Comparison of cerebral safety after atrial fibrillation using pulsed field and thermal ablation: Results of the neurological assessment subgroup in the ADVENT trial.

BACKGROUND: Atrial fibrillation (AF) ablation carries the risk of silent cerebral event (SCE) and silent cerebral lesion (SCL). Although "silent," these may have long-term clinical implications and are challenging to study as postprocedural magnetic resonance imaging (MRI) is not standard of care. OBJECTIVE: The neurological assessment subgroup (NAS) of ADVENT compared cerebral effects of pulsed field ablation (PFA) with standard-of-care thermal ablation. METHODS: The NAS included consecutive randomized PFA and thermal ablation patients who received postprocedural brain MRI 12-48 hours after ablation. Patients with apparent SCE or SCL findings underwent a modified Rankin scale assessment. MRI images were subsequently reviewed by a blinded brain imaging core laboratory. RESULTS: In total, 77 patients with paroxysmal AF were enrolled at 6 centers; 71 had analyzable scans (34 PFA; 37 thermal ablation). Through individual center review, 6 PFA and 4 thermal scans were identified as SCE/SCL positive, of which 3 PFA and 0 thermal SCE/SCL findings were confirmed by a blinded core laboratory. MRI findings revealed 1 patient with 2- to 4-mm SCEs, 1 patient with a 3-mm SCE, and 1 patient with 2 SCLs (5.5 mm and 11 mm). All modified Rankin scale and National Institutes of Health Stroke Scale scores were 0 before discharge and at 90-day follow-up. There were only 2 neurological safety events (1 transient ischemic attack [PFA] and 1 stroke [thermal ablation]) in the ADVENT study, neither of which was part of the NAS. CONCLUSION: The ADVENT trial provides the first prospective, randomized data on the cerebral impact of PFA and thermal ablation of AF. Incidence of SCE/SCL after ablation in the NAS was low.

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.

Language First, Cognition Later: Different Trajectories of Subcomponents of the Future-Reading Network in Processing Narratives from Kindergarten to Adolescence.

Narrative comprehension is a linguistic ability that emerges early in life and has a critical role in language development, reading acquisition, and comprehension. According to the Simple View of Reading model, reading is acquired through word decoding and linguistic comprehension. Here, within and between networks, functional connectivity in several brain networks supporting both language and reading abilities was examined from prereading to proficient reading age in 32 healthy children, ages 5-18 years, scanned annually while listening to stories over 12 years. Functional connectivity changes within and between the networks were assessed and compared between the years using hierarchical linear regression and were related to reading abilities. At prereading age, the networks related to basic language processing accounted for 32.5% of the variation of reading ability at reading age (at 12-14 years) (R2 = 0.325, p = 0.05). At age 17, more complex cognitive networks were involved and accounted for 97.4% of the variation in reading ability (R2 = 0.974, p = 0.022). Overall, networks composing the future-reading network are highly involved in processing narratives along development; however, networks related to semantic, phonological, and syntactic processing predict reading ability earlier in life, and more complex networks predict reading proficiency later in life.

Bayesian MEG time courses with fMRI priors.

Magnetoencephalography (MEG) records brain activity with excellent temporal and good spatial resolution, while functional magnetic resonance imaging (fMRI) offers good temporal and excellent spatial resolution. The aim of this study is to implement a Bayesian framework to use fMRI data as spatial priors for MEG inverse solutions. We used simulated MEG data with both evoked and induced activity and experimental MEG data from sixteen participants to examine the effectiveness of using fMRI spatial priors in MEG source reconstruction. For simulated MEG data, incorporating the prior information from fMRI increased the spatial resolution of MEG source reconstruction by 3 mm on average. For experimental MEG data, fMRI spatial information reduced the spurious clusters for evoked activity and showed more left-lateralized activation pattern for induced activity. The use of fMRI spatial priors greatly reduced location error for induced source in MEG data. Our results provide empirical evidence that the use of fMRI spatial priors improves the accuracy of MEG source reconstruction. The combined MEG and fMRI approach can provide neuroimaging data with better spatial and temporal resolutions to add another perspective to our understanding of the neurobiology of language. The potential clinical applications include pre-surgical evaluation of language function for epilepsy patients and evaluation of language network for children with language disorders.

Validation of The Reading House and Association With Cortical Thickness.

BACKGROUND AND OBJECTIVES: The American Academy of Pediatrics recommends literacy and school readiness promotion during well visits. The Reading House (TRH) is a children's book-based screener of emergent literacy skills in preschool-aged children. Vocabulary, rhyming, and rapid naming are core emergent skills, and reading abilities are associated with thicker cortex in the left hemisphere. Our objective was to expand validity of TRH relative to these skills and explore association with cortical thickness. METHODS: Healthy preschool-aged children completed MRI including a T1-weighted anatomic scan. Before MRI, TRH and assessments of rapid naming (Comprehensive Test of Phonological Processing, Second Edition), rhyming (Pre-Reading Inventory of Phonological Awareness), vocabulary (Expressive Vocabulary Test, Second Edition), and emergent literacy (Get Ready to Read!) were administered. Analyses included Spearman-ρ correlations (r ρ) accounting for age, sex, and socioeconomic status (SES). MRI analyses involved whole-brain measures of cortical thickness relative to TRH scores, accounting for covariates. RESULTS: Seventy children completed assessments (36-63 months old; 36 female) and 52 completed MRI (37-63 months; 29 female). TRH scores were positively correlated with Comprehensive Test of Phonological Processing, Second Edition (r ρ = 0.61), Expressive Vocabulary Test, Second Edition (r ρ = 0.54), Get Ready to Read! (r ρ = 0.87), and Pre-Reading Inventory of Phonological Awareness scores (r ρ = 0.64; all P < .001). These correlations remained statistically significant across age, sex, and SES groups. TRH scores were correlated with greater thickness in left-sided language and visual cortex (P-family-wise error <.05), which were similar for higher SES yet more bilateral and frontal for low SES, reflecting a less mature pattern (P-family-wise error <.10). CONCLUSIONS: These findings expand validation evidence for TRH as a screening tool for preschool-aged children, including associations with emergent skills and cortical thickness, and suggest important differences related to SES.

Extremely preterm children demonstrate hyperconnectivity during verb generation: A multimodal approach.

Children born extremely preterm (EPT, <28 weeks gestation) are at risk for delays in development, including language. We use fMRI-constrained magnetoencephalography (MEG) during a verb generation task to assess the extent and functional connectivity (phase locking value, or PLV) of language networks in a large cohort of EPT children and their term comparisons (TC). 73 participants, aged 4 to 6 years, were enrolled (42 TC, 31 EPT). There were no significant group differences in age, sex, race, ethnicity, parental education, or family income. There were significant group differences in expressive language scores (p < 0.05). Language representation was not significantly different between groups on fMRI, with task-specific activation involving bilateral temporal and left inferior frontal cortex. There were group differences in functional connectivity seen in MEG. To identify a possible subnetwork contributing to focal spectral differences in connectivity, we ran Network Based Statistics analyses. For both beta (20-25 Hz) and gamma (61-70 Hz) bands, we observed a subnetwork showing hyperconnectivity in the EPT group (p < 0.05). Network strength was computed for the beta and gamma subnetworks and assessed for correlation with language performance. For the EPT group exclusively, strength of the subnetwork identified in the gamma frequency band was positively correlated with expressive language scores (r = 0.318, p < 0.05). Thus, hyperconnectivity is positively related to language for EPT children and might represent a marker for resiliency in this population.

Extremely Preterm Children Demonstrate Interhemispheric Hyperconnectivity During Verb Generation: a Multimodal Approach.

Children born extremely preterm (EPT, <28 weeks gestation) are at risk for delays in development, including language. We use fMRI-constrained magnetoencephalography (MEG) during a verb generation task to assess the extent and functional connectivity (phase locking value, or PLV) of language networks in a large cohort of EPT children and their term comparisons (TC). 73 participants, aged 4 to 6 years, were enrolled (42 TC, 31 EPT). There were no significant group differences in age, sex, race, ethnicity, parental education, or family income. There were significant group differences in expressive language scores (p<0.05). Language representation was not significantly different between groups on fMRI, with task-specific activation involving bilateral temporal and left inferior frontal cortex. There were group differences in functional connectivity seen in MEG. To identify a possible subnetwork contributing to focal spectral differences in connectivity, we ran Network Based Statistics analyses. For both beta (20-25 Hz) and gamma (61-70 Hz) bands, we observed a subnetwork showing hyperconnectivity in the EPT group (p<0.05). Network strength was computed for the beta and gamma subnetworks and assessed for correlation with language performance. For the EPT group, exclusively, strength of the subnetwork identified in the gamma frequency band was positively correlated with expressive language scores (r=0.318, p<0.05). Thus, interhemispheric hyperconnectivity is positively related to language for EPT children and might represent a marker for resiliency in this population.

Extremely preterm children exhibit altered cortical thickness in language areas.

Children born extremely preterm (< 28 weeks gestation, EPT) are at increased risk for language and other neurocognitive deficits compared to term controls (TC). Prior studies have reported both increases and decreases in cortical thickness in EPT across the cerebrum. These studies have not formally normalized for intracranial volume (ICV), which is especially important as EPT children often have smaller stature, head size, and ICV. We previously reported increased interhemispheric functional and structural connectivity in a well-controlled group of school-aged EPT children with no known brain injury or neurological deficits. Functional and structural hyperconnectivity between left and right temporoparietal regions was positively related with language scores in EPT, which may be reflected in measures of cortical thickness. To characterize possible language network cortical thickness effects, 15 EPT children and 15 TC underwent standardized assessments of language and structural magnetic resonance imaging at 4 to 6 years of age. Images were subjected to volumetric and cortical thickness analyses using FreeSurfer. Whole-brain analyses of cortical thickness were conducted both with and without normalization by ICV. Non-normalized results showed thinner temporal cortex for EPT, while ICV-normalized results showed thicker cortical regions in the right temporal lobe (FDRq = 0.05). Only ICV-normalized results were significantly related to language scores, with right temporal cortical thickness being positively correlated with performance.

Rewiring the extremely preterm brain: Altered structural connectivity relates to language function.

Children born preterm are at increased risk for cognitive impairment, with higher-order functions such as language being especially vulnerable. Previously, we and others have reported increased interhemispheric functional connectivity in children born extremely preterm; the finding appears at odds with literature showing decreased integrity of the corpus callosum, the primary commissural bundle, in preterm children. We address the apparent discrepancy by obtaining advanced measures of structural connectivity in twelve school-aged children born extremely preterm (<28 weeks) and ten term controls. We hypothesize increased extracallosal structural connectivity might support the functional hyperconnectivity we had previously observed. Participants were aged four to six years at time of study and groups did not differ in age, sex, race, ethnicity, or socioeconomic status. Whole-brain and language-network-specific (functionally-constrained) connectometry analyses were performed. At the whole-brain level, preterm children had decreased connectivity in the corpus callosum and increased connectivity in the cerebellum versus controls. Functionally-constrained analyses revealed significantly increased extracallosal connectivity between bilateral temporal regions in preterm children (FDRq <0.05). Connectivity within these extracallosal pathways was positively correlated with performance on standardized language assessments in children born preterm (FDRq <0.001), but unrelated to performance in controls. This is the first study to identify anatomical substrates for increased interhemispheric functional connectivity in children born preterm; increased reliance on an extracallosal pathway may represent a biomarker for resiliency following extremely preterm birth.

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.

Associations Between Screen-Based Media Use and Brain White Matter Integrity in Preschool-Aged Children.

Importance: The American Academy of Pediatrics (AAP) recommends limits on screen-based media use, citing its cognitive-behavioral risks. Screen use by young children is prevalent and increasing, although its implications for brain development are unknown. Objective: To explore the associations between screen-based media use and integrity of brain white matter tracts supporting language and literacy skills in preschool-aged children. Design, Setting, and Participants: This cross-sectional study of healthy children aged 3 to 5 years (n = 47) was conducted from August 2017 to November 2018. Participants were recruited at a US children's hospital and community primary care clinics. Exposures: Children completed cognitive testing followed by diffusion tensor imaging (DTI), and their parent completed a ScreenQ survey. Main Outcomes and Measures: ScreenQ is a 15-item measure of screen-based media use reflecting the domains in the AAP recommendations: access to screens, frequency of use, content viewed, and coviewing. Higher scores reflect greater use. ScreenQ scores were applied as the independent variable in 3 multiple linear regression models, with scores in 3 standardized assessments as the dependent variable, controlling for child age and household income: Comprehensive Test of Phonological Processing, Second Edition (CTOPP-2; Rapid Object Naming subtest); Expressive Vocabulary Test, Second Edition (EVT-2; expressive language); and Get Ready to Read! (GRTR; emergent literacy skills). The DTI measures included fractional anisotropy (FA) and radial diffusivity (RD), which estimated microstructural organization and myelination of white matter tracts. ScreenQ was applied as a factor associated with FA and RD in whole-brain regression analyses, which were then narrowed to 3 left-sided tracts supporting language and emergent literacy abilities. Results: Of the 69 children recruited, 47 (among whom 27 [57%] were girls, and the mean [SD] age was 54.3 [7.5] months) completed DTI. Mean (SD; range) ScreenQ score was 8.6 (4.8; 1-19) points. Mean (SD; range) CTOPP-2 score was 9.4 (3.3; 2-15) points, EVT-2 score was 113.1 (16.6; 88-144) points, and GRTR score was 19.0 (5.9; 5-25) points. ScreenQ scores were negatively correlated with EVT-2 (F2,43 = 5.14; R2 = 0.19; P < .01), CTOPP-2 (F2,35 = 6.64; R2 = 0.28; P < .01), and GRTR (F2,44 = 17.08; R2 = 0.44; P < .01) scores, controlling for child age. Higher ScreenQ scores were correlated with lower FA and higher RD in tracts involved with language, executive function, and emergent literacy abilities (P < .05, familywise error-corrected), controlling for child age and household income. Conclusions and Relevance: This study found an association between increased screen-based media use, compared with the AAP guidelines, and lower microstructural integrity of brain white matter tracts supporting language and emergent literacy skills in prekindergarten children. The findings suggest further study is needed, particularly during the rapid early stages of brain development.

Differences in functional brain network connectivity during stories presented in audio, illustrated, and animated format in preschool-age children.

The American Academy of Pediatrics (AAP) recommends that parents begin reading to their children soon after birth, and limits on screen-based media. Benefits of traditional book-sharing are well documented in children, while cited deleterious effects of animated content on narrative processing are controversial. The influence of story format on underlying functional brain networks has not previously been studied. Thirty-three healthy children were recruited for this study via advertisement at an academic medical center, which involved functional magnetic resonance imaging (fMRI) at a single visit. Twenty-seven of them completed fMRI (82%; 15 boys, 12 girls; mean 58 ± 8 months old). The fMRI protocol involved the presentation of 3 similar, unrhymed stories by the same author lasting 5 min each in audio, illustrated, and animated format during separate runs, followed by a test of factual recall. Within- and between-network functional connectivity (FC) was compared across formats involving five functional networks, which were defined via literature review and refined via a data-driven parcellation method: visual perception, visual imagery, language, Default Mode (DMN), and cerebellar association. For illustration relative to audio, FC was decreased within the language network and increased between visual, DMN, and cerebellar networks, suggesting decreased strain on the language network afforded by pictures and visual imagery. Between-network connectivity was decreased for all networks for animation relative to the other formats, particularly illustration, suggesting a bias towards visual perception at the expense of network integration. These findings suggest substantial differences in functional brain network connectivity for animated and more traditional story formats in preschool-age children, reinforcing the appeal of illustrated storybooks at this age to provide efficient scaffolding for language, and suggesting novel neurobiological correlates of how functional networks may contribute to this process.

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.

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.

Functional Connectivity of Attention, Visual, and Language Networks During Audio, Illustrated, and Animated Stories in Preschool-Age Children.

The American Academy of Pediatrics recommends that parents read with their children early and often and limits on screen-based media. While book sharing may benefit attention in children, effects of animated content are controversial, and the influence of either on attention networks has not previously been studied. This study involved functional magnetic resonance imaging (fMRI) of three separate active-task scans composed of similar 5-min stories presented in the same order for each child (audio → illustrated → animated), followed by assessment of comprehension. Five functional brain networks were defined a priori through literature review: dorsal attention network (DAN), ventral attention network (VAN), language (L), visual imagery (VI), and visual perception (VP). Analyses involved comparison of functional connectivity (FC) within- and between networks across formats, applying false discovery rate correction. Twenty-seven of 33 children completed fMRI (82%; 15 boys, 12 girls; mean 58 ± 8 months old). Comprehension of audio and illustrated stories was equivalent and lower for animation (p < 0.05). For illustration relative to audio, FC within DAN and VAN and between each of these and all other networks was similar, lower within-L, and higher between VI-VP, suggesting reduced strain on the language network using illustrations and imagery. For animation relative to illustration, FC was lower between DAN-L, VAN-VP, VAN-VI, L-VI, and L-VP, suggesting less focus on narrative, reorienting to imagery, and visual-language integration. These findings suggest that illustrated storybooks may be optimal at this age to encourage integration of attention, visual, and language networks, while animation may bias attention toward VP.

Changes in functional organization and functional connectivity during story listening in children with benign childhood epilepsy with centro-temporal spikes.

Children with Benign Epilepsy with Centrotemporal Spikes (BECTS), despite high likelihood for seizure remission, are reported to have subtle difficulties in language and other cognitive skills. We used functional MRI and a story listening task to examine the effect of BECTS on patterns of activation and connectivity. Language and cognitive skills were assessed using standardized measures. Twenty-four children with recently diagnosed BECTS and 40 typically-developing children participated. In a functionally-defined region of interest in right inferior frontal gyrus, BECTS patients showed a lower level of activation. Across both groups combined, increased activation in superior/middle temporal regions of interest was associated with better language scores. Connectivity in the story processing network was similar between groups, but connectivity within left inferior frontal gyrus was decreased in children with BECTS. These results suggest that language networks are largely maintained in new-onset BECTS, but some subtle changes in activation and connectivity can be observed.

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.

Altered functional network connectivity in preterm infants: antecedents of cognitive and motor impairments?

Very preterm infants (≤ 31 weeks gestational age) are at high risk for brain injury and delayed development. Applying functional connectivity and graph theory methods to resting state MRI data (fcMRI), we tested the hypothesis that preterm infants would demonstrate alterations in connectivity measures both globally and in specific networks related to motor, language and cognitive function, even when there is no anatomical imaging evidence of injury. Fifty-one healthy full-term controls and 24 very preterm infants without significant neonatal brain injury, were evaluated at term-equivalent age with fcMRI. Preterm subjects showed lower functional connectivity from regions associated with motor, cognitive, language and executive function, than term controls. Examining brain networks using graph theory measures of functional connectivity, very preterm infants also exhibited lower rich-club coefficient and assortativity but higher small-worldness and no significant difference in modularity when compared to term infants. The findings provide evidence that functional connectivity exhibits deficits soon after birth in very preterm infants in key brain networks responsible for motor, language and executive functions, even in the absence of anatomical lesions. These functional network measures could serve as prognostic biomarkers for later developmental disabilities and guide decisions about early interventions.

Early prediction of cognitive deficits in very preterm infants using functional connectome data in an artificial neural network framework.

Investigation of the brain's functional connectome can improve our understanding of how an individual brain's organizational changes influence cognitive function and could result in improved individual risk stratification. Brain connectome studies in adults and older children have shown that abnormal network properties may be useful as discriminative features and have exploited machine learning models for early diagnosis in a variety of neurological conditions. However, analogous studies in neonates are rare and with limited significant findings. In this paper, we propose an artificial neural network (ANN) framework for early prediction of cognitive deficits in very preterm infants based on functional connectome data from resting state fMRI. Specifically, we conducted feature selection via stacked sparse autoencoder and outcome prediction via support vector machine (SVM). The proposed ANN model was unsupervised learned using brain connectome data from 884 subjects in autism brain imaging data exchange database and SVM was cross-validated on 28 very preterm infants (born at 23-31 weeks of gestation and without brain injury; scanned at term-equivalent postmenstrual age). Using 90 regions of interests, we found that the ANN model applied to functional connectome data from very premature infants can predict cognitive outcome at 2 years of corrected age with an accuracy of 70.6% and area under receiver operating characteristic curve of 0.76. We also noted that several frontal lobe and somatosensory regions, significantly contributed to prediction of cognitive deficits 2 years later. Our work can be considered as a proof of concept for utilizing ANN models on functional connectome data to capture the individual variability inherent in the developing brains of preterm infants. The full potential of ANN will be realized and more robust conclusions drawn when applied to much larger neuroimaging datasets, as we plan to do.

fMRI as a Preimplant Objective Tool to Predict Children's Postimplant Auditory and Language Outcomes as Measured by Parental Observations.

BACKGROUND: The trends in cochlear implantation candidacy and benefit have changed rapidly in the last two decades. It is now widely accepted that early implantation leads to better postimplant outcomes. Although some generalizations can be made about postimplant auditory and language performance, neural mechanisms need to be studied to predict individual prognosis. PURPOSE: The aim of this study was to use functional magnetic resonance imaging (fMRI) to identify preimplant neuroimaging biomarkers that predict children's postimplant auditory and language outcomes as measured by parental observation/reports. RESEARCH DESIGN: This is a pre-post correlational measures study. STUDY SAMPLE: Twelve possible cochlear implant candidates with bilateral severe to profound hearing loss were recruited via referrals for a clinical magnetic resonance imaging to ensure structural integrity of the auditory nerve for implantation. INTERVENTION: Participants underwent cochlear implantation at a mean age of 19.4 mo. All children used the advanced combination encoder strategy (ACE, Cochlear Corporation™, Nucleus® Freedom cochlear implants). Three participants received an implant in the right ear; one in the left ear whereas eight participants received bilateral implants. Participants' preimplant neuronal activation in response to two auditory stimuli was studied using an event-related fMRI method. DATA COLLECTION AND ANALYSIS: Blood oxygen level dependent contrast maps were calculated for speech and noise stimuli. The general linear model was used to create z-maps. The Auditory Skills Checklist (ASC) and the SKI-HI Language Development Scale (SKI-HI LDS) were administered to the parents 2 yr after implantation. A nonparametric correlation analysis was implemented between preimplant fMRI activation and postimplant auditory and language outcomes based on ASC and SKI-HI LDS. Statistical Parametric Mapping software was used to create regression maps between fMRI activation and scores on the aforementioned tests. Regression maps were overlaid on the Imaging Research Center infant template and visualized in MRIcro. RESULTS: Regression maps revealed two clusters of brain activation for the speech versus silence contrast and five clusters for the noise versus silence contrast that were significantly correlated with the parental reports. These clusters included auditory and extra-auditory regions such as the middle temporal gyrus, supramarginal gyrus, precuneus, cingulate gyrus, middle frontal gyrus, subgyral, and middle occipital gyrus. Both positive and negative correlations were observed. Correlation values for the different clusters ranged from -0.90 to 0.95 and were significant at a corrected p value of <0.05. Correlations suggest that postimplant performance may be predicted by activation in specific brain regions. CONCLUSIONS: The results of the present study suggest that (1) fMRI can be used to identify neuroimaging biomarkers of auditory and language performance before implantation and (2) activation in certain brain regions may be predictive of postimplant auditory and language performance as measured by parental observation/reports.