Pulmonary vein narrowing after pulsed field versus thermal ablation.

AIMS: When it occurs, pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is associated with significant morbidity. Even mild-to-moderate PV narrowing may have long-term implications. Unlike thermal ablation energies, such as radiofrequency (RF) or cryothermy, pulsed field ablation (PFA) is a non-thermal modality associated with less fibrotic proliferation. Herein, we compared the effects of PFA vs. thermal ablation on PV narrowing after AF ablation. METHODS AND RESULTS: ADVENT was a multi-centre, randomized, single-blind study comparing PFA (pentaspline catheter) with thermal ablation-force-sensing RF or cryoballoon (CB)-to treat drug-refractory paroxysmal AF. Pulmonary vein diameter and aggregate cross-sectional area were obtained by baseline and 3-month imaging. The pre-specified, formally tested, secondary safety endpoint compared a measure of PV narrowing between PFA vs. thermal groups, with superiority defined by posterior probability > 0.975. Among subjects randomized to PFA (n = 305) or thermal ablation (n = 302), 259 PFA and 255 thermal ablation (137 RF and 118 CB) subjects had complete baseline and 3-month PV imaging. No subject had significant (≥70%) PV stenosis. Change in aggregate PV cross-sectional area was less with PFA (-0.9%) than thermal ablation (-12%, posterior probability > 0.999)-primarily driven by the RF sub-cohort (-19.5%) vs. CB sub-cohort (-3.3%). Almost half of all PFA PV diameters did not decrease, but the majority (80%) of RF PVs decreased, regardless of PV anatomic location. CONCLUSION: In this first randomized comparison of PFA vs. thermal ablation, PFA resulted in less PV narrowing-thereby underscoring the qualitatively differential and favourable impact of PFA on PV tissue.

A greater modulation of the visual and fronto-parietal networks for children in a post-media versus pre-media exposure group.

AIM: Media use in children has exploded in the past several decades, most recently fuelled by portable electronic devices. This study aims to explore differences in functional brain connectivity in children during a story-listening functional MRI (fMRI) task using data collected before (1998) and after (2013) the widespread adoption of media. METHODS: Cross-sectional data were collected from English-speaking 5- to 7-year-old children at Cincinnati Children's Hospital Medical Center, USA, of a functional MRI narrative comprehension task completed in 1998 (n = 22) or 2013 (n = 25). Imaging data were processed using a graph theory approach, focusing on executive functions, language and visual processing networks supporting reading. RESULTS: Group differences suggest more efficient processing in the fronto-parietal network in the pre-media group while listening to stories. A modulation of the visual and fronto-parietal networks for the post-media exposure group was found. CONCLUSION: Further studies are needed to assess effects over time in the more exposed group to discern a causal effect of portable devices on cognitive networks.

The role of visual attention in dyslexia: Behavioral and neurobiological evidence.

Poor phonological processing has typically been considered the main cause of dyslexia. However, visuo-attentional processing abnormalities have been described as well. The goal of the present study was to determine the involvement of visual attention during fluent reading in children with dyslexia and typical readers. Here, 75 children (8-12 years old; 36 typical readers, 39 children with dyslexia) completed cognitive and reading assessments. Neuroimaging data were acquired while children performed a fluent reading task with (a) a condition where the text remained on the screen (Still) versus (b) a condition in which the letters were being deleted (Deleted). Cognitive assessment data analysis revealed that visual attention, executive functions, and phonological awareness significantly contributed to reading comprehension in both groups. A seed-to-voxel functional connectivity analysis was performed on the fluency functional magnetic resonance imaging task. Typical readers showed greater functional connectivity between the dorsal attention network and the left angular gyrus while performing the Still and Deleted reading tasks versus children with dyslexia. Higher connectivity values were associated with higher reading comprehension. The control group showed increased functional connectivity between the ventral attention network and the fronto-parietal network during the Deleted text condition (compared with the Still condition). Children with dyslexia did not display this pattern. The results suggest that the synchronized activity of executive, visual attention, and reading-related networks is a pattern of functional integration which children with dyslexia fail to achieve. The present evidence points toward a critical role of visual attention in dyslexia.

Maternal depression is associated with decreased functional connectivity within semantics and phonology networks in preschool children.

INTRODUCTION: Maternal depression is characterized by a lack of emotional responsiveness and engagement with their child, which may lead to the child's decreased cognitive, and language outcomes all related to the child's future reading outcomes. The relations between maternal depression and functional connectivity in neural circuits supporting language in the child was explored. METHODS: Eleven 4-year-old girls completed language abilities assessment and resting-state functional magnetic resonance imaging scan. Their mothers completed the Beck's Depression Inventory (BDI) to examine maternal depression when the child was 12 months old and at the age of 4. Functional connections within the child's resting-state phonology, semantics, language networks were correlated with maternal BDI scores at the age of 4 years. RESULTS: Higher maternal depression was associated with the child's decreased within the semantic and phonological networks connectivity during rest. Higher maternal depression at 4 years moderated the relationship between early depression scores and functional connectivity within the phonological network. CONCLUSIONS: Maternal depression in the first year of life is related to functional connections of phonological processing and enhanced by current maternal depression levels. We conclude that after a mother gives birth, resources should be provided to minimize depressive symptoms and interventions should be applied to support their child's language development for future reading acquisition.

Clinical, cortical thickness and neural activity predictors of future affective lability in youth at risk for bipolar disorder: initial discovery and independent sample replication.

We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n = 41, age = 14, SD = 2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n = 55, age = 13.7, SD = 1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of major depressive disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future-specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.

Maternal depression is associated with altered functional connectivity between neural circuits related to visual, auditory, and cognitive processing during stories listening in preschoolers.

BACKGROUND: Maternal depression can influence the early activity of a mother reading stories to a young child, as depressed mothers are less likely to read to their children. Here, maternal depression association to neurobiological circuitry of narrative comprehension, visualization, and executive functions during stories listening was examined in 21 4-year-old girls and their mothers. Maternal depression scores were collected from the mothers, and functional MRI during stories listening was collected from the children. RESULTS: Increased maternal depression was related to decreased functional connectivity between visualization and auditory regions and increased connectivity between the right visual cortex and dorsolateral prefrontal cortex in the children. CONCLUSIONS: This study highlights the need to monitor maternal depression and provide interventions to ensure positive linguistic outcomes in children.

Associations between home literacy environment, brain white matter integrity and cognitive abilities in preschool-age children.

AIM: Caregiver-child reading is advocated by health organisations, citing cognitive and neurobiological benefits. The influence of home literacy environment (HLE) on brain structure prior to kindergarten has not previously been studied. METHODS: Preschool-age children completed assessments of language (EVT-2, CTOPP-2 Rapid Object Naming) and emergent literacy skills (Get Ready to Read!, The Reading House) followed by diffusion tensor imaging (DTI). Parents completed a survey of HLE (StimQ-P2 READ), which has four subscales. DTI measures included axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA). RESULTS: Forty-seven children completed DTI (54 ± 7 months, range 36-63; 27 girls). StimQ-P2 READ scores correlated with higher EVT-2, GRTR and TRH scores, controlling for age and gender (P < .01), and also with lower AD, RD and MD in tracts supporting language and literacy skills, controlling for age, gender and income (P < .05, family-wise error corrected). Correlations were strongest for the Bookreading Quantity subscale, including with higher scores on all cognitive measures including CTOPP-2, and also with higher FA in left-lateralised literacy-supporting tracts, controlling for age, gender and income. CONCLUSION: More nurturing home reading environment prior to kindergarten may stimulate brain development supporting language and literacy skills, reinforcing the need for further study.

Neonatal Functional and Structural Connectivity Are Associated with Cerebral Palsy at Two Years of Age.

OBJECTIVE: The accuracy of structural magnetic resonance imaging (MRI) to predict later cerebral palsy (CP) in newborns with perinatal brain injury is variable. Diffusion tensor imaging (DTI) and task-based functional MRI (fMRI) show promise as predictive tools. We hypothesized that infants who later developed CP would have reduced structural and functional connectivity as compared with those without CP. STUDY DESIGN: We performed DTI and fMRI using a passive motor task at 40 to 48 weeks' postmenstrual age in 12 infants with perinatal brain injury. CP was diagnosed at age 2 using a standardized examination. RESULTS: Five infants had CP at 2 years of age, and seven did not have CP. Tract-based spatial statistics showed a widespread reduction of fractional anisotropy (FA) in almost all white matter tracts in the CP group. Using the median FA value in the corticospinal tracts as a cutoff, FA was 100% sensitive and 86% specific to predict CP compared with a sensitivity of 60 to 80% and a specificity of 71% for structural MRI. During fMRI, the CP group had reduced functional connectivity from the right supplemental motor area as compared with the non-CP group. CONCLUSION: DTI and fMRI obtained soon after birth are potential biomarkers to predict CP in newborns with perinatal brain injury.

Developmental changes in functional brain networks from birth through adolescence.

Investigation of the brain connectome using functional magnetic resonance imaging (fMRI) and measures derived from graph theory analysis has emerged as a new approach to study brain development, cognitive function, and neurophysiological disorders. Here we use graph theory analysis to examine the influence of age, sex, and neurocognitive measures on developmental changes to the global and regional topology of functional brain networks derived from fMRI data recorded in 189 healthy subjects from the age of 0-18 years during rest. We observed that Global Efficiency and Rich-Club coefficient increased with age and Local Efficiency and Small-Worldness decreased with age, while Modularity at the global level showed an inverted U-shaped trajectory during development. Marginally significant differences were observed in Local Efficiency, Small-Worldness, and Modularity at a global level between boys and girls throughout development. We also examine the effects of neurocognitive measures in boys and girls globally and locally. Our results provide new insight to understand brain maturation of functional brain connectome and its relation to cognitive development from birth through adolescence.

Extremely preterm children exhibit increased interhemispheric connectivity for language: findings from fMRI-constrained MEG analysis.

Children born extremely preterm are at significant risk for cognitive impairment, including language deficits. The relationship between preterm birth and neurological changes that underlie cognitive deficits is poorly understood. We use a stories-listening task in fMRI and MEG to characterize language network representation and connectivity in children born extremely preterm (n = 15, <28 weeks gestation, ages 4-6 years), and in a group of typically developing control participants (n = 15, term birth, 4-6 years). Participants completed a brief neuropsychological assessment. Conventional fMRI analyses revealed no significant differences in language network representation across groups (p > .05, corrected). The whole-group fMRI activation map was parcellated to define the language network as a set of discrete nodes, and the timecourse of neuronal activity at each position was estimated using linearly constrained minimum variance beamformer in MEG. Virtual timecourses were subjected to connectivity and network-based analyses. We observed significantly increased beta-band functional connectivity in extremely preterm compared to controls (p < .05). Specifically, we observed an increase in connectivity between left and right perisylvian cortex. Subsequent effective connectivity analyses revealed that hyperconnectivity in preterms was due to significantly increased information flux originating from the right hemisphere (p < 0.05). The total strength and density of the language network were not related to language or nonverbal performance, suggesting that the observed hyperconnectivity is a "pure" effect of prematurity. Although our extremely preterm children exhibited typical language network architecture, we observed significantly altered network dynamics, indicating reliance on an alternative neural strategy for the language task.

Maternal reading fluency is positively associated with greater functional connectivity between the child's future reading network and regions related to executive functions and language processing in preschool-age children.

The role of the parent or educator in a child's learning is a key feature in child development. Evidence supports the impact of early language exposure for future language and cognitive abilities and of home reading environment on neural circuits supporting language and reading. As shared parent-child reading is largely contingent on the reading ability of the parent, the aim of the current study was to explore association of parental reading ability on functional connectivity of brain networks involved with reading acquisition in their children. Twenty-two 4-year-old girls and their mothers participated in the current study. Maternal reading fluency was applied as predictors of functional connectivity analyses of a stories-listening functional MRI task. Results indicate a positive association between maternal fluency scores and greater functional connectivity between regions in the future reading network and brain regions supporting language and cognitive control in the children. Maternal reading fluency is important in facilitating development of a child's reading network. Implications regarding shared reading are discussed, and an extended ecological model for child language and literacy development is proposed.

Neurite density index is sensitive to age related differences in the developing brain.

PURPOSE: White matter development during childhood and adolescence is characterised by increasing white matter coherence and organisation. Commonly used scalar metrics, such as fractional anisotropy (FA), are sensitive to multiple mechanisms of white matter change and therefore unable to distinguish between mechanisms that change during development. We investigate the relationship between age and neurite density index (NDI) from neurite orientation dispersion and density imaging (NODDI), and the age-classification accuracy of NDI compared with FA, in a developmental cohort. METHOD: Diffusion-weighted imaging data from 72 children and adolescents between the ages of 4-19 was collected (M=10.42, SD=3.99, 36 male). We compared NODDI metrics against conventional DTI metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD] and radial diffusivity [RD]) in terms of their relationship to age. An ROC analysis was also performed to assess the ability of each metric to classify older and younger participants. RESULTS: NDI exhibited a stronger relationship with age (median R2=.60) compared with MD (median R2=.39), FA (median R2=.27), AD (median R2=.14), and RD (median R2=.35) in a high proportion of white matter tracts. When participants were divided into an older and younger group, NDI achieved the best classification (median area under the curve [AUC]=.89), followed by MD (median AUC=.81), FA (median AUC=.80), RD (median AUC=.81), and AD (median AUC=.64). CONCLUSION: Our results demonstrate the sensitivity of NDI to age-related differences in white matter microstructural organisation over development. Importantly, NDI is more sensitive to such developmental changes compared to commonly used DTI metrics. This knowledge provides justification for implementing NODDI metrics in developmental studies.

The canonical semantic network supports residual language function in chronic post-stroke aphasia.

Current theories of language recovery after stroke are limited by a reliance on small studies. Here, we aimed to test predictions of current theory and resolve inconsistencies regarding right hemispheric contributions to long-term recovery. We first defined the canonical semantic network in 43 healthy controls. Then, in a group of 43 patients with chronic post-stroke aphasia, we tested whether activity in this network predicted performance on measures of semantic comprehension, naming, and fluency while controlling for lesion volume effects. Canonical network activation accounted for 22%-33% of the variance in language test scores. Whole-brain analyses corroborated these findings, and revealed a core set of regions showing positive relationships to all language measures. We next evaluated the relationship between activation magnitudes in left and right hemispheric portions of the network, and characterized how right hemispheric activation related to the extent of left hemispheric damage. Activation magnitudes in each hemispheric network were strongly correlated, but four right frontal regions showed heightened activity in patients with large lesions. Activity in two of these regions (inferior frontal gyrus pars opercularis and supplementary motor area) was associated with better language abilities in patients with larger lesions, but poorer language abilities in patients with smaller lesions. Our results indicate that bilateral language networks support language processing after stroke, and that right hemispheric activations related to extensive left hemispheric damage occur outside of the canonical semantic network and differentially relate to behavior depending on the extent of left hemispheric damage. Hum Brain Mapp 38:1636-1658, 2017. © 2016 Wiley Periodicals, Inc.

Shared Reading Quality and Brain Activation during Story Listening in Preschool-Age Children.

OBJECTIVE: To explore the relationship between maternal shared reading quality (verbal interactivity and engagement) and brain function during story listening in at-risk, preschool-age children, in the context of behavioral evidence and American Academy of Pediatrics, recommendations. STUDY DESIGN: In this cross-sectional study, 22 healthy, 4-year-old girls from low socioeconomic status households completed functional magnetic resonance imaging using an established story listening task, followed by videotaped observation of uncoached mother-daughter reading of the same, age-appropriate picture book. Shared reading quality was independently scored applying dialogic reading and other evidence-based criteria reflecting interactivity and engagement, and applied as a predictor of neural activation during the functional magnetic resonance imaging task, controlling for income and maternal education. RESULTS: Shared reading quality scores were generally low and negatively correlated with maternal distraction by smartphones (P < .05). Scores were positively correlated with activation in left-sided brain areas supporting expressive and complex language, social-emotional integration, and working memory (P <.05, false discovery rate corrected). CONCLUSIONS: Maternal shared reading quality is positively correlated with brain activation supporting complex language, executive function, and social-emotional processing in at-risk, preschool-age children. These findings represent novel neural biomarkers of how this modifiable aspect of home reading environment may influence foundational emergent literacy skills, reinforce behavioral evidence and American Academy of Pediatrics, recommendations, and underscore the potential of dialogic reading interventions to promote healthy brain development, especially in at-risk households.

Obese adolescents with type 2 diabetes perform worse than controls on cognitive and behavioral assessments.

BACKGROUND: Children with type 1 diabetes demonstrate worse cognitive performance compared with their peers. Little is known regarding the cognitive and behavioral performance in obese adolescents with type 2 diabetes. METHODS: Cross sectional evaluation of 20 obese adolescents with type 2 diabetes and 20 healthy adolescents was performed in Cincinnati, Ohio. Cognitive tests that included measures of processing speed, working memory, verbal and semantic fluency and parent reports of executive function and problem behavior were compared. Academic achievement and the relationship between cognitive/behavioral scores and diabetes duration and diabetes control (hemoglobin A1c) were assessed in the type 2 diabetes group only. RESULTS: The type 2 diabetes group had mean duration of diabetes of 2.8 ± 2.2 yr and hemoglobin A1c of 7.9 ± 2.2%. Adolescents with type 2 diabetes scored lower than controls on tests of working and verbal memory and processing speed (all p < 0.05) and worse for Internalizing, Externalizing, and Total Problems behaviors on the Child Behavior Checklist (all p < 0.05). Adolescents with type 2 diabetes scored below the population mean in academic achievement, most notably calculation. Working memory and processing speed were negatively correlated with duration of diabetes (r = -0.50 and -0.47, respectively, p < 0.05). CONCLUSIONS: Obese youth with type 2 diabetes score poorly compared with controls on multiple assessments of cognitive function and adaptive behavior. Further work is needed to determine if these effects are driven by obesity, diabetes or other demographic and socioeconomic risk factors.

Arcuate fasciculus asymmetry has a hand in language function but not handedness.

The importance of relationships between handedness, language lateralization and localization, and white matter tracts for language performance is unclear. The goal of the study was to investigate these relationships by examining arcuate fasciculus (AF) structural asymmetry (DTI) and functional asymmetry (fMRI) in language circuits, handedness, and linguistic performance. A large sample of right-handed (n = 158) and atypical-handed (n = 82) healthy adults underwent DTI at 3 T to assess number of streamlines and fractional anisotropy (FA) of the AF, and language fMRI. Language functions were assessed using standard tests of vocabulary, naming, verbal fluency, and complex ideation. Laterality indices (LIs) illustrated degree of asymmetry and lateralization patterns for the AF (streamlines and FA) and verb generation fMRI. Both handedness groups showed leftward lateralization bias for streamline and fMRI LIs and symmetry for FA LI. The proportion of subjects with left, right, or symmetric lateralization were similar between groups if based on AF LIs, but differed if based on fMRI LIs (p = 0.0016). Degree of right-handedness was not associated with AF lateralization, but was associated with fMRI language lateralization (p = 0.0014). FA LI was not associated with performance on language assessments, but streamline LI was associated with better vocabulary and complex ideation performance in atypical-handed subjects (p = 0.022 and p = 0.0098, respectively), and better semantic fluency in right-handed subjects (p = 0.047); however, these did not survive multiple comparisons correction. We provide evidence that AF asymmetry is independent of hand preference, and while degree of right-handedness is associated with hemispheric language lateralization, the majority of atypical-handed individuals are left-lateralized for language. Hum Brain Mapp 37:3297-3309, 2016. © 2016 Wiley Periodicals, Inc.

Functional and structural connectivity of the visual system in infants with perinatal brain injury.

BACKGROUND: Infants with perinatal brain injury are at risk of later visual problems. Advanced neuroimaging techniques show promise to detect functional and structural alterations of the visual system. We hypothesized that infants with perinatal brain injury would have less brain activation during a visual functional magnetic resonance imaging (fMRI) task and reduced task-based functional connectivity and structural connectivity as compared with healthy controls. METHODS: Ten infants with perinatal brain injury and 20 control infants underwent visual fMRI and diffusion tensor imaging (DTI) during natural sleep with no sedation. Activation maps, functional connectivity maps, and structural connectivity were analyzed and compared between the two groups. RESULTS: Most infants in both groups had negative activation in the visual cortex during the fMRI task. Infants with brain injury showed reduced activation in the occipital cortex, weaker connectivity between visual areas and other areas of the brain during the visual task, and reduced fractional anisotropy in white matter tracts projecting to visual regions, as compared with control infants. CONCLUSION: Infants with brain injury sustained in the perinatal period showed evidence of decreased brain activity and functional connectivity during a visual task and altered structural connectivity as compared with healthy term neonates.

Changes of White Matter Diffusion Anisotropy in Response to a 6-Week iPad Application-Based Occupational Therapy Intervention in Children with Surgically Treated Hydrocephalus: A Pilot Study.

Objective Our aims were (1) to test whether diffusion tensor imaging (DTI) could detect underlying white matter (WM) changes after a 6-week iPad application-based occupational therapy (OT) intervention in children with surgically treated hydrocephalus (HCP); and (2) to explore the association between WM changes and performance outcomes. Methods Five children (age range: 6.05-9.10 years) with surgically treated HCP completed an intensive iPad-based OT intervention targeting common domains of long-term deficits in children with HCP. The intervention included 6 weekly sessions in an OT clinic supplementing home-based program (1 hour/day, 4 days/week). DTI and neuropsychological assessments were performed before and after the intervention. Observation After the therapy, significant increases in fractional anisotropy (FA) and/or decreases in radial diffusivity were found in extensive WM areas. All participants demonstrated an increased perceptual reasoning index (PRI, Wechsler Abbreviated Scale of Intelligence: 2nd edition, PRI gains = 14.20 ± 7.56, p = 0.014). A significant positive correlation was found between PRI increase and the increase of FA in the right posterior limb of the internal capsule and the right external capsule (both p < 0.05). Conclusion This study provides initial evidence of DTI's sensitivity to detect subtle WM changes associated with performance improvements in response to a 6-week OT intervention in children with HCP.

fMRI as a Preimplant Objective Tool to Predict Postimplant Oral Language Outcomes in Children with Cochlear Implants.

OBJECTIVES: Despite the positive effects of cochlear implantation, postimplant variability in speech perception and oral language outcomes is still difficult to predict. The aim of this study was to identify neuroimaging biomarkers of postimplant speech perception and oral language performance in children with hearing loss who receive a cochlear implant. The authors hypothesized positive correlations between blood oxygen level-dependent functional magnetic resonance imaging (fMRI) activation in brain regions related to auditory language processing and attention and scores on the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition (CELF-P2) and the Early Speech Perception Test for Profoundly Hearing-Impaired Children (ESP), in children with congenital hearing loss. DESIGN: Eleven children with congenital hearing loss were recruited for the present study based on referral for clinical MRI and other inclusion criteria. All participants were <24 months at fMRI scanning and <36 months at first implantation. A silent background fMRI acquisition method was performed to acquire fMRI during auditory stimulation. A voxel-based analysis technique was utilized to generate z maps showing significant contrast in brain activation between auditory stimulation conditions (spoken narratives and narrow band noise). CELF-P2 and ESP were administered 2 years after implantation. Because most participants reached a ceiling on ESP, a voxel-wise regression analysis was performed between preimplant fMRI activation and postimplant CELF-P2 scores alone. Age at implantation and preimplant hearing thresholds were controlled in this regression analysis. RESULTS: Four brain regions were found to be significantly correlated with CELF-P2 scores. These clusters of positive correlation encompassed the temporo-parieto-occipital junction, areas in the prefrontal cortex and the cingulate gyrus. For the story versus silence contrast, CELF-P2 core language score demonstrated significant positive correlation with activation in the right angular gyrus (r = 0.95), left medial frontal gyrus (r = 0.94), and left cingulate gyrus (r = 0.96). For the narrow band noise versus silence contrast, the CELF-P2 core language score exhibited significant positive correlation with activation in the left angular gyrus (r = 0.89; for all clusters, corrected p < 0.05). CONCLUSIONS: Four brain regions related to language function and attention were identified that correlated with CELF-P2. Children with better oral language performance postimplant displayed greater activation in these regions preimplant. The results suggest that despite auditory deprivation, these regions are more receptive to gains in oral language development performance of children with hearing loss who receive early intervention via cochlear implantation. The present study suggests that oral language outcome following cochlear implant may be predicted by preimplant fMRI with auditory stimulation using natural speech.

Evidence that neurovascular coupling underlying the BOLD effect increases with age during childhood.

Functional MRI using blood-oxygen-level-dependent (BOLD) imaging has provided unprecedented insights into the maturation of the human brain. Task-based fMRI studies have shown BOLD signal increases with age during development (ages 5-18) for many cognitive domains such as language and executive function, while functional connectivity (resting-state) fMRI studies investigating regionally synchronous BOLD fluctuations have revealed a developing functional organization of the brain from a local into a more distributed architecture. However, interpretation of these results is confounded by the fact that the BOLD signal is directly related to blood oxygenation driven by changes in blood flow and only indirectly related to neuronal activity, and may thus be affected by changing neuronal-vascular coupling. BOLD signal and cerebral blood flow (CBF) were measured simultaneously in a cohort of 113 typically developing awake participants ages 3-18 performing a narrative comprehension task. Using a novel voxelwise wild bootstrap analysis technique, an increased ratio of BOLD signal to relative CBF signal change with age (indicative of increased neuronal-vascular coupling) was seen in the middle temporal gyri and the left inferior frontal gyrus. Additionally, evidence of decreased relative oxygen metabolism (indicative of decreased neuronal activity) with age was found in the same regions. These findings raise concern that results of developmental BOLD studies cannot be unambiguously attributed to neuronal activity. Astrocytes and astrocytic processes may significantly affect the maturing functional architecture of the brain, consistent with recent research demonstrating a key role for astrocytes in mediating increased CBF following neuronal activity and for astrocyte processes in modulating synaptic connectivity.