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.

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.

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.

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.

Periventricular hyperintensity in children with hydrocephalus.

BACKGROUND: Magnetic resonance images of children with hydrocephalus often include a rim of hyperintensity in the periventricular white matter (halo). OBJECTIVE: The purpose of this study was to decide between the hypothesis that the halo is caused by cerebrospinal fluid (CSF) flow during the cardiac cycle, and the alternate hypothesis that the halo is caused by anatomical changes (stretching and compression of white matter). MATERIALS AND METHODS: Participants were selected from a multicenter imaging study of pediatric hydrocephalus. We compared 19 children with hydrocephalus to a group of 52 controls. We quantified ventricle enlargement using the frontal-occipital horn ratio. We conducted qualitative and quantitative analysis of diffusion tensor imaging in the corpus callosum and posterior limb of the internal capsule. Parameters included the fractional anisotropy (FA), mean diffusivity, axial diffusivity and radial diffusivity. RESULTS: The halo was seen in 16 of the 19 children with hydrocephalus but not in the controls. The corpus callosum of the hydrocephalus group demonstrated FA values that were significantly decreased from those in the control group (P = 4 · 10(-6)), and highly significant increases were seen in the mean diffusivity and radial diffusivity in the hydrocephalus group. In the posterior limb of the internal capsule the FA values of the hydrocephalus group were higher than those for the control group (P = 0.002), and higher values in the hydrocephalus group were also noted in the axial diffusivity. We noted correlations between the diffusion parameters and the frontal-occipital horn ratio. CONCLUSION: Our results strongly support the hypothesis that the halo finding in hydrocephalus is caused by structural changes rather than pulsatile CSF flow.

Multidimensional morphometric 3D MRI analyses for detecting brain abnormalities in children: impact of control population.

Automated morphometric approaches are used to detect epileptogenic structural abnormalities in 3D MR images in adults, using the variance of a control population to obtain z-score maps in an individual patient. Due to the substantial changes the developing human brain undergoes, performing such analyses in children is challenging. This study investigated six features derived from high-resolution T1 datasets in four groups: normal children (1.5T or 3T data), normal clinical scans (3T data), and patients with structural brain lesions (3T data), with each n = 10. Normative control data were obtained from the NIH study on normal brain development (n = 401). We show that control group size substantially influences the captured variance, directly impacting the patient's z-scores. Interestingly, matching on gender does not seem to be beneficial, which was unexpected. Using data obtained at higher field scanners produces slightly different base rates of suprathreshold voxels, as does using clinically derived normal studies, suggesting a subtle but systematic effect of both factors. Two approaches for controlling suprathreshold voxels in a multidimensional approach (combining features and requiring a minimum cluster size) were shown to be substantial and effective in reducing this number. Finally, specific strengths and limitations of such an approach could be demonstrated in individual cases.

Optimized simultaneous ASL and BOLD functional imaging of the whole brain.

PURPOSE: To compare a double-excitation combined arterial-spin labeling/blood-oxygenation level dependent (ASL/BOLD) functional imaging method to a double-echo method. ASL provides a useful complement to standard BOLD functional imaging, to map effects of cerebral hemodynamics. Whole-brain imaging is necessary to properly characterize large functional networks. A challenge of whole-brain ASL/BOLD is that images for ASL functional contrast must be acquired before significant longitudinal relaxation of the inverted spins occurs; however, a longer echo time (TE) is required for optimal BOLD functional contrast, lengthening the acquisition time. Thus, existing combined ASL/BOLD studies have only partial-brain coverage. MATERIALS AND METHODS: The proposed method allows acquisition of images for ASL contrast within a short period after the ASL labeling pulse and postinversion delay, then subsequent acquisition of images with longer TE for BOLD contrast. The technique is demonstrated using a narrative comprehension task in 35 normal children, and the double-excitation method is empirically compared with the double-echo method in 7 normal adults. RESULTS: Compared with a double-echo sequence, simulations show the double-excitation method improves ASL contrast-to-noise ratio (CNR) (∼50%) in later-acquired slices with minimal (<1%) reduction in BOLD CNR in earlier-acquired slices if reduced excitation flip angles for the ASL acquisitions are used. Empirical results from adult data are in agreement with the simulations. Group analyses from the narrative comprehension task also show greater intersubject sensitivity in BOLD versus ASL. CONCLUSION: Our method simultaneously optimizes ASL and BOLD acquisitions for CNR while economizing acquisition time.

Differences in paracingulate connectivity associated with epileptiform discharges and uncontrolled seizures in genetic generalized epilepsy.

OBJECTIVE: Patients with genetic generalized epilepsy (GGE) frequently continue to have seizures despite appropriate clinical management. GGE is associated with changes in the resting-state networks modulated by clinical factors such as duration of disease and response to treatment. However, the effect of generalized spike and wave discharges (GSWDs) and/or seizures on resting-state functional connectivity (RSFC) is not well understood. METHODS: We investigated the effects of GSWD frequency (in GGE patients), GGE (patients vs. healthy controls), and seizures (uncontrolled vs. controlled) on RSFC using seed-based voxel correlation in simultaneous electroencephalography (EEG) and resting-state functional magnetic resonance imaging (fMRI) (EEG/fMRI) data from 72 GGE patients (23 with uncontrolled seizures) and 38 healthy controls. We used seeds in paracingulate cortex, thalamus, cerebellum, and posterior cingulate cortex to examine changes in cortical-subcortical resting-state networks and the default mode network (DMN). We excluded from analyses time points surrounding GSWDs to avoid possible contamination of the resting state. RESULTS: (1) Higher frequency of GSWDs was associated with an increase in seed-based voxel correlation with cortical and subcortical brain regions associated with executive function, attention, and the DMN; (2) RSFC in patients with GGE, when compared to healthy controls, was increased between paracingulate cortex and anterior, but not posterior, thalamus; and (3) GGE patients with uncontrolled seizures exhibited decreased cerebellar RSFC. SIGNIFICANCE: Our findings in this large sample of patients with GGE (1) demonstrate an effect of interictal GSWDs on resting-state networks, (2) provide evidence that different thalamic nuclei may be affected differently by GGE, and (3) suggest that cerebellum is a modulator of ictogenic circuits.

Factors determining success of awake and asleep magnetic resonance imaging scans in nonsedated children.

Effective techniques that allow children to complete magnetic resonance imaging (MRI) scans without sedation are high priority for the imaging community. We used behavioral approaches to scan 64 sleeping infants and toddlers younger than 4 years, and 156 awake children aged 2.5 to 18 years, for a neuroimaging research protocol. Infants and their families participated in a desensitization protocol for several days, then scanning was performed at the child's bedtime during natural sleep. For awake young children, a behavioral protocol was used that included tangible reinforcers, exploration of the scanner environment and a brief practice session. Two scan sessions were targeted for awake children. Success rates by participant were quantified in terms of the proportion of requisite scans in each session that were successfully acquired. The average success rate in sleeping infants and toddlers was 0.461. For awake children aged 2.5 to 6 years, success rates for each session were 0.739 and 0.847. For children aged 7 years and older, success rates were over 0.900 for both the sessions. Overall, though success was lower later in a scan session for both sleeping infants and awake young children, our results demonstrate that it is feasible to collect high-quality imaging data using standard imaging sequences in infants and children without sedation.