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.

Processing speed and its association with working memory and episodic memory 3-6 months after pediatric mild traumatic brain injury.

OBJECTIVE: Following mild traumatic brain injury (mTBI), children show reduced processing speed (PS). Evidence suggests that slowed PS after TBI is associated with working memory deficits. Our aim was to investigate several forms of PS and to examine its impact on working and episodic memory performance in children after mTBI. METHOD: We included data of 64 children after mTBI and 57 healthy control children aged 8-16 years. PS (Color Naming, Coding, Symbol Search, Alertness) was compared between groups 1 week (T1) and 3-6 months (T2) after the injury; working and episodic memory outcome was compared between groups at T2. RESULTS: Alertness at T1 and Color Naming at T1 and T2 were significantly reduced following mTBI compared to controls, although most group differences in PS disappeared when patients with previous impairments and mTBI were excluded. PS was predictive for episodic and working memory performance 3-6 months after injury, whereas group was a significant predictor of working memory. CONCLUSIONS: Compared to healthy controls, children after mTBI showed reduced performance in verbal PS, which was associated with working memory. In children who are symptomatic after mTBI, diagnostic screening of PS could be helpful in identifying patients that could profit from speed-improving strategies.

Enhancing the Follow-up Assessment of Very Preterm Children with Regard to 5-Year IQ Considering Socioeconomic Status.

BACKGROUND: Specifying peri- and postnatal factors in children born very preterm (VPT) that affect later outcome helps to improve long-term treatment. AIM: To enhance the predictability of 5-year cognitive outcome by perinatal, 2-year developmental and socio-economic data. SUBJECTS AND OUTCOME MEASURES: 92 VPT infants, born 2007-2009, gestational age<32 weeks and/or birthweight of 1500 g, were assessed longitudinally including basic neonatal, socio-economic (SES), 2-year Mental Developmental Index (MDI, Bayley Scales II), 5-year Mental Processing Composite (MPC, Kaufman-Assessment Battery for Children), and Language Screening for Preschoolers data. 5-year infants born VPT were compared to 34 term controls. RESULTS: The IQ of 5-year infants born VPT was 10 points lower than that of term controls and influenced independently by preterm birth and SES. MDI, SES, birth weight and birth complications explained 48% of the variance of the MPC. The MDI proved highly predictive (r=0.6, R2=36%) for MPC but tended to underestimate the cognitive outcome. A total of 61% of the 2-year infants born VPT were already correctly classified (specificity of .93, sensitivity of .54). CHAID decision tree technique identified SES as decisive for the outcome for infants born VPT with medium MDI results (76-91): They benefit from effects associated to a higher SES, while those with a poor MDI outcome and a birth weight≤890 g do not. CONCLUSION: Developmental follow-up of preterm children enhances the quality of prognosis and later outcome when differentially considering perinatal risks and SES.

Health-Related Quality of Life in Young Adults Following Pediatric Arterial Ischemic Stroke.

Background and Purpose- Pediatric arterial ischemic stroke (AIS) is a rare disease leading to long-lasting neurological sequelae. Little is known about the long-term health-related quality of life (HRQoL) of these patients. The study aims to compare HRQoL in young adults who have had pediatric AIS with a healthy control group. Methods- A cross-sectional study compared self-rated HRQoL, depression, fatigability, and behavior in pediatric stroke survivors to healthy controls. Patients with a confirmed diagnosis of pediatric AIS who were ≥18 years at the time of recruitment and ≥2 years after acute AIS, as well as healthy controls ≥18 years matched for age, sex, and socioeconomic status were included. Primary outcome was HRQoL measured with the Short Form Health Survey. Results- Thirty-three patients (median [interquartile range] aged 22 years [20-26]; 22 males, 67%) and 71 controls (median [interquartile range] aged 23 years [21-25]; 41 males, 58%) were included. Overall, HRQoL, depression, or fatigability did not differ between the patients and the control group. Patients rated themselves lower on the disinhibition scale (P=0.049) and tended to rate themselves lower on the executive dysfunction scale (P=0.076). Patients with a poor outcome 24 months after AIS showed a clear trend toward impairment of executive functioning (P=0.056) and work/productivity in the stroke-specific QoL (P=0.05). Conclusions- Self-rated HRQoL, depression, and fatigability in adult pediatric stroke survivors are comparable to healthy adult peers. A poor outcome 24 months after acute stroke might affect work performance and executive functioning in adulthood.

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.

A "one size fits all" approach to language fMRI: increasing specificity and applicability by adding a self-paced component.

We have previously established an fMRI task battery suitable for mapping the language processing network in children. Among the tasks used, the synonyms and the vowel identification task induced robust task-related activations in children with average language abilities; however, the fixed presentation time seems to be a drawback in participants with above- or below-average language abilities. This feasibility study in healthy adults (n = 20) was aimed at adapting these tasks to the individual level of each patient by implementing a self-paced stimulus presentation. The impact of using a block- versus an event-related statistical approach was also evaluated. The self-paced modification allowed our participants with above-average language abilities to process stimuli much faster than originally implemented, likely increasing task adherence. A higher specificity of the event-related analysis was confirmed by stronger left inferior frontal and crossed cerebellar activations. We suggest that self-paced paradigms and event-related analyses may both increase specificity and applicability.

German Validation of the Conners 3® Rating Scales for Parents, Teachers, and Children.

Objective: Attention-deficit/hyperactivity disorder (ADHD) rating scales such as the Conners' Rating Scales (CRS) are valuable adjuncts for diagnosis, since they offer parent, teacher, and self-ratings of children susceptible for ADHD. Even though the scales are widely used internationally, cross-cultural comparability has rarely been verified, and culture and language invariance have only been presumed. The Conners 3(®) rating scales are the updated version of the CRS, though hardly any studies report the psychometric properties apart from the results published in the test edition itself. To our knowledge there are no studies on the various adaptations of the Conners 3(®) in other languages. Method: The German translations of the Conners 3(®) were completed by 745 children, 953 parents, and 741 teachers (children's age range: 6­18 years, mean: 11.74 years of age). Exploratory and confirmatory factor analyses on content scale items were conducted to obtain the factor structure for the German version and to replicate the factor structure of the original American models. Cronbach's α was calculated to establish internal consistency. Results: The exploratory analyses for the German model resulted in factor structures globally different from the American model, though confirmatory analyses revealed very good model fi ts with highly satisfying Cronbach's αs. We were able to provide empirical evidence for the subscale Inattention which had only hypothetically been derived by Conners (2008). Conclusions: Even though the exploratory analyses resulted in different factor structures, the confirmatory analyses have such excellent psychometric properties that use of the German adaptation of the Conners 3(®) is justifi ed in international multicenter studies.

Postnatal human cytomegalovirus infection in preterm infants has long-term neuropsychological sequelae.

OBJECTIVE: To evaluate whether an early postnatal infection poses a long-term risk for neuropsychological impairment to neonates born very prematurely. STUDY DESIGN: Adolescents born very preterm (n = 42, 11.6-16.2 years, mean = 13.9; 15 girls; 19 with and 23 without an early postnatal human cytomegalovirus [CMV] infection) and typically developing, term born controls (n = 24, 11.3-16.6 years, mean = 13.6; 12 girls) were neuropsychologically assessed with the German version of the Wechsler Intelligence Scale and the Developmental Test for Visual Perception. RESULTS: As expected, the full cohort of adolescents born preterm had significantly lower scores than term born controls on IQ (preterm: mean [SD] = 98.43 [14.83], control: 110.00 [8.10], P = .015) and on visuoperceptive abilities (95.64 [12.87] vs 106.24 [9.95], P = .016). Furthermore, adolescents born preterm with early postnatal CMV infection scored significantly lower than those without this infection regarding overall cognitive abilities (92.67 [14.71] vs 102.75 [13.67], P = .030), but not visuoperceptive abilities (91.22 [10.88] vs 98.96 [13.45], P > .05). CONCLUSIONS: In our small but well-characterized group, our results provide evidence for adverse effects of early postnatal CMV infection on overall cognitive functions in adolescents born preterm. If confirmed, these results support the implementation of preventive measures.

Visual-perceptual impairment in children with cerebral palsy: a systematic review.

AIM: Visual perception is one of the cognitive functions often impaired in children with cerebral palsy (CP). The aim of this systematic literature review was to assess the frequency of visual-perceptual impairment (VPI) and its relationship with patient characteristics. METHOD: Eligible studies were relevant papers assessing visual perception with five common standardized assessment instruments in children with CP published from January 1990 to August 2011. RESULTS: Of the 84 studies selected, 15 were retained. In children with CP, the proportion of VPI ranged from 40% to 50% and the mean visual perception quotient from 70 to 90. None of the studies reported a significant influence of CP subtype, IQ level, side of motor impairment, neuro-ophthalmological outcomes, or seizures. The severity of neuroradiological lesions seemed associated with VPI. The influence of prematurity was controversial, but a lower gestational age was more often associated with lower visual motor skills than with decreased visual-perceptual abilities. INTERPRETATION: The impairment of visual perception in children with CP should be considered a core disorder within the CP syndrome. Further research, including a more systematic approach to neuropsychological testing, is needed to explore the specific impact of CP subgroups and of neuroradiological features on visual-perceptual development.

Specific impairment of functional connectivity between language regions in former early preterms.

Very preterm (PT) birth (≤32 weeks of gestation) carries a high risk for an adverse neurodevelopmental outcome. In recent years, the importance of neurocognitive deficits in the language domain has been increasingly recognized, which can be well-characterized using neuropsychological testing and noninvasive imaging approaches. We compared former early PT born children and adolescents (PT, n = 29, 20M) and typically developing children (TD, n = 19, 7M), using conventional fMRI group analyses as well as functional connectivity analyses. We found only small regions with significantly different group activation (PT > TD) but significantly stronger connectivity between superior temporal lobe (STL) language regions in TD participants. There were also significant differences in local and global network efficiency (TD > PT). Surprisingly, there was a stronger connectivity of STL regions with non-STL regions both intrahemispherically and interhemispherically in PT participants, suggesting the coexistence of reduced and increased connectivity in the language network of former PTs. Very similar results were obtained when using task-based versus resting state functional connectivity approaches. Finally, lateralization of functional connectivity correlated with verbal comprehension abilities, suggesting that a more bilateral language comprehension representation is associated with better performance. Our results underline the importance of interhemispheric crosstalk for language comprehension.

Long-term neurobiological consequences of early postnatal hCMV-infection in former preterms: a functional MRI study.

Early postnatal infection with human cytomegalovirus (hCMV) may contribute to an adverse cognitive outcome in early preterm-born children (PT). We here set out to explore whether long-term neurobiological consequences of such an infection are detectable using fMRI in children and adolescents who were born very preterm and who either did (PThCMV+ ) or did not (PT(hCMV-)) suffer from an early postnatal hCMV-infection, when compared with typically developing healthy control (HC) subjects. Overall, data from 71 children and adolescents could be included, 34 PT (of which 15 were PT(hCMV+) and 19 were PT(hCMV-)) and 37 HC. Using a recently established "dual use" fMRI task, we investigated language and visuospatial functions. There were significant activation differences in the left hippocampus (PT > HC and PT(hCMV+) > HC), and in the right anterior cingulate cortex (PT(hCMV-) > PT(hCMV+)) when performing the language task. Surprisingly, only a small region in the occipital cortex showed a significant activation difference (HC > PT(HCMV-)) when performing the visuospatial task. Targeted analyses revealed differences in gray matter volume, but not density, in several brain regions. Our results suggest that long-term neurobiological consequences of an early postnatal hCMV infection are detectable even in older children and adolescents formerly born very preterm, compatible with a higher effort when performing a cognitive task. This suggests that measures to prevent such an infection are warranted. Furthermore, an interrelation of brain structure and function was detected that may constitute a severe confound when using fMRI to compare structurally differing groups.

Pharmacotherapy of attention deficit in neurofibromatosis type 1: effects on cognition.

AIM: Attention deficit with or without hyperactivity (AD[H]D) is a common comorbidity of neurofibromatosis type 1 (NF 1). We tested the hypothesis that permanent medication with methylphenidate can improve cognitive functioning in children with NF 1 and comorbid AD(H)D. PATIENTS AND METHOD: We retrospectively analyzed data of a clinical sample of patients with NF 1 with or without AD(H)D, who underwent standardized neuropsychological diagnostics twice (age range: T1, 6-14 years; T2, 7-16 years; mean interval, 49.09 months). A total of 16 children without AD(H)D (nine females) were compared with 14 unmedicated children with AD(H)D (eight females) and to 13 medicated children with AD(H)D (two females). Effects of medication and attention on cognitive outcome (IQ) were tested by repeated measures analysis of covariance (rmANCOVA). RESULTS: Medicated children with NF 1 improved significantly in full-scale IQ from T1 to T2 (IQ[T1] = 80.38, IQ[T2] = 98.38, confidence interval [diff]: -25.59 to -10.40, p < 0.0001), this effect was not evident for the other groups. With attention measures as covariates, the effect remained marginally significant. CONCLUSION: Children and adolescents with NF 1 and comorbid AD(H)D may profit from MPH medication regarding general cognition. This effect could be specific for the group of patients with NF 1, and cannot be explained solely by improvements in attention. Controlled, prospective studies are warranted to corroborate our findings.

Impaired episodic verbal memory recall after 1 week and elevated forgetting in children after mild traumatic brain injury - results from a short-term longitudinal study.

Objective: There is preliminary evidence that children after traumatic brain injury (TBI) have accelerated long-term forgetting (ALF), i.e., an adequate learning and memory performance in standardized memory tests, but an excessive rate of forgetting over delays of days or weeks. The main aim of this study was to investigate episodic memory performance, including delayed retrieval 1 week after learning, in children after mild TBI (mTBI). Methods: This prospective study with two time-points (T1: 1 week after injury and T2: 3-6 months after injury), included data of 64 children after mTBI and 57 healthy control children aged between 8 and 16 years. We assessed episodic learning and memory using an auditory word learning test and compared executive functions (interference control, working memory, semantic fluency and flexibility) and divided attention between groups. We explored correlations between memory performance and executive functions. Furthermore, we examined predictive factors for delayed memory retrieval 1 week after learning as well as for forgetting over time. Results: Compared to healthy controls, patients showed an impaired delayed recall and recognition performance 3-6 months after injury. Executive functions, but not divided attention, were reduced in children after mTBI. Furthermore, parents rated episodic memory as impaired 3-6 months after injury. Additionally, verbal learning and group, but not executive functions, were predictive for delayed recall performance at both time-points, whereas forgetting was predicted by group. Discussion: Delayed recall and forgetting over time were significantly different between groups, both post-acutely and in the chronic phase after pediatric mTBI, even in a very mildly injured patient sample. Delayed memory performance should be included in clinical evaluations of episodic memory and further research is needed to understand the mechanisms of ALF.

Different trajectories of post-concussive symptom subscales after pediatric mild traumatic brain injury: Data from a prospective longitudinal study.

PURPOSE: The aim of this study was to investigate the trajectory of parent-rated post-concussive symptoms (PCS), attentional performance and participation within 6 months in children after mild traumatic brain injury (mTBI). METHODS: For this prospective longitudinal study, we included data on 64 children after mTBI and 57 healthy control children (age 8-16 years). Parents rated PCS using the Post-Concussion Symptom Inventory (PCSI) immediately (T0), 1 week (T1), and 3-6 months after injury (T2). Attentional performance (alertness, selective and divided attention) was measured using the Test of Attentional Performance (TAP) at T1 and T2 and participation was measured using the Child and Adolescent Scale of Participation (CASP) at T2. RESULTS: Friedman tests showed different trajectories of PCS subscales over time: Compared to pre-injury level, the amount of somatic and cognitive PCS was still elevated at T1, while emotional PCS at T1 were already comparable to pre-injury level. The rating of sleep-related PCS at T2 was significantly elevated compared to the pre-injury rating. Quade ANCOVAs indicated group differences in PCS subscales between patients and controls at T1, but not at T2. Patients and controls showed a similar performance in tests of attention at T1 and T2, but parental rating of participation at school was significantly reduced. Although cognitive PCS and attention were not correlated, there were significantly negative Spearman correlations between participation at home and pre-injury and concurrent PCS at T2. CONCLUSIONS: Our data imply that sleep-related PCS are still elevated weeks after injury and are thus a target for interventions after mTBI.

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.

Long-term forgetting is independent of age in healthy children and adolescents.

Introduction: In clinical neuropsychology, the phenomenon of accelerated long-term forgetting (ALF) has advanced to be a marker for subtle but clinically relevant memory problems associated with a range of neurological conditions. The normal developmental trajectory of long-term memory, in this case, memory recall after 1 week, and the influence of cognitive variables such as intelligence have not extensively been described, which is a drawback for the use of accelerated long-term forgetting measures in pediatric neuropsychology. Methods: In this clinical observation study, we analyzed the normal developmental trajectory of verbal memory recall after 1 week in healthy children and adolescents. We hypothesized that 1-week recall and 1-week forgetting would be age-dependent and correlate with other cognitive functions such as intelligence and working memory. Sixty-three healthy participants between the ages of 8 and 16 years completed a newly developed auditory verbal learning test (WoMBAT) and the WISC-V intelligence test (General Ability Index, GAI). Using these tests, 1 week recall and 1 week forgetting have been studied in relation to GAI, verbal learning performance, and verbal working memory. Results: Neither 1-week recall nor 1-week forgetting seems to be age-dependent. They are also not significantly predicted by other cognitive functions such as GAI or working memory. Instead, the ability to recall a previously memorized word list after 7 days seems to depend solely on the initial learning capacity. Conclusion: In the clinical setting, this finding can help interpret difficulties in free recall after 7 days or more since they can probably not be attributed to young age or low intelligence.

Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders causing learning disabilities by mutations in the neurofibromin gene, an important inhibitor of the RAS pathway. In a mouse model of NF1, a loss of function mutation of the neurofibromin gene resulted in increased gamma aminobutyric acid (GABA)-mediated inhibition which led to decreased synaptic plasticity and deficits in attentional performance. Most importantly, these defictis were normalized by lovastatin. This placebo-controlled, double blind, randomized study aimed to investigate synaptic plasticity and cognition in humans with NF1 and tried to answer the question whether potential deficits may be rescued by lovastatin. METHODS: In NF1 patients (n = 11; 19-44 years) and healthy controls (HC; n = 11; 19-31 years) paired pulse transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (paired pulse) and synaptic plasticity (paired associative stimulation). On behavioural level the Test of Attentional Performance (TAP) was used. To study the effect of 200 mg lovastatin for 4 days on all these parameters, a placebo-controlled, double blind, randomized trial was performed. RESULTS: In patients with NF1, lovastatin revealed significant decrease of intracortical inhibition, significant increase of synaptic plasticity as well as significant increase of phasic alertness. Compared to HC, patients with NF1 exposed increased intracortical inhibition, impaired synaptic plasticity and deficits in phasic alertness. CONCLUSIONS: This study demonstrates, for the first time, a link between a pathological RAS pathway activity, intracortical inhibition and impaired synaptic plasticity and its rescue by lovastatin in humans. Our findings revealed mechanisms of attention disorders in humans with NF1 and support the idea of a potential clinical benefit of lovastatin as a therapeutic option.

Delayed episodic memory recall after one week is associated with executive functions and divided attention in pediatric epilepsy patients.

AIM: Recent studies suggest that although children with epilepsy may show normal learning and memory performance, accelerated long-term forgetting (ALF) may become evident over time. Our study examined associations between delayed episodic memory performance (recall 1-week after learning) and executive functions. METHOD: A consecutive sample of children with a diagnosis of idiopathic epilepsy with focal or generalized seizures, without morphologic or metabolic abnormalities (n = 20, mean age: 11.70 years) was compared to an IQ-matched healthy control group (n = 20, mean age: 11.55 years). We also assessed parents' and children's rating of forgetting in everyday life and explored its association with delayed episodic memory recall. RESULTS: Similar to results from recent studies of pediatric patients with temporal lobe epilepsy or genetic generalized epilepsy, our pediatric epilepsy patients showed a significantly elevated recall loss over time, although verbal learning, immediate and 30-minute recall was comparable to the matched control group. Additionally, delayed memory recall in patients was moderately associated with their subjective rating of forgetting, as well as with executive functions (verbal fluency and switching) and divided attention. INTERPRETATION: We assume that executive functions play a crucial role in deep memory encoding, facilitating stronger and more enduring memory traces. Given that approximately 20% of epilepsy patients - compared to a healthy reference sample - had a significantly reduced delayed recall and due to the clinical relevance of long-term memory, age-appropriate standard norms for free memory recall after 1-week are desirable.

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.

Functional MRI-guided probabilistic tractography of cortico-cortical and cortico-subcortical language networks in children.

In this study, we analyzed the structural connectivity of cortico-cortical and cortico-subcortical language networks in healthy children, using probabilistic tractography based on high angular resolution diffusion imaging. In addition to anatomically defining seed and target regions for tractography, we used fMRI to target inferior frontal and superior temporal cortical language areas on an individual basis. Further, connectivity between these cortical and subcortical (thalamus, caudate nucleus) language regions was assessed. Overall, data from 15 children (8f) aged 8-17 years (mean age 12.1 ±3 years) could be included. A slight but non-significant trend towards leftward lateralization was found in the arcuate fasciculus/superior longitudinal fasciculus (AF/SLF) using anatomically defined masks (p>.05, Wilcoxon rank test), while the functionally-guided tractography showed a significant lateralization to the left (p<.01). Connectivity of the thalamus with language regions was strong but not lateralized. Connectivity of the caudate nucleus with inferior-frontal language regions was also symmetrical, while connectivity with superior-temporal language regions was strongly lateralized to the left (p<.01). To conclude, we could show that tracking the arcuate fasciculus/superior longitudinal fasciculus is possible using both anatomically and functionally-defined seed and target regions. With the latter approach, we could confirm the presence of structurally-lateralized cortico-cortical language networks already in children, and finally, we could demonstrate a strongly asymmetrical connectivity of the caudate nucleus with superior temporal language regions. Further research is necessary in order to assess the usability of such an approach to assess language dominance in children unable to participate in an active fMRI study.