The relationship between frontotemporal effective connectivity during picture naming, behavior, and preserved cortical tissue in chronic aphasia

NIH National Institute on Deafness and Other Communication Disorders (NIDCD) grant 1P50DC01228

Changes in task-based effective connectivity in language networks following rehabilitation in post-stroke patients with aphasia

In this study, we examined regions in the left and right hemisphere language network that were altered in terms of the underlying neural activation and effective connectivity subsequent to language rehabilitation. Eight persons with chronic post-stroke aphasia and eight normal controls participated in the current study. Patients received a 10 week semantic feature-based rehabilitation program to improve their skills. Therapy was provided on atypical examples of one trained category while two control categories were monitored; the categories were counterbalanced across patients. In each fMRI session, two experimental tasks were conducted: (a) picture naming and (b) semantic feature verification of trained and untrained categories. Analysis of treatment effect sizes revealed that all patients showed greater improvements on the trained category relative to untrained categories. Results from this study show remarkable patterns of consistency despite the inherent variability in lesion size and activation patterns across patients. Across patients, activation that emerged as a function of rehabilitation on the trained category included bilateral IFG, bilateral SFG, LMFG, and LPCG for picture naming; and bilateral IFG, bilateral MFG, LSFG, and bilateral MTG for semantic feature verification. Analysis of effective connectivity using Dynamic Causal Modeling (DCM) indicated that LIFG was the consistently significantly modulated region after rehabilitation across participants. These results indicate that language networks in patients with aphasia resemble normal language control networks and that this similarity is accentuated by rehabilitation.The funding for this project comes from NIDCD/NIH 1P50DC012283 and NIDCD/NIH 1K18DC011517. (1P50DC012283 - NIDCD/NIH; 1K18DC011517 - NIDCD/NIH)Published versio

Improved brain growth and microstructural development in breast milk-fed very low birth weight premature infants.

AIM: Breast milk feeding is linked to improved neurodevelopmental outcomes in very low birth weight (VLBW) infants, though the mechanisms are not well understood. This study utilised quantitative magnetic resonance imaging (qMRI) techniques to compare brain growth and white matter development in preterm infants receiving primarily breast milk versus formula feeds. METHODS: We prospectively enrolled infants born at very low birth weight (<1500 g) and <32 weeks gestational age and performed MRI at term-equivalent age. We utilised volumetric segmentation to calculate regional and total brain volumes and diffusion tensor imaging to evaluate white matter microstructural organisation. Daily nutritional data were extracted from the medical record. RESULTS: Nutritional and MRI data were obtained for 68 infants admitted within the first week of life (44 breast milk and 24 formula). Breast milk–fed infants demonstrated significantly larger total brain volumes (P = .04) as well as volumes in the amygdala-hippocampus and cerebellum (P < .01) compared with formula-fed. Infants receiving breast milk also demonstrated greater white matter microstructural organisation in the corpus callosum, posterior limb of internal capsule and cerebellum (P < .01 to .03). CONCLUSIONS: VLBW infants receiving primarily breast milk versus preterm formula in this small exploratory study demonstrated significantly greater regional brain volumes and white matter microstructural organisation by term-equivalent age

Hemodynamic Responses of the Placenta and Brain to Maternal Hyperoxia in Fetuses with Congenital Heart Disease by Using Blood Oxygen-Level Dependent MRI.

Background Impaired brain development in fetuses with congenital heart disease (CHD) may result from inadequate cerebral oxygen supply in utero. Purpose To test whether fetal cerebral oxygenation can be increased by maternal oxygen administration, effects of maternal hyperoxia on blood oxygenation of the placenta and fetal brain were examined by using blood oxygenation level-dependent (BOLD) functional MRI. Materials and Methods In this prospective study, BOLD MRI was performed in 86 fetuses (56 healthy fetuses and 30 fetuses diagnosed with CHD) between 22 and 39 weeks gestational age (GA) from May 2015 to December 2017, with the following study design: phase I, 2-minute resting state at baseline (room air); phase II, 6-minute maternal hyperoxia with 100% oxygen; and phase III, 5.6-minute return to resting state. After motion correction, the signals were averaged over the placenta and fetal brain and converted to the change in R2* (ΔR2*). Fetuses with CHD were categorized into those with a single ventricle (SV) or two ventricles (TVs) and those with aortic obstruction (AO) or non-AO. Data were analyzed by using generalized linear mixed models controlling for GA and sex. Results Placental ΔR2* increased during maternal hyperoxia in healthy fetuses and fetuses with CHD, but it was higher in SV CHD (mean ΔR2*, 1.3 sec-1 ± 0.1 [standard error; P &lt; .01], 1.9 sec-1 ± 0.2 [P &lt; .01], and 1.0 sec-1 ± 0.3 [P &lt; .01], respectively, for control fetuses, fetuses with SV CHD, and fetuses with TV CHD). Placental ΔR2* during maternal hyperoxia changed with GA in healthy control fetuses and fetuses with SV or AO CHD (ΔR2* per week, 0.1 sec-1 ± 0 [P &lt; .01], 0.2 sec-1 ± 0 [P = .01], and 0.2 sec-1 ± 0 [P = .01], respectively), but not in fetuses with CHD and TV or non-AO. Fetal brain ΔR2* was constant across all phases in healthy control fetuses and fetuses with TV CHD but increased during maternal hyperoxia in fetuses with SV or AO CHD (mean ΔR2*, 0.7 sec-1 ± 0.2 [P = .01] and 0.5 sec-1 ± 0.2 [P = .02], respectively). Conclusion Six minutes of maternal hyperoxia increased placental oxygenation in healthy fetuses and fetuses with congenital heart disease, and it selectively increased cerebral blood oxygenation in fetuses with single ventricle or aortic obstruction. © RSNA, 2019 Online supplemental material is available for this article

Feasibility of QSM in the human placenta

© 2020 International Society for Magnetic Resonance in Medicine Purpose: Quantitative susceptibility mapping (QSM) is an emerging tool for the precise characterization of human tissue, including regional oxygenation. A critical function of the human placenta is oxygen transfer to the developing fetus, which remains difficult to study in utero. The purpose of this study is to investigate the feasibility of performing QSM in the human placenta in utero. Methods: In healthy pregnant women, 3D gradient echo data of the placenta were acquired with prospective respiratory gating at 1.5 Tesla and 3 Tesla. A brief period (6-7 min) of maternal hyperoxia was induced to increase placental oxygenation in a subset of women scanned at 3 Tesla, and data were acquired before and during oxygen administration. Susceptibility and (Formula presented.) / (Formula presented.) maps were reconstructed from gradient echo data, and mean and SD of these measures within the whole placenta were calculated. Results: A total of 54 women were studied at a mean gestational age of 30.7 ± 4.2 (range: 24 5/7-38 4/7) weeks. Susceptibility and (Formula presented.) maps demonstrated lobular contrast reflecting regional oxygenation difference at both field strengths. SD of susceptibilities, mean (Formula presented.), and SD of (Formula presented.) of the placenta showed a linear relationship with gestational age (P \u3c.01 for all). These measures were also responsive to maternal hyperoxia, and there was an increasing response with advancing gestational age (P \u3c.01 for all). Conclusion: This study demonstrates the feasibility of performing placental QSM in pregnant women and supports the potential for placental QSM to provide noninvasive in vivo assessment of placental oxygenation

Third Trimester Cerebellar Metabolite Concentrations are Decreased in Very Premature Infants with Structural Brain Injury.

Abstract Advanced neuroimaging techniques have improved our understanding of microstructural changes in the preterm supratentorial brain as well as the cerebellum and its association with impaired neurodevelopmental outcomes. However, the metabolic interrogation of the developing cerebellum during the early postnatal period after preterm birth remains largely unknown. Our study investigates the relationship between cerebellar neurometabolites measured by proton magnetic spectroscopy (1H-MRS) in preterm infants with advancing post-menstrual age (PMA) and brain injury during ex-utero third trimester prior to term equivalent age (TEA). We prospectively enrolled and acquired high quality 1H-MRS at median 33.0 (IQR 31.6–35.2) weeks PMA from a voxel placed in the cerebellum of 53 premature infants born at a median gestational age of 27.0 (IQR 25.0–29.0) weeks. 1H-MRS data were processed using LCModel software to calculate absolute metabolite concentrations of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr). We noted positive correlations of cerebellar concentrations of NAA, Cho and Cr (Spearman correlations of 0.59, 0.64 and 0.52, respectively, p value < 0.0001) and negative correlation of Cho/Cr ratio (R −0.5, p value 0.0002) with advancing PMA. Moderate-to-severe cerebellar injury was noted on conventional magnetic resonance imaging (MRI) in 14 (26.4%) of the infants and were noted to have lower cerebellar NAA, Cho and Cr concentrations compared with those without injury (p value < 0.001). Several clinical complications of prematurity including necrotizing enterocolitis, systemic infections and bronchopulmonary dysplasia were associated with altered metabolite concentrations in the developing cerebellum. We report for the first time that ex-utero third trimester cerebellar metabolite concentrations are decreased in very preterm infants with moderate-to-severe structural cerebellar injury. We report increasing temporal trends of metabolite concentrations in the cerebellum with advancing PMA, which was impaired in infants with brain injury on MRI and may have early diagnostic and prognostic value in predicting neurodevelopmental outcomes in very preterm infants

Feasibility of QSM in the human placenta.

© 2020 International Society for Magnetic Resonance in Medicine Purpose: Quantitative susceptibility mapping (QSM) is an emerging tool for the precise characterization of human tissue, including regional oxygenation. A critical function of the human placenta is oxygen transfer to the developing fetus, which remains difficult to study in utero. The purpose of this study is to investigate the feasibility of performing QSM in the human placenta in utero. Methods: In healthy pregnant women, 3D gradient echo data of the placenta were acquired with prospective respiratory gating at 1.5 Tesla and 3 Tesla. A brief period (6-7 min) of maternal hyperoxia was induced to increase placental oxygenation in a subset of women scanned at 3 Tesla, and data were acquired before and during oxygen administration. Susceptibility and (Formula presented.) / (Formula presented.) maps were reconstructed from gradient echo data, and mean and SD of these measures within the whole placenta were calculated. Results: A total of 54 women were studied at a mean gestational age of 30.7 ± 4.2 (range: 24 5/7-38 4/7) weeks. Susceptibility and (Formula presented.) maps demonstrated lobular contrast reflecting regional oxygenation difference at both field strengths. SD of susceptibilities, mean (Formula presented.), and SD of (Formula presented.) of the placenta showed a linear relationship with gestational age (P \u3c.01 for all). These measures were also responsive to maternal hyperoxia, and there was an increasing response with advancing gestational age (P \u3c.01 for all). Conclusion: This study demonstrates the feasibility of performing placental QSM in pregnant women and supports the potential for placental QSM to provide noninvasive in vivo assessment of placental oxygenation

Impaired in vivo feto-placental development is associated with neonatal neurobehavioral outcomes

BACKGROUND: Fetal growth restriction (FGR) is a risk factor for neurodevelopmental problems, yet remains poorly understood. We sought to examine the relationship between intrauterine development and neonatal neurobehavior in pregnancies diagnosed with antenatal FGR. METHODS: We recruited women with singleton pregnancies diagnosed with FGR and measured placental and fetal brain volumes using MRI. NICU Network Neurobehavioral Scale (NNNS) assessments were performed at term equivalent age. Associations between intrauterine volumes and neurobehavioral outcomes were assessed using generalized estimating equation models. RESULTS: We enrolled 44 women diagnosed with FGR who underwent fetal MRI and 28 infants underwent NNNS assessments. Placental volumes were associated with increased self-regulation and decreased excitability; total brain, brainstem, cortical and subcortical gray matter (SCGM) volumes were positively associated with higher self-regulation; SCGM also was positively associated with higher quality of movement; increasing cerebellar volumes were positively associated with attention, decreased lethargy, non-optimal reflexes and need for special handling; brainstem volumes also were associated with decreased lethargy and non-optimal reflexes; cerebral and cortical white matter volumes were positively associated with hypotonicity. CONCLUSION: Disrupted intrauterine growth in pregnancies complicated by antenatally diagnosed FGR is associated with altered neonatal neurobehavior. Further work to determine long-term neurodevelopmental impacts is warranted. IMPACT: Fetal growth restriction is a risk factor for adverse neurodevelopment, but remains difficult to accurately identify. Intrauterine brain volumes are associated with infant neurobehavior. The antenatal diagnosis of fetal growth restriction is a risk factor for abnormal infant neurobehavior

Examining the relationship between fetal cortical thickness, gestational age, and maternal psychological distress

In utero exposure to maternal stress, anxiety, and depression has been associated with reduced cortical thickness (CT), and CT changes, in turn, to adverse neuropsychiatric outcomes. Here, we investigated global and regional (G/RCT) changes associated with fetal exposure to maternal psychological distress in 265 brain MRI studies from 177 healthy fetuses of low-risk pregnant women. GCT was measured from cortical gray matter (CGM) voxels; RCT was estimated from 82 cortical regions. GCT and RCT in 87% of regions strongly correlated with GA. Fetal exposure was most strongly associated with RCT in the parahippocampal region, ventromedial prefrontal cortex, and supramarginal gyrus suggesting that cortical alterations commonly associated with prenatal exposure could emerge in-utero. However, we note that while regional fetal brain involvement conformed to patterns observed in newborns and children exposed to prenatal maternal psychological distress, the reported associations did not survive multiple comparisons correction. This could be because the effects are more subtle in this early developmental window or because majority of the pregnant women in our study did not experience high levels of maternal distress. It is our hope that the current findings will spur future hypothesis-driven studies that include a full spectrum of maternal mental health scores