A three-step, "brute-force" approach toward optimized affine spatial normalization.

The first step in spatial normalization of magnetic resonance (MR) images commonly is an affine transformation, which may be vulnerable to image imperfections (such as inhomogeneities or "unusual" heads). Additionally, common software solutions use internal starting estimates to allow for a more efficient computation, which may pose a problem in datasets not conforming to these assumptions (such as those from children). In this technical note, three main questions were addressed: one, does the affine spatial normalization step implemented in SPM12 benefit from an initial inhomogeneity correction. Two, does using a complexity-reduced image version improve robustness when matching "unusual" images. And three, can a blind "brute-force" application of a wide range of parameter combinations improve the affine fit for unusual datasets in particular. A large database of 2081 image datasets was used, covering the full age range from birth to old age. All analyses were performed in Matlab. Results demonstrate that an initial removal of image inhomogeneities improved the affine fit particularly when more inhomogeneity was present. Further, using a complexity-reduced input image also improved the affine fit and was beneficial in younger children in particular. Finally, blindly exploring a very wide parameter space resulted in a better fit for the vast majority of subjects, but again particularly so in infants and young children. In summary, the suggested modifications were shown to improve the affine transformation in the large majority of datasets in general, and in children in particular. The changes can easily be implemented into SPM12.

The long-term negative impact of childhood stroke on language.

Objectives: This study aims to investigate the long-term language outcome in children with unilateral childhood stroke in comparison to those with perinatal strokes and typically developing individuals and to explore the impact of lesion-specific modifiers. Methods: We examined nine patients with childhood stroke, acquired between 0;2 and 16;1 years (CHILD; 3 female, median = 13.5 years, 6 left-sided), 23 patients with perinatal strokes (PERI; 11 female, median = 12.5 years, 16 left-sided), and 33 age-matched typically developing individuals (CONTROL; 15 female, median = 12.33 years). The language outcome was assessed using age-appropriate tasks of the Potsdam Illinois Test of Psycholinguistic Abilities (P-ITPA) or the Peabody Picture Vocabulary Test (PPVT). For group comparisons, study-specific language z-scores were calculated. Non-verbal intelligence was assessed using the Test of Non-verbal Intelligence (TONI-4), language lateralization with functional MRI, and lesion size with MRI-based volumetry. Results: All four patients with childhood stroke who initially presented with aphasic symptoms recovered from aphasia. Patients with childhood stroke showed significantly lower language scores than those in the control group, but their scores were similar to those of the patients with perinatal stroke, after adjusting for general intelligence (ANCOVA, language z-score CHILD = -0.30, PERI = -0.38, CONTROL = 0.42). Among the patients with childhood stroke, none of the possible modifying factors, including lesion side, correlated significantly with the language outcome. Conclusion: Childhood stroke, regardless of the affected hemisphere, can lead to chronic language deficits, even though affected children show a "full recovery." The rehabilitation of children and adolescents with childhood stroke should address language abilities, even after the usually quick resolution of clear aphasic symptoms.

[Learning from Errors: Qualitative Analysis of Expert Reports on Malpractice in Family Medicine]. / Aus Fehlern lernen ­ qualitative Analyse von Gutachten zu hausärztlichen Behandlungsfehlern.

BACKGROUND: Expert committees of the German medical associations provide a free and out-of-court evaluation of putative cases of medical malpractice. They prepare reports that contain valuable information on process steps that precede the actual treatment error. The aim of the present study was to identify and systematically categorize individual process steps in the expert reports and thus to lay the foundations for the understanding of malpractice evaluation processes. METHODS: In this study, ten randomly selected and anonymized expert reports of the Expert Committee for Questions of Medical Liability of the District Medical Association of South Württemberg with identified GP treatment errors were evaluated, using the method of qualitative content analysis. In an iterative process, central elements of expert reports were classified into a deductively and inductively built category system. RESULTS: Six main categories with associated subcategories were identified: 1) structural aspects of the report, 2) doctor-patient communication, 3) medical course, 4) patient's experience, 5) action by the GP team, and 6) coordinative role in the health care system. The category system showed sufficient reliability with repeated use. CONCLUSION: This study offers an opportunity to learn from errors. The proposed system allows to structure the complexity of expert reports on GP malpractice and may thus serve as a tool in various contexts. In particular, it facilitates the preparation and comparative analysis of reports in a structured way. It could also be used in health care research as well as in education and training.

Atypical language organization following perinatal infarctions of the left hemisphere is associated with structural changes in right-hemispheric grey matter.

AIM: To assess how atypical language organization after early left-hemispheric brain lesions affects grey matter in the contralesional hemisphere. METHOD: This was a cross-sectional study with between-group comparisons of 14 patients (six female, 8-26 years) with perinatal left-hemispheric brain lesions (two arterial ischemic strokes, 11 periventricular haemorrhagic infarctions, one without classification) and 14 typically developing age-matched controls (TDC) with functional magnetic resonance imaging (fMRI) documented left-hemispheric language organization (six female, 8-28 years). MRI data were analysed with SPM12, CAT12, and custom scripts. Language lateralization indices were determined by fMRI within a prefrontal mask and right-hemispheric grey matter group differences by voxel-based morphometry (VBM). RESULTS: FMRI revealed left-dominance in seven patients with typical language organization (TYP) and right-dominance in seven patients with atypical language organization (ATYP) of 14 patients. VBM analysis of all patients versus controls showed grey matter reductions in the middle temporal gyrus of patients. A comparison between the two patient subgroups revealed an increase of grey matter in the middle frontal gyrus in the ATYP group. Voxel-based regression analysis confirmed that grey matter increases in the middle frontal gyrus were correlated with atypical language organization. INTERPRETATION: Compatible with a non-specific lesion effect, we found areas of grey matter reduction in patients as compared to TDC. The grey matter increase in the middle frontal gyrus seems to reflect a specific compensatory effect in patients with atypical language organization. WHAT THIS PAPER ADDS: Perinatal stroke leads to decreased grey matter in the contralesional hemisphere. Atypical language organization is associated with grey matter increases in contralesional language areas.

Reduced structural connectivity in non-motor networks in children born preterm and the influence of early postnatal human cytomegalovirus infection.

Introduction: Preterm birth is increasingly recognized to cause lifelong functional deficits, which often show no correlate in conventional MRI. In addition, early postnatal infection with human cytomegalovirus (hCMV) is being discussed as a possible cause for further impairments. In the present work, we used fixel-based analysis of diffusion-weighted MRI to assess long-term white matter alterations associated with preterm birth and/or early postnatal hCMV infection. Materials and methods: 36 former preterms (PT, median age 14.8 years, median gestational age 28 weeks) and 18 healthy term-born controls (HC, median age 11.1 years) underwent high angular resolution DWI scans (1.5 T, b = 2 000 s/mm2, 60 directions) as well as clinical assessment. All subjects showed normal conventional MRI and normal motor function. Early postnatal hCMV infection status (CMV+ and CMV-) had been determined from repeated screening, ruling out congenital infections. Whole-brain analysis was performed, yielding fixel-wise metrics for fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). Group differences were identified in a whole-brain analysis, followed by an analysis of tract-averaged metrics within a priori selected tracts associated with cognitive function. Both analyses were repeated while differentiating for postnatal hCMV infection status. Results: PT showed significant reductions of fixel metrics bilaterally in the cingulum, the genu corporis callosum and forceps minor, the capsula externa, and cerebellar and pontine structures. After including intracranial volume as a covariate, reductions remained significant in the cingulum. The tract-specific investigation revealed further reductions bilaterally in the superior longitudinal fasciculus and the uncinate fasciculus. When differentiating for hCMV infection status, no significant differences were found between CMV+ and CMV-. However, comparing CMV+ against HC, fixel metric reductions were of higher magnitude and of larger spatial extent than in CMV- against HC. Conclusion: Preterm birth can lead to long-lasting alterations of WM micro- and macrostructure, not visible on conventional MRI. Alterations are located predominantly in WM structures associated with cognitive function, likely underlying the cognitive deficits observed in our cohort. These observed structural alterations were more pronounced in preterms who suffered from early postnatal hCMV infection, in line with previous studies suggesting an additive effect.

Clinical Significance of Diffusion Tensor Imaging in Metachromatic Leukodystrophy.

BACKGROUND: Metachromatic leukodystrophy (MLD) is a lysosomal enzyme deficiency disorder leading to progressive demyelination and, consecutively, to cognitive and motor decline. Brain magnetic resonance imaging (MRI) can detect affected white matter as T2 hyperintense areas but cannot quantify the gradual microstructural process of demyelination more accurately. Our study aimed to investigate the value of routine MR diffusion tensor imaging in assessing disease progression. METHODS: MR diffusion parameters (apparent diffusion coefficient [ADC] and fractional anisotropy [FA]) were in the frontal white matter, central region (CR), and posterior limb of the internal capsule in 111 MR datasets from a natural history study of 83 patients (age: 0.5-39.9 years; 35 late-infantile, 45 juvenile, 3 adult, with clinical diffusion sequences of different scanner manufacturers) as well as 120 controls. Results were correlated with clinical parameters reflecting motor and cognitive function. RESULTS: ADC values increase and FA values decrease depending on disease stage/severity. They show region-specific correlations with clinical parameters of motor and cognitive symptoms, respectively. Higher ADC levels in CR at diagnosis predicted a disease course with more rapid motor deterioration in juvenile MLD patients. In highly organized tissues such as the corticospinal tract, in particular, diffusion MR parameters were highly sensitive to MLD-associated changes and did not correlate with the visual quantification of T2 hyperintensities. CONCLUSION: Our results show that diffusion MRI can deliver valuable, robust, clinically meaningful, and easily obtainable/accessible/available parameters in the assessment of prognosis and progression of MLD. Therefore, it provides additional quantifiable information to established methods such as T2 hyperintensity.

Cognitive development after perinatal unilateral infarctions: No evidence for preferential sparing of verbal functions.

BACKGROUND: Even children with extensive perinatal left-sided lesions have been reported to show normal language functions based on right-hemispheric language reorganization. This reorganization can lead to deficits in originary right hemispheric functions ("crowding hypothesis"). In a previous study, however, we identified epilepsy (even when well-controlled), and not language reorganization, as the major risk factor for impaired nonverbal functions. Here, we asked whether verbal and nonverbal functions develop differently, and whether they share the same risk factors. METHODS: We investigated 23 patients (11f, Md = 12.56 years) with perinatal strokes (16 left-sided, 8 with epilepsy), and 23 healthy age-matched controls (8 f, Md = 12.42years). Language functions were assessed using the Potsdam Illinois Test of Psycholinguistic Abilities, nonverbal intelligence with the Test of Nonverbal Intelligence, language lateralization with functional MRI, and lesion size with MRI-based volumetry. RESULTS: We found no systematic difference between verbal and nonverbal skills in our patients or controls [median difference Z(PITPA)-Z(TONI): patients = -0.03, controls = -0.06]. Accordingly, verbal and nonverbal functions were strongly correlated in patients (r = 0.80) and in controls (r = 0.74). Language ability correlated significantly with epilepsy. Furthermore, in patients with epilepsies, verbal skills were significantly lower than in controls. CONCLUSION: In our cohort, we found no evidence for a differential effect of perinatal strokes on the development of verbal versus nonverbal functions, and, specifically, no evidence for a preferential sparing of verbal functions. Epilepsy, even when well-controlled, was confirmed as a single key risk factor for verbal functions.

MRI-based brain volumes of preterm infants at term: a systematic review and meta-analysis.

BACKGROUND: MRI allows a detailed assessment of brain structures in preterm infants, outperforming cranial ultrasound. Neonatal MR-based brain volumes of preterm infants could serve as objective, quantitative and reproducible surrogate parameters of early brain development. To date, there are no reference values for preterm infants' brain volumes at term-equivalent age. OBJECTIVE: Systematic review of the literature to determine reference ranges for MRI-based brain volumes of very preterm infants at term-equivalent age. METHODS: PubMed Database was searched on 6 April 2020 for studies reporting MR-based brain volumes on representative unselected populations of very preterm and/or very low birthweight infants examined at term equivalent age (defined as 37-42 weeks mean postmenstrual age at MRI). Analyses were limited to volumetric parameters reported in >3 studies. Weighted mean volumes and SD were both calculated and simulated for each parameter. RESULTS: An initial 367 publications were identified. Following application of exclusion criteria, 13 studies from eight countries were included for analysis, yielding four parameters. Weighted mean total brain volume was 379 mL (SD 72 mL; based on n=756). Cerebellar volume was 21 mL (6 mL; n=791), cortical grey matter volume 140 mL (47 mL; n=572) and weighted mean volume of unmyelinated white matter was 195 mL (38 mL; n=499). CONCLUSION: This meta-analysis reports pooled data on several brain and cerebellar volumes which can serve as reference for future studies assessing MR-based volumetric parameters as a surrogate outcome for neurodevelopment and for the interpretation of individual or cohort MRI-based volumetric findings.

Non-verbal Intelligence in Unilateral Perinatal Stroke Patients With and Without Epilepsies.

Background: The risk factors for impaired cognitive development after unilateral perinatal stroke are poorly understood. Non-verbal intelligence seems to be at particular risk, since language can shift to the right hemisphere and may thereby reduce the capacity of the right hemisphere for its originary functions. Pharmaco-refractory epilepsies, a frequent complication of perinatal strokes, often lead to impaired intelligence. Yet, the role of well-controlled epilepsies is less well-understood. Here, we investigated whether well-controlled epilepsies, motor impairment, lesion size, lesion side, and lateralization of language functions influence non-verbal functions. Methods: We recruited 8 patients with well-controlled epilepsies (9-26 years), 15 patients without epilepsies (8-23 years), and 23 healthy controls (8-27 years). All underwent the Test of Non-verbal Intelligence, a motor-independent test, which excludes biased results due to motor impairment. Language lateralization was determined with functional MRI, lesion size with MRI-based volumetry, and hand motor impairment with the Jebson-Taylor Hand Function-Test. Results: Patients with epilepsies showed significantly impaired non-verbal intelligence [Md = 89.5, interquartile range (IQR) = 13.5] compared with controls (Md = 103, IQR = 17). In contrast, patients without epilepsies (Md = 97, IQR = 15.0) performed within the range of typically developing children. A multiple regression analysis revealed only epilepsy as a significant risk factor for impaired non-verbal functions. Conclusion: In patients with unilateral perinatal strokes without epilepsies, the neuroplastic potential of one healthy hemisphere is able to support the development of normal non-verbal cognitive abilities, regardless of lesion size, lesion side, or language lateralization. In contrast, epilepsy substantially reduces this neuroplastic potential; even seizure-free patients exhibit below-average non-verbal cognitive functions.

Increased Brain Age Gap Estimate (BrainAGE) in Young Adults After Premature Birth.

Recent evidence suggests increased metabolic and physiologic aging rates in premature-born adults. While the lasting consequences of premature birth on human brain development are known, its impact on brain aging remains unclear. We addressed the question of whether premature birth impacts brain age gap estimates (BrainAGE) using an accurate and robust machine-learning framework based on structural MRI in a large cohort of young premature-born adults (n = 101) and full-term (FT) controls (n = 111). Study participants are part of a geographically defined population study of premature-born individuals, which have been followed longitudinally from birth until young adulthood. We investigated the association between BrainAGE scores and perinatal variables as well as with outcomes of physical (total intracranial volume, TIV) and cognitive development (full-scale IQ, FS-IQ). We found increased BrainAGE in premature-born adults [median (interquartile range) = 1.4 (-1.3-4.7 years)] compared to full-term controls (p = 0.002, Cohen's d = 0.443), which was associated with low Gestational age (GA), low birth weight (BW), and increased neonatal treatment intensity but not with TIV or FS-IQ. In conclusion, results demonstrate elevated BrainAGE in premature-born adults, suggesting an increased risk for accelerated brain aging in human prematurity.

A multidimensional artefact-reduction approach to increase robustness of first-level fMRI analyses: Censoring vs. interpolating.

BACKGROUND: This manuscript describes a new, multidimensional and data-driven approach to identify outlying datapoints from a first-level fMRI dataset. NEW METHOD: Using three different indicators of data corruption (the fast variance component of DVARS [Δ%D-var], scan-to-scan total displacement [STS], and each scan's overall explained variance [R2]), it identifies outlying datapoints while being balanced using Akaike'c corrected criterion (AIC C) to avoid overcorrection. We then explore the impact of censoring, interpolating, or both, to remove a bad scan's contribution to the final timeseries. RESULTS AND COMPARISON WITH EXISTING METHODS: Our results (using three real-life datasets and extensive simulations) show that motion-corrupted datapoints as well as non-motion related image artefacts are detected reliably. Using several indicators is shown to be an advantage over existing single-indicator solutions in different settings. As a result of using our algorithm, stronger activation (as detected by both T-value and number of activated voxels) and an increase in the temporal signal-to-noise ratio can be seen. The effects of censoring and interpolation are distinct and complex. CONCLUSIONS: The multidimensional approach described here is able to identify outlying datapoints in fMRI timeseries, with demonstrable positive effects on several outcome measures. While censoring datapoints may be preferable in many settings, the ultimate choice on which approach to choose may depend on the data at hand. Recommendations are provided for different scenarios.

Clinical application of advanced MR methods in children: points to consider.

The application of both functional MRI and diffusion MR tractography prior to a neurosurgical operation is well established in adults, but less so in children, for several reasons. For this review, we have identified several aspects (task design, subject preparation, actual scanning session, data processing, interpretation of results, and decision-making) where pediatric peculiarities should be taken into account. Further, we not only systematically identify common issues, but also provide solutions, based on our experience as well as a review of the pertinent literature. The aim is to provide the clinician as well as the imaging scientist with information that helps to plan, conduct, and interpret such a clinically-indicated exam in a way that maximizes benefit for, and minimizes the burden on the individual child.

Role of presurgical functional MRI and diffusion MR tractography in pediatric low-grade brain tumor surgery: a single-center study.

PURPOSE: Presurgical functional MRI (fMRI) and diffusion MRI tractography (dMRI tractography) are widely employed to delineate eloquent brain regions and their connections prior to brain tumor resection in adults. However, such studies are harder to perform in children, resulting in suboptimal neurosurgical care in pediatric brain tumor surgery as compared to adults. Thus, our objective was to assess the feasibility and the influence of presurgical advanced MR imaging on neurosurgical care in pediatric brain tumor surgery. METHODS: Retrospective analyses of 31 presurgical fMRI/dMRI tractography studies were performed in children with low-grade tumors near eloquent brain regions at our site between 2005 and 2017. RESULTS: In only 3/31 cases, imaging results were not interpretable (10%). All 28 successful imaging sessions were used for neurosurgical risk assessment. Based on this, surgery was canceled in 2/28 patients, and intention to treat was changed in 5/28 patients. In 4/28 cases, the surgical approach was changed and in 10/28, electrode placement for intraoperative neurophysiological monitoring was guided by imaging results. Gross total resection (GTR) was planned in 21/28 cases and could be achieved in 15/21 (71%). Despite highly eloquent tumor location, only four children suffered from a mild permanent neurological deficit after the operation. CONCLUSIONS: We demonstrate that presurgical fMRI/dMRI tractography can have a profound impact on pediatric brain tumor management, optimizing preoperative risk-assessment and pre- as well as intraoperative decision-making. We believe that these tools should be offered to children suffering from eloquent brain tumors as part of a comprehensive operative work-up.

Assessing motor, visual and language function using a single 5-minute fMRI paradigm: three birds with one stone.

Clinical functional Magnetic Resonance Imaging (fMRI) requires inferences on localization of major brain functions at the individual subject level. We hypothesized that a single "triple use" task would satisfy sensitivity and reliability requirements for successfully assessing the motor, visual and language domain in this context. This was tested here by the application in a group of healthy adults, assessing sensitivity and reliability at the individual subject level, separately for each domain.Our "triple use" task consisted of 2 conditions (condition 1, assessing motor and visual domain, and condition 2, assessing the language domain), serving mutually as active/control. We included 20 healthy adult subjects. Random effect analyses showed activation in primary motor, visual and language regions, as expected. Less expected regions were activated both for the motor and visual domains. Further, reliability of primary activation patterns was very high across individual subjects, with activation seen in 70-100% of subjects in primary motor, visual, and left-lateralized language regions.These findings suggest the "triple use" task to be reliable at the individual subject's level to assess motor, visual and language domains in the clinical fMRI context. Benefits of such an approach include shortening of acquisition time, simplicity of the task for each domain, and using a visual stimulus. Following establishment of reliability in adults, the task may also be a valuable addition in the pediatric clinical fMRI context, where each of these factors is of high relevance.

A spline-based regression parameter set for creating customized DARTEL MRI brain templates from infancy to old age.

This dataset contains the regression parameters derived by analyzing segmented brain MRI images (gray matter and white matter) from a large population of healthy subjects, using a multivariate adaptive regression splines approach. A total of 1919 MRI datasets ranging in age from 1-75 years from four publicly available datasets (NIH, C-MIND, fCONN, and IXI) were segmented using the CAT12 segmentation framework, writing out gray matter and white matter images normalized using an affine-only spatial normalization approach. These images were then subjected to a six-step DARTEL procedure, employing an iterative non-linear registration approach and yielding increasingly crisp intermediate images. The resulting six datasets per tissue class were then analyzed using multivariate adaptive regression splines, using the CerebroMatic toolbox. This approach allows for flexibly modelling smoothly varying trajectories while taking into account demographic (age, gender) as well as technical (field strength, data quality) predictors. The resulting regression parameters described here can be used to generate matched DARTEL or SHOOT templates for a given population under study, from infancy to old age. The dataset and the algorithm used to generate it are publicly available at https://irc.cchmc.org/software/cerebromatic.php.

Regional Gray Matter Volume Differences Between Adolescents With ADHD and Typically Developing Controls: Further Evidence for Anterior Cingulate Involvement.

OBJECTIVE: The present study investigated structural brain differences between adolescents with ADHD and matched control participants. METHOD: Voxel-based morphometry (VBM) using the DARTEL approach was performed to assess regional gray matter (GM) volumes. Additionally, individual performance on tests of attention was recorded to correlate ADHD related cognitive impairments with regional gray matter abnormalities. RESULTS: We found significantly smaller GM volume in subjects with ADHD compared to their matched controls within the anterior cingulate cortex (ACC), the occipital cortex, bilateral hippocampus/amygdala and in widespread cerebellar regions. Further, reductions of the ACC gray matter volume were found to correlate with scores of selective inattention. CONCLUSION: These findings underline that structural alterations in a widespread cortico-subcortical network seem to underlie the observable attention problems in patients with ADHD.

Demyelination load as predictor for disease progression in juvenile metachromatic leukodystrophy.

OBJECTIVE: The aim of this study was to investigate whether the extent and topography of cerebral demyelination correlates with and predicts disease progression in patients with juvenile metachromatic leukodystrophy (MLD). METHODS: A total of 137 MRIs of 46 patients with juvenile MLD were analyzed. Demyelination load and brain volume were quantified using the previously developed Software "clusterize." Clinical data were collected within the German Leukodystrophy Network and included full scale intelligence quotient (FSIQ) and gross motor function data. Voxel-based lesion-symptom mapping (VLSM) across the whole brain was performed to investigate the spatial relationship of cerebral demyelination with motor or cognitive function. The prognostic value of the demyelination load at disease onset was assessed to determine the severity of disease progression. RESULTS: The demyelination load (corrected by the individual brain volume) correlated significantly with gross motor function (r = +0.55) and FSIQ (r = -0.55). Demyelination load at disease onset was associated with the severity of disease progression later on (P < 0.01). VLSM results associated frontal lobe demyelination with loss in FSIQ and more central region demyelination with decline of motor function. Especially progression of demyelination within the motor area was associated with severe disease progression. INTERPRETATION: We were able to show for the first time in a large cohort of patients with juvenile MLD that the demyelination load correlates with motor and cognitive symptoms. Moreover, demyelination load at disease onset, especially the involvement of the central region, predicts severity of disease progression. Thus, demyelination load seems a functionally relevant MRI parameter.

Lesion characteristics driving right-hemispheric language reorganization in congenital left-hemispheric brain damage.

Pre- or perinatally acquired ("congenital") left-hemispheric brain lesions can be compensated for by reorganizing language into homotopic brain regions in the right hemisphere. Language comprehension may be hemispherically dissociated from language production. We investigated the lesion characteristics driving inter-hemispheric reorganization of language comprehension and language production in 19 patients (7-32years; eight females) with congenital left-hemispheric brain lesions (periventricular lesions [n=11] and middle cerebral artery infarctions [n=8]) by fMRI. 16/17 patients demonstrated reorganized language production, while 7/19 patients had reorganized language comprehension. Lesions to the insular cortex and the temporo-parietal junction (predominantly supramarginal gyrus) were significantly more common in patients in whom both, language production and comprehension were reorganized. These areas belong to the dorsal stream of the language network, participating in the auditory-motor integration of language. Our data suggest that the integrity of this stream might be crucial for a normal left-lateralized language development.

CerebroMatic: A Versatile Toolbox for Spline-Based MRI Template Creation.

Brain image spatial normalization and tissue segmentation rely on prior tissue probability maps. Appropriately selecting these tissue maps becomes particularly important when investigating "unusual" populations, such as young children or elderly subjects. When creating such priors, the disadvantage of applying more deformation must be weighed against the benefit of achieving a crisper image. We have previously suggested that statistically modeling demographic variables, instead of simply averaging images, is advantageous. Both aspects (more vs. less deformation and modeling vs. averaging) were explored here. We used imaging data from 1914 subjects, aged 13 months to 75 years, and employed multivariate adaptive regression splines to model the effects of age, field strength, gender, and data quality. Within the spm/cat12 framework, we compared an affine-only with a low- and a high-dimensional warping approach. As expected, more deformation on the individual level results in lower group dissimilarity. Consequently, effects of age in particular are less apparent in the resulting tissue maps when using a more extensive deformation scheme. Using statistically-described parameters, high-quality tissue probability maps could be generated for the whole age range; they are consistently closer to a gold standard than conventionally-generated priors based on 25, 50, or 100 subjects. Distinct effects of field strength, gender, and data quality were seen. We conclude that an extensive matching for generating tissue priors may model much of the variability inherent in the dataset which is then not contained in the resulting priors. Further, the statistical description of relevant parameters (using regression splines) allows for the generation of high-quality tissue probability maps while controlling for known confounds. The resulting CerebroMatic toolbox is available for download at http://irc.cchmc.org/software/cerebromatic.php.

Plasticity during Early Brain Development Is Determined by Ontogenetic Potential.

Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building.