Analysis of different hematoma expansion shapes caused by different risk factors in patients with hypertensive intracerebral hemorrhage.

OBJECTIVE: To elucidate the relationship between the risk factors and hematoma expansion(HE)shapes. PATIENTS AND METHODS: From February 2013 to November 2018, 60 patients diagnosed as basal ganglia ICH were divided into the filled type hematoma expansion group (FTE group) and the expanded type hematoma expansion group (ETE group). we performed follow-up CT and three-dimensional reconstruction for the patients and compared the hematoma before and after the expansion of size and extent. RESULTS: The regression analysis showed that the irregular sign (odds ratio, 3.64; 95 % CI, 1.46-9.12), black hole sign (odds ratio, 3.85; 95 % CI, 1.40-10.60), blend sign (odds ratio, 2.86; 95 % CI, 1.03-7.95), and early use of dehydration (odds ratio, 4.59; 95 % CI, 1.59-13.19) were possible risk factors for the ETE group, while the high systolic blood pressure (odds ratio, 1.51; 95 % CI, 1.04-2.30), early use of dehydration (odds ratio, 3.27; 95 % CI, 1.10-9.69) and low density low-density band (odds ratio, 4.52; 95 % CI, 1.54-13.28) were possible risk factors for the FTE group. CONCLUSIONS: The irregular sign, black hole sign, blend sign and early use of dehydration may be the main risk factors for ETE, whereas early use of dehydration, high systolic blood pressure, and low density low-density band may be the main risk factors for FTE.

Cumulative Blood Pressure Exposure, Basal Ganglia, and Thalamic Morphology in Midlife.

High blood pressure (BP) negatively affects brain structure and function. Hypertension is associated with white matter hyperintensities, cognitive and mobility impairment in late-life. However, the impact of BP exposure from young adulthood on brain structure and function in mid-life is unclear. Identifying early brain structural changes associated with BP exposure, before clinical onset of cognitive dysfunction and mobility impairment, is essential for understanding mechanisms and developing interventions. We examined the effect of cumulative BP exposure from young adulthood on brain structure in a substudy of 144 (61 female) individuals from the CARDIA (Coronary Artery Risk Development in Young Adults) study. At year 30 (Y30, ninth visit), participants (56±4 years old) completed brain magnetic resonance imaging and gait measures (pace, rhythm, and postural control). Cumulative systolic and diastolic BP (cumulative systolic blood pressure, cDBP) over 9 visits were calculated, multiplying mean values between 2 consecutive visits by years between visits. Surface-based analysis of basal ganglia and thalamus was achieved using FreeSurfer-initiated Large Deformation Diffeomorphic Metric Mapping. Morphometric changes were regressed onto cumulative BP to localize regions of shape variation. Y30 white matter hyperintensity volumes were small and positively correlated with cumulative BP but not gait. Negative morphometric associations with cumulative systolic blood pressure were seen in the caudate, putamen, nucleus accumbens, pallidum, and thalamus. A concave right medial putamen shape mediated the relationship between cumulative systolic blood pressure and stride width. Basal ganglia and thalamic morphometric changes, rather than volumes, may be earlier manifestation of gray matter structural signatures of BP exposure that impact midlife gait.

Longitudinal Development of Brain Iron Is Linked to Cognition in Youth.

Brain iron is vital to multiple aspects of brain function, including oxidative metabolism, myelination, and neurotransmitter synthesis. Atypical iron concentration in the basal ganglia is associated with neurodegenerative disorders in aging and cognitive deficits. However, the normative development of brain iron concentration in adolescence and its relationship to cognition are less well understood. Here, we address this gap in a longitudinal sample of 922 humans aged 8-26 years at the first visit (M = 15.1, SD = 3.72; 336 males, 486 females) with up to four multiecho T2* scans each. Using this sample of 1236 imaging sessions, we assessed the longitudinal developmental trajectories of tissue iron in the basal ganglia. We quantified tissue iron concentration using R2* relaxometry within four basal ganglia regions, including the caudate, putamen, nucleus accumbens, and globus pallidus. The longitudinal development of R2* was modeled using generalized additive mixed models (GAMMs) with splines to capture linear and nonlinear developmental processes. We observed significant increases in R2* across all regions, with the greatest and most prolonged increases occurring in the globus pallidus and putamen. Further, we found that the developmental trajectory of R2* in the putamen is significantly related to individual differences in cognitive ability, such that greater cognitive ability is increasingly associated with greater iron concentration through late adolescence and young-adulthood. Together, our results suggest a prolonged period of basal ganglia iron enrichment that extends into the mid-twenties, with diminished iron concentration associated with poorer cognitive ability during late adolescence.SIGNIFICANCE STATEMENT Brain tissue iron is essential to healthy brain function. Atypical basal ganglia tissue iron levels have been linked to impaired cognition in iron deficient children and adults with neurodegenerative disorders. However, the normative developmental trajectory of basal ganglia iron concentration during adolescence and its association with cognition are less well understood. In the largest study of tissue iron development yet reported, we characterize the developmental trajectory of tissue iron concentration across the basal ganglia during adolescence and provide evidence that diminished iron content is associated with poorer cognitive performance even in healthy youth. These results highlight the transition from adolescence to adulthood as a period of dynamic maturation of tissue iron concentration in the basal ganglia.

Basal ganglia and thalamic tract connectivity in very preterm and full-term children; associations with 7-year neurodevelopment.

BACKGROUND: Altered basal ganglia and thalamic connectivity may be critical for cognitive, motor and behavioural impairments common to very preterm (<32 weeks' gestational age) children. This study aims to (1) compare corticostriatal and thalamocortical tract connectivity between very preterm and term-born children at 7 years of age; (2) explore tract connectivity associations with 7-year neurodevelopmental outcomes, and whether these relationships differed between groups. METHODS: Eighty-three very preterm and 19 term-born (≥37 weeks' gestational age) children underwent structural and diffusion magnetic resonance imaging and had a neuropsychological assessment at 7 years. Corticostriatal and thalamocortical tracts were reconstructed and white matter connectivity was estimated with apparent fibre density. RESULTS: Compared with term-born controls, very preterm children had decreased connectivity in tracts linking the caudate to right motor areas (-10%, p = 0.03) and the thalamus with left motor areas (-5.7%, p = 0.03). Reduced connectivity in corticostriatal and thalamocortical tracts was associated with adverse motor functioning in both groups (p = 0.06). Decreased connectivity of the left caudate and putamen with the lateral prefrontal cortex was associated with lower reading performance for controls (p = 0.06). CONCLUSION: Corticostriatal and thalamocortical tracts are vulnerable to very preterm birth. Poorer connectivity in these tracts may underlie the motor impairments observed in very preterm children.

Sex-Based Differences in Cortical and Subcortical Development in 436 Individuals Aged 4-54 Years.

Sex-based differences in brain development have long been established in ex vivo studies. Recent in vivo studies using magnetic resonance imaging (MRI) have offered considerable insight into sex-based variations in brain maturation. However, reports of sex-based differences in cortical volumes and thickness are inconsistent. We examined brain maturation in a cross-sectional, single-site cohort of 436 individuals (201 [46%] males) aged 4-54 years (median = 16 years). Cortical thickness, cortical surface area, subcortical surface area, volumes of the cerebral cortex, white matter (WM), cortical and subcortical gray matter (GM), including the thalamic subnuclei, basal ganglia, and hippocampi were calculated using automatic segmentation pipelines. Subcortical structures demonstrated distinct curvilinear trajectories from the cortex, in both volumetric maturation and surface-area expansion in relation to age. Surface-area analysis indicated that dorsal regions of the thalamus, globus pallidus and striatum, regions demonstrating structural connectivity with frontoparietal cortices, exhibited extensive expansion with age, and were inversely related to changes seen in cortical maturation, which contracted with age. Furthermore, surface-area expansion was more robust in males in comparison to females. Age- and sex-related maturational changes may reflect alterations in dendritic and synaptic architecture known to occur during development from early childhood through to mid-adulthood.

Agenesis of the putamen and globus pallidus caused by recessive mutations in the homeobox gene GSX2.

Basal ganglia are subcortical grey nuclei that play essential roles in controlling voluntary movements, cognition and emotion. While basal ganglia dysfunction is observed in many neurodegenerative or metabolic disorders, congenital malformations are rare. In particular, dysplastic basal ganglia are part of the malformative spectrum of tubulinopathies and X-linked lissencephaly with abnormal genitalia, but neurodevelopmental syndromes characterized by basal ganglia agenesis are not known to date. We ascertained two unrelated children (both female) presenting with spastic tetraparesis, severe generalized dystonia and intellectual impairment, sharing a unique brain malformation characterized by agenesis of putamina and globi pallidi, dysgenesis of the caudate nuclei, olfactory bulbs hypoplasia, and anomaly of the diencephalic-mesencephalic junction with abnormal corticospinal tract course. Whole-exome sequencing identified two novel homozygous variants, c.26C>A; p.(S9*) and c.752A>G; p.(Q251R) in the GSX2 gene, a member of the family of homeobox transcription factors, which are key regulators of embryonic development. GSX2 is highly expressed in neural progenitors of the lateral and median ganglionic eminences, two protrusions of the ventral telencephalon from which the basal ganglia and olfactory tubercles originate, where it promotes neurogenesis while negatively regulating oligodendrogenesis. The truncating variant resulted in complete loss of protein expression, while the missense variant affected a highly conserved residue of the homeobox domain, was consistently predicted as pathogenic by bioinformatic tools, resulted in reduced protein expression and caused impaired structural stability of the homeobox domain and weaker interaction with DNA according to molecular dynamic simulations. Moreover, the nuclear localization of the mutant protein in transfected cells was significantly reduced compared to the wild-type protein. Expression studies on both patients' fibroblasts demonstrated reduced expression of GSX2 itself, likely due to altered transcriptional self-regulation, as well as significant expression changes of related genes such as ASCL1 and PAX6. Whole transcriptome analysis revealed a global deregulation in genes implicated in apoptosis and immunity, two broad pathways known to be involved in brain development. This is the first report of the clinical phenotype and molecular basis associated to basal ganglia agenesis in humans.

Synaptic Wiring of Corticostriatal Circuits in Basal Ganglia: Insights into the Pathogenesis of Neuropsychiatric Disorders.

The striatum is a key hub in the basal ganglia for processing neural information from the sensory, motor, and limbic cortices. The massive and diverse cortical inputs entering the striatum allow the basal ganglia to perform a repertoire of neurological functions ranging from basic level of motor control to high level of cognition. The heterogeneity of the corticostriatal circuits, however, also renders the system susceptible to a repertoire of neurological diseases. Clinical and animal model studies have indicated that defective development of the corticostriatal circuits is linked to various neuropsychiatric disorders, including attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, obsessive-compulsive disorder (OCD), autism spectrum disorder (ASD), and schizophrenia. Importantly, many neuropsychiatric disease-risk genes have been found to form the molecular building blocks of the circuit wiring at the synaptic level. It is therefore imperative to understand how corticostriatal connectivity is established during development. Here, we review the construction during development of these corticostriatal circuits at the synaptic level, which should provide important insights into the pathogenesis of neuropsychiatric disorders related to the basal ganglia and help the development of appropriate therapies for these diseases.

Differential developmental changes in cortical representations of auditory-vocal stimuli in songbirds.

Procedural skill learning requires iterative comparisons between feedback of self-generated motor output and a goal sensorimotor pattern. In juvenile songbirds, neural representations of both self-generated behaviors (each bird's own immature song) and the goal motor pattern (each bird's adult tutor song) are essential for vocal learning, yet little is known about how these behaviorally relevant stimuli are encoded. We made extracellular recordings during song playback in anesthetized juvenile and adult zebra finches ( Taeniopygia guttata) in adjacent cortical regions RA (robust nucleus of the arcopallium), AId (dorsal intermediate arcopallium), and RA cup, each of which is well situated to integrate auditory-vocal information: RA is a motor cortical region that drives vocal output, AId is an adjoining cortical region whose projections converge with basal ganglia loops for song learning in the dorsal thalamus, and RA cup surrounds RA and receives inputs from primary and secondary auditory cortex. We found strong developmental differences in neural selectivity within RA, but not in AId or RA cup. Juvenile RA neurons were broadly responsive to multiple songs but preferred juvenile over adult vocal sounds; in addition, spiking responses lacked consistent temporal patterning. By adulthood, RA neurons responded most strongly to each bird's own song with precisely timed spiking activity. In contrast, we observed a complete lack of song responsivity in both juvenile and adult AId, even though this region receives song-responsive inputs. A surprisingly large proportion of sites in RA cup of both juveniles and adults did not respond to song playback, and responsive sites showed little evidence of song selectivity. NEW & NOTEWORTHY Motor skill learning entails changes in selectivity for behaviorally relevant stimuli across cortical regions, yet the neural representation of these stimuli remains understudied. We investigated how information important for vocal learning in zebra finches is represented in regions analogous to infragranular layers of motor and auditory cortices during vs. after the developmentally regulated learning period. The results provide insight into how neurons in higher level stages of cortical processing represent stimuli important for motor skill learning.

Transplantation of Adipose Tissue-Derived Stem Cells into Brain Through Cerebrospinal Fluid in Rat Models: Protocol Development and Initial Outcome Data.

BACKGROUND: Cell therapy is an important strategy for the treatment of incurable diseases including those that occur in the Central Nervous System (CNS). Among different strategies, the method of delivering or transplantation of cells into the brain has shown significant effects on regeneration. In this study, a new protocol has been developed for the transplantation of adipose tissuederived stem cells into the brain through Cerebrospinal Fluid (CSF) in rat models. METHODS: For this purpose, a wide range of ages (7-30 days old) of male neonates of Wistar rats was used. Moreover, human adipose tissue was obtained from a superficial layer of abdomen through liposuction surgery. The size of the inserted part of needle to access middle cranial fossa and subarachnoid space in animals with an average weight of 10-80 g was determined. In addition, to confirm the entrance of needle into the subarachnoid space, CSF was aspirated slowly and then injection was done within two minutes. RESULTS: The findings showed the presence of transplanted human Adipose-Derived Stem Cells (hADSC) in the cerebellum and basal ganglia following three days and also after two months that confirmed the entrance of transplanted cells into the cerebrospinal fluid and migration of them into the brain tissue. All the animals survived after the transplantation process, with the lowest side effects compared to the available conventional methods. CONCLUSION: It can be concluded that the cells could be efficiently transplanted into CSF through subarachnoid space by injection via superior orbital fissure with a minimally invasive technique.

Rapid high resolution T1 mapping as a marker of brain development: Normative ranges in key regions of interest.

OBJECTIVES: We studied in a clinical setting the age dependent T1 relaxation time as a marker of normal late brain maturation and compared it to conventional techniques, namely the apparent diffusion coefficient (ADC). MATERIALS AND METHODS: Forty-two healthy subjects ranging from ages 1 year to 20 years were included in our study. T1 brain maps in which the intensity of each pixel corresponded to T1 relaxation times were generated based on MR imaging data acquired using a MP2RAGE sequence. During the same session, diffusion tensor imaging data was collected. T1 relaxation times and ADC in white matter and grey matter were measured in seven clinically relevant regions of interest and were correlated to subjects' age. RESULTS: In the basal ganglia, there was a small, yet significant, decrease in T1 relaxation time (-0.45 ≤R≤-0.59, p<10-2) and ADC (-0.60≤R≤-0.65, p<10-4) as a function of age. In the frontal and parietal white matter, there was a significant decrease in T1 relaxation time (-0.62≤R≤-0.68, p<10-4) and ADC (-0.81≤R≤-0.85, p<10-4) as a function of age. T1 relaxation time changes in the corpus callosum and internal capsule were less relevant for this age range. There was no significant difference between the correlation of T1 relaxation time and ADC with respect to age (p-value = 0.39). The correlation between T1 relaxation and ADC is strong in the white matter but only moderate in basal ganglia over this age period. CONCLUSIONS: T1 relaxation time is a marker of brain maturation or myelination during late brain development. Between the age of 1 and 20 years, T1 relaxation time decreases as a function of age in the white matter and basal ganglia. The greatest changes occur in frontal and parietal white matter. These regions are known to mature in the final stage of development and are mainly composed of association circuits. Age-correlation is not significantly different between T1 relaxation time and ADC. Therefore, T1 relaxation time does not appear to be a superior marker of brain maturation than ADC but may be considered as complementary owing the intrinsic differences in bio-physical sensitivity. This work may serve as normative ranges in clinical imaging routines.

Maternal Immune Activation During the Third Trimester Is Associated with Neonatal Functional Connectivity of the Salience Network and Fetal to Toddler Behavior.

Prenatal maternal immune activation (MIA) is associated with altered brain development and risk of psychiatric disorders in offspring. Translational human studies of MIA are few in number. Alterations of the salience network have been implicated in the pathogenesis of the same psychiatric disorders associated with MIA. If MIA is pathogenic, then associated abnormalities in the salience network should be detectable in neonates immediately after birth. We tested the hypothesis that third trimester MIA of adolescent women who are at risk for high stress and inflammation is associated with the strength of functional connectivity in the salience network of their neonate. Thirty-six women underwent blood draws to measure interleukin-6 (IL-6) and C-reactive protein (CRP) and electrocardiograms to measure fetal heart rate variability (FHRV) at 34-37 weeks gestation. Resting-state imaging data were acquired in the infants at 40-44 weeks postmenstrual age (PMA). Functional connectivity was measured from seeds placed in the anterior cingulate cortex and insula. Measures of cognitive development were obtained at 14 months PMA using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Both sexes were studied. Regions in which the strength of the salience network correlated with maternal IL-6 or CRP levels included the medial prefrontal cortex, temporoparietal junction, and basal ganglia. Maternal CRP level correlated inversely with FHRV acquired at the same gestational age. Maternal CRP and IL-6 levels correlated positively with measures of cognitive development on the BSID-III. These results suggest that MIA is associated with short- and long-term influences on offspring brain and behavior.SIGNIFICANCE STATEMENT Preclinical studies in rodents and nonhuman primates and epidemiological studies in humans suggest that maternal immune activation (MIA) alters the development of brain circuitry and associated behaviors, placing offspring at risk for psychiatric illness. Consistent with preclinical findings, we show that maternal third trimester interleukin-6 and C-reactive protein levels are associated with neonatal functional connectivity and with both fetal and toddler behavior. MIA-related functional connectivity was localized to the salience, default mode, and frontoparietal networks, which have been implicated in the pathogenesis of psychiatric disorders. Our results suggest that MIA alters functional connectivity in the neonatal brain, that those alterations have consequences for cognition, and that these findings may provide pathogenetic links between preclinical and epidemiological studies associating MIA with psychiatric risk in offspring.

Nutrient Intake in the First Two Weeks of Life and Brain Growth in Preterm Neonates.

BACKGROUND: Optimizing early nutritional intake in preterm neonates may promote brain health and neurodevelopment through enhanced brain maturation. Our objectives were (1) to determine the association of energy and macronutrient intake in the first 2 weeks of life with regional and total brain growth and white matter (WM) maturation, assessed by 3 serial MRI scans in preterm neonates; (2) to examine how critical illness modifies this association; and (3) to investigate the relationship with neurodevelopmental outcomes. METHODS: Forty-nine preterm neonates (21 boys, median [interquartile range] gestational age: 27.6 [2.3] weeks) were scanned serially at the following median postmenstrual weeks: 29.4, 31.7, and 41. The total brain, basal nuclei, and cerebellum were semiautomatically segmented. Fractional anisotropy was extracted from diffusion tensor imaging data. Nutritional intake from day of life 1 to 14 was monitored and clinical factors were collected. RESULTS: Greater energy and lipid intake predicted increased total brain and basal nuclei volumes over the course of neonatal care to term-equivalent age. Similarly, energy and lipid intake were significantly associated with fractional anisotropy values in selected WM tracts. The association of ventilation duration with smaller brain volumes was attenuated by higher energy intake. Brain growth predicted psychomotor outcome at 18 months' corrected age. CONCLUSIONS: In preterm neonates, greater energy and enteral feeding during the first 2 weeks of life predicted more robust brain growth and accelerated WM maturation. The long-lasting effect of early nutrition on neurodevelopment may be mediated by enhanced brain growth. Optimizing nutrition in preterm neonates may represent a potential avenue to mitigate the adverse brain health consequences of critical illness.

Basal ganglia: Their role in complex cognitive procedures in experimental models and in clinical practice.

Apart from the well known role of the basal ganglia (BG) in motor control, their important role in regulating the cognitive functions is emerging. This article traces the scientific work that explores this role of BG in reinforcement learning, perceptual decision making, and other nonmotor pathways (speech fluency, cognition, attention and behaviour). It also highlights the important role played by the BG networks in determining the development of a child's brain. It retraces the various pathways and connections of the BG with the cerebral cortex, cerebellum and other regions that may be utilized in the establishment of complex cognitive procedures. Various diseases that may be the direct result of disruption of these basal ganglionic networks and interconnections are also recounted.

MRI Differences Associated with Intrauterine Growth Restriction in Preterm Infants.

BACKGROUND: Preterm infants are at risk for neurodevelopmental impairment. Intrauterine growth restriction (IUGR) further increases this risk. Brain imaging studies are often utilized at or near term-equivalent age to determine later prognosis. OBJECTIVE: To evaluate the association between intrauterine growth and regional brain volume on MRI scans performed in preterm infants at or near term-equivalent age. METHODS: This is a retrospective case-control study of 24 infants born at gestational age ≤30 weeks and cared for in a large, inner-city, academic neonatal intensive-care unit from 2012 to 2013. Each IUGR infant was matched with 1-2 appropriate for gestational age (AGA) infants who served as controls. Predischarge MRI scans routinely obtained at ≥36 weeks' adjusted age were analyzed for regional brain volumetric differences. We examined the association between IUGR and thalamic, basal ganglion, and cerebellar brain volumes in these preterm infants. RESULTS: Compared to AGA infants, IUGR infants had a smaller thalamus (7.88 vs. 5.87 mL, p = 0.001) and basal ganglion (8.87 vs. 6.92 mL, p = 0.002) volumes. There was no difference in cerebellar volumes between the two study groups. Linear regression analyses revealed similar trends in the associations between IUGR and brain volumes after adjusting for sex, gestational age at birth, and postconceptual age and weight at MRI. CONCLUSIONS: Thalamus and basal ganglion volumes are reduced in growth-restricted preterm infants. These differences may preferentially impact neurodevelopmental outcomes. Further research is needed to explore these relationships.

Magnetization Transfer and Amide Proton Transfer MRI of Neonatal Brain Development.

Purpose. This study aims to evaluate the process of brain development in neonates using combined amide proton transfer (APT) imaging and conventional magnetization transfer (MT) imaging. Materials and Methods. Case data were reviewed for all patients hospitalized in our institution's neonatal ward. Patients underwent APT and MT imaging (a single protocol) immediately following the routine MR examination. Single-slice APT/MT axial imaging was performed at the level of the basal ganglia. APT and MT ratio (MTR) measurements were performed in multiple brain regions of interest (ROIs). Data was statistically analyzed in order to assess for significant differences between the different regions of the brain or correlation with patient gestational age. Results. A total of 38 neonates were included in the study, with ages ranging from 27 to 41 weeks' corrected gestational age. There were statistically significant differences in both APT and MTR measurements between the frontal lobes, basal ganglia, and occipital lobes (APT: frontal lobe versus occipital lobe P = 0.031 and other groups P = 0.00; MTR: frontal lobe versus occipital lobe P = 0.034 and other groups P = 0.00). Furthermore, APT and MTR in above brain regions exhibited positive linear correlations with patient gestational age. Conclusions. APT/MT imaging can provide valuable information about the process of the neonatal brain development at the molecular level.

Subpallial Enhancer Transgenic Lines: a Data and Tool Resource to Study Transcriptional Regulation of GABAergic Cell Fate.

Elucidating the transcriptional circuitry controlling forebrain development requires an understanding of enhancer activity and regulation. We generated stable transgenic mouse lines that express CreERT2 and GFP from ten different enhancer elements with activity in distinct domains within the embryonic basal ganglia. We used these unique tools to generate a comprehensive regional fate map of the mouse subpallium, including sources for specific subtypes of amygdala neurons. We then focused on deciphering transcriptional mechanisms that control enhancer activity. Using machine-learning computations, in vivo chromosomal occupancy of 13 transcription factors that regulate subpallial patterning and differentiation and analysis of enhancer activity in Dlx1/2 and Lhx6 mutants, we elucidated novel molecular mechanisms that regulate region-specific enhancer activity in the developing brain. Thus, these subpallial enhancer transgenic lines are data and tool resources to study transcriptional regulation of GABAergic cell fate.

The developing human brain: age-related changes in cortical, subcortical, and cerebellar anatomy.

INTRODUCTION: This study is the first to characterize normal development and sex differences across neuroanatomical structures in cortical, subcortical, and cerebellar brain regions in a single large cohort. METHODS: One hundred and ninety-two magnetic resonance images were examined from 96 typically developing females and 96 age-matched typically developing males from 4 to 18 years of age. Image segmentation of the cortex was conducted with CIVET, while that of the cerebellum, hippocampi, thalamus, and basal ganglia were conducted using the MAGeT algorithm. RESULTS: Cortical thickness analysis revealed that most cortical regions decrease linearly, while surface area increases linearly with age. Volume relative to total cerebrum followed a quadratic trend with age, with only the left supramarginal gyrus showing sexual dimorphism. Hippocampal relative volume increased linearly, while the thalamus, caudate, and putamen decreased linearly, and the cerebellum did not change with age. The relative volumes of several subcortical subregions followed inverted U-shaped trends that peaked at ~12 years of age. Many subcortical structures were found to be larger in females than in males, independently of age, while others showed a sex-by-age interaction. CONCLUSION: This study provides a comprehensive assessment of cortical, subcortical, and cerebellar growth patterns during normal development, and draws attention to the role of sex on neuroanatomical maturation throughout childhood and adolescence.

Cell adhesion molecule contactin-associated protein 3 is expressed in the mouse basal ganglia during early postnatal stages.

Cell adhesion molecules play important roles in the development of the nervous system. Among the contactin-associated protein (Caspr; also known as Cntnap) family, which belongs to the neurexin superfamily of proteins, Caspr and Caspr2 are indispensable for the formation and maintenance of myelinated nerves. In contrast, a physiological role for Caspr3 remains to be elucidated. This study examines the expression and localization of Caspr3 in the mouse brain using newly generated Caspr3 antibodies. Caspr3 was expressed abundantly between the first and the second postnatal weeks. During this period, Caspr3 was localized especially to the basal ganglia, including the striatum, external segment of the globus pallidus, and substantia nigra, and no gross abnormalities were apparent in the basal ganglia of Caspr3 knockout mice. In the striatum, Caspr3 was expressed by a subpopulation of medium spiny neurons that constitute the direct and indirect pathways. Caspr3 immunostaining was observed as punctate around the cell bodies as well as in the soma. These Caspr3 signals did not, however, overlap with those of synaptic markers. Our findings suggest that Caspr3 may play an important role in basal ganglia development during early postnatal stages.

Subcortical glutamate mediates the reduction of short-range functional connectivity with age in a developmental cohort.

Marked changes in brain physiology and structure take place between childhood and adulthood, including changes in functional connectivity and changes in the balance between main excitatory and inhibitory neurotransmitters glutamate (Glu) and GABA. The balance of these neurotransmitters is thought to underlie neural activity in general and functional connectivity networks in particular, but so far no studies have investigated the relationship between human development related differences in these neurotransmitters and concomitant changes in functional connectivity. GABA+/H2O and Glu/H2O levels were acquired in a group of healthy children, adolescents, and adults in a subcortical (basal ganglia) region, as well as in a frontal region in adolescents and adults. Our results showed higher GABA+/Glu with age in both the subcortical and the frontal voxel, which were differentially associated with significantly lower Glu/H2O with age in the subcortical voxel and by significantly higher GABA+/H2O with age in the frontal voxel. Using a seed-to-voxel analysis, we were further able to show that functional connectivity between the putamen (seed) and other subcortical structures was lower with age. Lower subcortical Glu/H2O with age mediated the lower connectivity in the dorsal putamen. Based on these results, and the potential role of Glu in synaptic pruning, we suggest that lower Glu mediates a reduction of local connectivity during human development.

Deep grey matter growth predicts neurodevelopmental outcomes in very preterm children.

We evaluated whether the volume and growth rate of critical brain structures measured by MRI in the first weeks of life following very preterm (<32/40 weeks) birth could predict subsequent neurodevelopmental outcomes at 4 years of age. A significant proportion of children born very prematurely have cognitive deficits, but these problems are often only detected at early school age. Structural T2-weighted magnetic resonance images were acquired in 96 very preterm neonates scanned within 2 weeks of birth and 70 of these at term-equivalent age. An automated 3D image analysis procedure was used to measure the volume of selected brain structures across all scans and time points. At 4 years of age, 53 children returned for neuropsychological assessments evaluating IQ, language and visual motor integration. Associations with maternal education and perinatal measures were also explored. Multiple regression analyses revealed that growth of the caudate and globus pallidus between preterm birth and term-equivalent age predicted visual motor integration scores after controlling for sex and gestational age. Further associations were found between caudate and putamen growth with IQ and language scores. Analyses at either preterm or term-equivalent age only found associations between normalized deep grey matter growth and visual motor integration scores at term-equivalent age. Maternal education levels were associated with measures of IQ and language, but not visual motor integration. Thalamic growth was additionally linked with perinatal measures and presence of white matter lesions. These results highlight deep grey matter growth rates as promising biomarkers of long-term outcomes following very preterm birth, and contribute to our understanding of the brain-behaviour relations in these children.