI) methods allow detailed characterizations of the microstructural architecture of white matter, and they are increasingly utilized to study white matter changes during development and aging. However, relatively little is known about the late maturational changes in the microstructural architecture of white matter during post-adolescence. Here we report on regional changes in white matter volume and microstructure in young adults undergoing university-level education. As part of the MRi-Share multi-modal brain MRI database, multi-shell, high angular resolution DWI data were acquired in a unique sample of 1,713 university students aged 18–26. We assessed the age and sex dependence of diffusion metrics derived from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) in the white matter regions as defined in the John Hopkins University (JHU) white matter labels atlas. We demonstrate that while regional white matter volume is relatively stable over the age range of our sample, the white matter microstructural properties show clear age-related variations. Globally, it is characterized by a robust increase in neurite density index (NDI), and to a lesser extent, orientation dispersion index (ODI). These changes are accompanied by a decrease in diffusivity. In contrast, there is minimal age-related variation in fractional anisotropy. There are regional variations in these microstructural changes: some tracts, most notably cingulum bundles, show a strong age-related increase in NDI coupled with decreases in radial and mean diffusivity, while others, mainly cortico-spinal projection tracts, primarily show an ODI increase and axial diffusivity decrease. These age-related variations are not different between males and females, but males show higher NDI and ODI and lower diffusivity than females across many tracts. These findings emphasize the complexity of changes in white matter structure occurring in this critical period of late maturation in early adulthood.

Association between breastfeeding during infancy and white matter microstructure in early childhood

IntroductionAssociations between breastfeeding and brain development, in the context of child, perinatal, and sociodemographic variables, remain unclear. This study investigated whether exclusive breastfeeding for the first 6 months and total duration of breastfeeding were associated with brain white matter microstructure in young children. MethodsThis study included 85 typically developing children (42 males) born to 83 mothers that were predominantly white, highly educated, and in high income households. Children underwent their first diffusion tensor imaging scan between ages 2.34 and 6.97 years; some children returned multiple times, providing a total of 331 datasets. Feeding information was collected from mothers at 3, 6, and 12 months postpartum and at their child's scan to calculate breastfeeding status at 6 months (exclusive or not) as well as total duration of any breastfeeding. Linear regression was used to investigate associations between breastfeeding exclusivity/duration and fractional anisotropy (FA) for the whole brain and 10 individual white matter tracts. ResultsBreastfeeding exclusivity and duration were associated with global and regional white matter microstructure, even after controlling for perinatal and sociodemographic factors. Greater exclusivity was associated with higher FA in females and lower FA in males. ConclusionsThese findings suggest white matter differences associated with breastfeeding that differ by sex. These may stem from different trajectories in white matter development between males and females in early childhood and suggest possible long-term white matter differences associated with breastfeeding.

No evidence for an effect of a working memory training program on white matter microstructure

Numerous studies demonstrate that working memory training benefits cognitive performance; however, such findings are controversial and the field is polarized. Despite a multitude of behavioural studies, investigation into the neurobiological mechanisms underlying working memory training remains limited. Diffusion tensor imaging (DTI) allows for the visualization of white matter structure and is a promising approach to identify neurobiological change associated with working memory training. In this study, 25 healthy community dwelling adults (age 18–40 years) underwent neuroimaging before and after completing a 6-week home- and web-based complex working memory training program. An active control group (n = 24) completed 6-weeks of processing speed training using the same computerized platform and imaging protocol. Voxel-wise statistical analysis of the DTI data was conducted with FSL's Tract-Based Spatial Statistics (TBSS) to assess change in several metrics over the course of the intervention. Additionally, averaged whole-brain values (i.e., throughout all cerebral white matter) for each DTI metric were examined via one-way analysis of covariance (ANCOVA). The participants' scores on the training tasks significantly improved post-training. The training was not associated with improved scores on non-trained cognitive measures. The working memory training also did not alter regional or global white matter microstructure, as measured by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Consistent with our previous published findings on brain activity and grey matter structure in the same study sample, the present study does not suggest that home- and web-based complex working memory training alters white matter microstructure.

Grey and white matter associations of psychotic-like experiences in a general population sample (UK Biobank)

There has been a substantial amount of research reporting the neuroanatomical associations of psychotic symptoms in people with schizophrenia. Comparatively little attention has been paid to the neuroimaging correlates of subclinical psychotic symptoms, so-called “psychotic-like experiences” (PLEs), within large healthy populations. PLEs are relatively common in the general population (7–13%), can be distressing and negatively affect health. This study therefore examined gray and white matter associations of four different PLEs (auditory or visual PLEs, and delusional ideas about conspiracies or communications) in subjects of the UK Biobank study with neuroimaging data (N = 21,390, mean age = 63 years). We tested for associations between any PLE (N = 768) and individual PLEs with gray and white matter brain structures, controlling for sex, age, intracranial volume, scanning site, and position in the scanner. Individuals that reported having experienced auditory hallucinations (N = 272) were found to have smaller volumes of the caudate, putamen, and accumbens (β = −0.115–0.134, pcorrected = 0.048–0.036), and reduced temporal lobe volume (β = −0.017, pcorrected = 0.047) compared to those that did not. People who indicated that they had ever believed in unreal conspiracies (N = 111) had a larger volume of the left amygdala (β = 0.023, pcorrected = 0.038). Individuals that reported a history of visual PLEs (N = 435) were found to have reduced white matter microstructure of the forceps major (β = −0.029, pcorrected = 0.009), an effect that was more marked in participants who reported PLEs as distressing. These associations were not accounted for by diagnoses of psychotic or depressive illness, nor the known risk factors for psychotic symptoms of childhood adversity or cannabis use. These findings suggest altered regional gray matter volumes and white matter microstructure in association with PLEs in the general population. They further suggest that these alterations may appear more frequently with the presentation of different psychotic symptoms in the absence of clinically diagnosed psychotic disorders.

Brain structural correlates of autistic traits across the diagnostic divide: A grey matter and white matter microstructure study

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental conditions characterised by difficulties in social interaction and communication as well as stereotyped and restricted patterns of interest. Autistic traits exist in a continuum across the general population, whilst the extreme end of this distribution is diagnosed as clinical ASD. While many studies have investigated brain structure in autism using a case-control design, few have used a dimensional approach. To add to this growing body of literature, we investigated the structural brain correlates of autistic traits in a mixed sample of adult participants (25 ASD and 66 neurotypicals; age: 18–60 years). We examined the relationship between regional brain volumes (using voxel-based morphometry and surface-based morphometry) and white matter microstructure properties (using Diffusion Tensor Imaging) and autistic traits (using Autism Spectrum Quotient). Our findings show grey matter differences in regions including the orbitofrontal cortex and lingual gyrus, and suggestive evidence for white matter microstructure differences in tracts including the superior longitudinal fasciculus being related to higher autistic traits. These grey matter and white matter microstructure findings from our study are consistent with previous reports and support the brain structural differences in ASD. These findings provide further support for shared aetiology for autistic traits across the diagnostic divide.

Regional brain volumes, microstructure and neurodevelopment in moderate–late preterm children

ObjectiveTo explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate–late preterm (MLPT).Study designA...

Neonatal Brain Microstructure and Machine-Learning-Based Prediction of Early Language Development in Children Born Very Preterm

BackgroundVery-low-birth-weight preterm infants have a higher rate of language impairments compared with children born full term. Early identification of preterm infants at risk for language delay is essential to guide early intervention at the time of optimal neuroplasticity. This study examined near-term structural brain magnetic resonance imaging (MRI) and white matter microstructure assessed on diffusion tensor imaging (DTI) in relation to early language development in children born very preterm. MethodsA total of 102 very-low-birth-weight neonates (birthweight≤1500g, gestational age ≤32-weeks) were recruited to participate from 2010 to 2011. Near-term structural MRI was evaluated for white matter and cerebellar abnormalities. DTI fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were assessed. Language development was assessed with Bayley Scales of Infant-Toddler Development-III at 18 to 22 months adjusted age. Multivariate models with leave-one-out cross-validation and exhaustive feature selection identified three brain regions most predictive of language function. Distinct logistic regression models predicted high-risk infants, defined by language scores >1 S.D. below average. ResultsOf 102 children, 92 returned for neurodevelopmental testing. Composite language score mean ± S.D. was 89.0 ± 16.0; 31 of 92 children scored <85, including 15 of 92 scoring <70, suggesting moderate-to-severe delay. Children with cerebellar asymmetry had lower receptive language subscores (P = 0.016). Infants at high risk for language impairments were predicted based on regional white matter microstructure on DTI with high accuracy (sensitivity, specificity) for composite (89%, 86%), expressive (100%, 90%), and receptive language (100%, 90%). ConclusionsMultivariate models of near-term structural MRI and white matter microstructure on DTI may assist in identification of preterm infants at risk for language impairment, guiding early intervention.

Microstructural White Matter and Links With Subcortical Structures in Chronic Schizophrenia: A Free-Water Imaging Approach.

Schizophrenia is a severe mental disorder with often a chronic course. Neuroimaging studies report brain abnormalities in both white and gray matter structures. However, the relationship between microstructural white matter differences and volumetric subcortical structures is not known. We investigated 30 long-term treated patients with schizophrenia and schizoaffective disorder (mean age 51.1 ± 7.9 years, mean illness duration 27.6 ± 8.0 years) and 42 healthy controls (mean age 54.1 ± 9.1 years) using 3 T diffusion and structural magnetic resonance imaging. The free-water imaging method was used to model the diffusion signal, and subcortical volumes were obtained from FreeSurfer. We applied multiple linear regression to investigate associations between (i) patient status and regional white matter microstructure, (ii) medication dose or clinical symptoms on white matter microstructure in patients, and (iii) for interactions between subcortical volumes and diagnosis on microstructural white matter regions showing significant patient-control differences. The patients had significantly decreased free-water corrected fractional anisotropy (FAt), explained by decreased axial diffusivity and increased radial diffusivity (RDt) bilaterally in the anterior corona radiata (ACR) and the left anterior limb of the internal capsule (ALIC) compared to controls. In the fornix, the patients had significantly increased RDt. In patients, positive symptoms were associated with localized increased free-water and negative symptoms with localized decreased FAt and increased RDt. There were significant interactions between patient status and several subcortical structures on white matter microstructure and the free-water compartment for left ACR and fornix, and limited to the free-water compartment for right ACR and left ALIC. The Cohen's d effect sizes were medium to large (0.61 to 1.20, absolute values). The results suggest a specific pattern of frontal white matter axonal degeneration and demyelination and fornix demyelination that is attenuated in the presence of larger structures of the limbic system in patients with chronic schizophrenia and schizoaffective disorder. Findings warrant replication in larger samples.

The effect of white matter hyperintensities on regional brain volumes and white matter microstructure, a population-based study in HUNT

Even though age-related white matter hyperintensities (WMH) begin to emerge in middle age, their effect on brain micro- and macrostructure in this age group is not fully elucidated. We have examined how presence of WMH and load of WMH affect regional brain volumes and microstructure in a validated, representative general population sample of 873 individuals between 50 and 66 years. Presence of WMH was determined as Fazakas grade ≥1. WMH load was WMH volume from manual tracing of WMHs divided on intracranial volume. The impact of age appropriate WMH (Fazakas grade 1) on the brain was also investigated. Major novel findings were that even the age appropriate WMH group had widespread macro- and microstructural changes in gray and white matter, showing that the mere presence of WMH, not just WMH load is an important clinical indicator of brain health. With increasing WMH load, structural changes spread centrifugally. Further, we found three major patterns of FA and MD changes related to increasing WMH load, demonstrating a heterogeneous effect on white matter microstructure, where distinct patterns were found in the proximity of the lesions, in deep white matter and in white matter near the cortex. This study also raises several questions about the onset of WMH related pathology, in particular, whether some of the aberrant brain structural and microstructural findings are present before the emergence of WMH. We also found, similar to other studies, that WMH risk factors had low explanatory power for WMH, making it unclear which factors lead to WMH.

Characterisation of brain volume and microstructure at term-equivalent age in infants born across the gestational age spectrum.

BackgroundRisk of morbidity differs between very preterm (VP; <32 weeks' gestational age (GA)), moderate preterm (MP; 32–33 weeks' GA), late preterm (LP; 34–36 weeks' GA), and full-term (FT; ≥37 weeks' GA) infants. However, brain structure at term-equivalent age (TEA; 38–44 weeks) remains to be characterised in all clinically important GA groups. We aimed to compare global and regional brain volumes, and regional white matter microstructure, between VP, MP, LP and FT groups at TEA, in order to establish the magnitude and anatomical locations of between-group differences.MethodsStructural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid (CSF), subcortical grey matter, brainstem and cerebellum. Global tissue volumes were analysed, and additionally, cortical grey matter and white matter volumes were analysed at the regional level using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Statistical analyses involved examining the overall effect of GA group on global volumes (using linear regressions) and regional volumes and microstructure (using non-parametric permutation testing), as well performing post-hoc comparisons between the GA sub-groups.ResultsOn global analysis, cerebrospinal fluid (CSF) volume was larger in all preterm sub-groups compared with the FT group. On regional analysis, volume was smaller in parts of the temporal cortical grey matter, and parts of the temporal white matter and corpus callosum, in all preterm sub-groups compared with the FT group. FA was lower, and RD and MD were higher in voxels located in much of the white matter in all preterm sub-groups compared with the FT group. The anatomical locations of group differences were similar for each preterm vs. FT comparison, but the magnitude and spatial extent of group differences was largest for the VP, followed by the MP, and then the LP comparison. Comparing within the preterm groups, the VP sub-group had smaller frontal and temporal grey and white matter volume, and lower FA and higher MD and RD within voxels in the approximate location of the corpus callosum compared with the MP sub-group. There were few volume and microstructural differences between the MP and LP sub-groups.ConclusionAll preterm sub-groups had atypical brain volume and microstructure at TEA when compared with a FT group, particularly for the CSF, temporal grey and white matter, and corpus callosum. In general, the groups followed a gradient, where the differences were most pronounced for the VP group, less pronounced for the MP group, and least pronounced for the LP group. The VP sub-group was particularly vulnerable compared with the MP and LP sub-groups.

Brain structure and neurological and behavioural functioning in infants born preterm.

To examine: (1) relationships between brain structure, and concurrently assessed neurological and behavioural functioning, in infants born preterm at term-equivalent age (TEA; approximately 38-44wks); and (2) whether brain structure-function relationships differ between infants born very (24-29wks) and moderate-late (32-36wks) preterm. A total of 257 infants (91 very preterm, 166 moderate-late preterm; 120 males, 137 females) had structural magnetic resonance imaging (MRI) and neurological and behavioural assessments (Prechtl's general movements assessment, Neonatal Intensive Care Unit Network Neurobehavioral Scale [NNNS] and Hammersmith Neonatal Neurological Examination [HNNE]). Two hundred and sixty-three infants (90 very preterm, 173 moderate-late preterm; 131 males, 132 females) had diffusion MRI and assessments. Associations were investigated between assessment scores and global brain volumes using linear regressions, regional brain volumes using Voxel-Based Morphometry, and white matter microstructure using Tract-Based Spatial Statistics. Suboptimal scores on some assessments were associated with lower fractional anisotropy and/or higher axial, radial, and mean diffusivities in some tracts: NNNS attention and reflexes, and HNNE total score and tone, were associated with the corpus callosum and optic radiation; NNNS quality of movement with the corona radiata; HNNE abnormal signs with several major tracts. Brain structure-function associations generally did not differ between the very and moderate-late preterm groups. White matter microstructural alterations may be associated with suboptimal neurological and behavioural performance in some domains at TEA in infants born preterm. Brain structure-function relationships are similar for infants born very preterm and moderate-late preterm. Brain volume is not related to neurological/behavioural function in infants born preterm at term. White matter microstructure is related to some neurological/behavioural domains at term. Brain-behaviour relationships are generally similar for infants born very preterm and moderate-late preterm.

Caffeine for apnea of prematurity and brain development at 11years of age.

ObjectiveCaffeine therapy for apnea of prematurity has been reported to improve brain white matter microstructure at term‐equivalent age, but its long‐term effects are unknown. This study aimed to investigate whether caffeine affects (1) brain structure at 11 years of age, and (2) brain development from term‐equivalent age to 11 years of age, compared with placebo.MethodsPreterm infants born ≤1250 g were randomly allocated to caffeine or placebo. Magnetic resonance imaging (MRI) was performed on 70 participants (33 caffeine, 37 placebo) at term‐equivalent age and 117 participants (63 caffeine, 54 placebo) at 11 years of age. Global and regional brain volumes and white matter microstructure were measured at both time points.ResultsIn general, there was little evidence for differences between treatment groups in brain volumes or white matter microstructure at age 11 years. There was, however, evidence that the caffeine group had a smaller corpus callosum than the placebo group. Volumetric brain development from term‐equivalent to 11 years of age was generally similar between treatment groups. However, there was evidence that caffeine was associated with slower growth of the corpus callosum, and slower decreases in axial, radial, and mean diffusivities in the white matter, particularly at the level of the centrum semiovale, over time than placebo.InterpretationThis study suggests any benefits of neonatal caffeine therapy on brain structure in preterm infants weaken over time and are not clearly detectable by MRI at age 11 years, although caffeine may have long‐term effects on corpus callosum development.

Prediction of cognitive and motor development in preterm children using exhaustive feature selection and cross-validation of near-term white matter microstructure.

BackgroundAdvanced neuroimaging and computational methods offer opportunities for more accurate prognosis. We hypothesized that near-term regional white matter (WM) microstructure, assessed on diffusion tensor imaging (DTI), using exhaustive feature selection with cross-validation would predict neurodevelopment in preterm children.MethodsNear-term MRI and DTI obtained at 36.6 ± 1.8 weeks postmenstrual age in 66 very-low-birth-weight preterm neonates were assessed. 60/66 had follow-up neurodevelopmental evaluation with Bayley Scales of Infant-Toddler Development, 3rd-edition (BSID-III) at 18–22 months. Linear models with exhaustive feature selection and leave-one-out cross-validation computed based on DTI identified sets of three brain regions most predictive of cognitive and motor function; logistic regression models were computed to classify high-risk infants scoring one standard deviation below mean.ResultsCognitive impairment was predicted (100% sensitivity, 100% specificity; AUC = 1) by near-term right middle-temporal gyrus MD, right cingulate-cingulum MD, left caudate MD. Motor impairment was predicted (90% sensitivity, 86% specificity; AUC = 0.912) by left precuneus FA, right superior occipital gyrus MD, right hippocampus FA. Cognitive score variance was explained (29.6%, cross-validated Rˆ2 = 0.296) by left posterior-limb-of-internal-capsule MD, Genu RD, right fusiform gyrus AD. Motor score variance was explained (31.7%, cross-validated Rˆ2 = 0.317) by left posterior-limb-of-internal-capsule MD, right parahippocampal gyrus AD, right middle-temporal gyrus AD.ConclusionSearch in large DTI feature space more accurately identified neonatal neuroimaging correlates of neurodevelopment.