François Lazeyras

Early alteration of structural and functional brain development in premature infants born with intrauterine growth restriction.

Placental insufficiency with fetal intrauterine growth restriction (IUGR) is an important cause of perinatal mortality and morbidity and is subsequently associated with significant neurodevelopmental impairment in cognitive function, attention capacity, and school performance. The underlying biologic cause for this association is unclear. Twenty-eight preterm infants (gestational age 32.5 ± 1.9 wk) were studied by early and term magnetic resonance imaging (MRI). An advanced quantitative volumetric three-dimensional MRI technique was used to measure brain tissue volumes in 14 premature infants with placental insufficiency, defined by abnormal antenatal Doppler measurements and mean birth weights <10th percentile (1246 ± 299 g) (IUGR) and in 14 preterm infants matched for gestational age with normal mean birth weights 1843 ± 246 g (control). Functional outcome was measured at term in all infants by a specialized assessment scale of preterm infant behavior. Premature infants with IUGR had a significant reduction in intracranial volume (mean ± SD: 253.7 ± 29.9 versus 300.5 ± 43.5 mL, p < 0.01) and in cerebral cortical gray matter (mean ± SD: 77.2 ± 16.3 versus 106.8 ± 24.6 mL, p < 0.01) when measured within the first 2 wk of life compared with control premature infants. These findings persisted at term with intracranial volume (mean ± SD: 429.3 ± 47.9 versus 475.9 ± 53.4 mL, p < 0.05) and cerebral cortical gray matter (mean ± SD: 149.3 ± 29.2 versus 189 ± 34.2 mL, p < 0.01). Behavioral assessment at term showed a significantly less mature score in the subsystem of attention-interaction availability in IUGR infants (p ± 0.01). Cerebral cortical gray matter volume at term correlated with attention-interaction capacity measured at term (r = 0.45, p < 0.05). These results suggest that placental insufficiency with IUGR have specific structural and functional consequences on cerebral cortical brain development. These findings may provide insight into the structural-functional correlate for the developmental deficits associated with IUGR.

Primary cortical folding in the human newborn: an early marker of later functional development.

In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26-36 weeks of gestational age), and defined early endophenotypes of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infants behaviour (APIB).

A Surface-Based Approach to Quantify Local Cortical Gyrification

The high complexity of cortical convolutions in humans is very challenging both for engineers to measure and compare it, and for biologists and physicians to understand it. In this paper, we propose a surface-based method for the quantification of cortical gyrification. Our method uses accurate 3-D cortical reconstruction and computes local measurements of gyrification at thousands of points over the whole cortical surface. The potential of our method to identify and localize precisely gyral abnormalities is illustrated by a clinical study on a group of children affected by 22q11 Deletion Syndrome, compared to control individuals.

Non-invasive epileptic focus localization using EEG-triggered functional MRI and electromagnetic tomography

We present a new approach for non-invasive localization of focal epileptogenic discharges in patients considered for surgical treatment. EEG-triggered functional MR imaging (fMRI) and 3D EEG source localization were combined to map the primary electrical source with high spatial resolution. The method is illustrated by the case of a patient with medically intractable frontal lobe epilepsy. EEG obtained in the MRI system allowed triggering of the fMRI acquisition by the patients habitual epileptogenic discharges. fMRI revealed multiple areas of signal enhancement. Three-dimensional EEG source localization identified the same active areas and provided evidence of onset in the left frontal lobe. Subsequent electrocorticography from subdural electrodes confirmed spike and seizure onset over this region. This approach, i.e. the combination of EEG-triggered fMRI and 3D EEG source analysis, represents a promising additional tool for presurgical epilepsy evaluation allowing precise non-invasive identification of the epileptic foci.

Structural and functional brain development after hydrocortisone treatment for neonatal chronic lung disease

Objective. There is much concern about potential neurodevelopmental impairment after neonatal corticosteroid treatment for chronic lung disease. Dexamethasone is the corticosteroid most often used in this clinical setting, and it has been shown to impair cortical growth among preterm infants. This study evaluated long-term effects of prematurity itself and of neonatal hydrocortisone treatment on structural and functional brain development using three-dimensional MRI with advanced image-processing and neurocognitive assessments. Methods. Sixty children born preterm, including 25 children treated with hydrocortisone and 35 children not treated with hydrocortisone, and 21 children born at term were evaluated, at a mean age of 8 years, with quantitative MRI and neurocognitive assessments (Wechsler Intelligence Scales for Children-Revised [WISC-R]). Automatic image segmentation was used to determine the tissue volumes of cerebral gray matter, white matter, and cerebrospinal fluid. In addition, the volume of the hippocampus was determined manually. WISC-R scores were recorded as mean intelligence scores at evaluation. Neonatal hydrocortisone treatment for chronic lung disease consisted of a starting dose of 5 mg/kg per day tapered over a minimum of 3 weeks. Results. Cerebral gray matter volume was reduced among preterm children (regardless of hydrocortisone treatment), compared with children born at term (preterm: 649 ± 4.4 mL; term: 666 ± 7.3 mL). Birth weight was shown to correlate with gray matter volume at 8 years of age in the preterm group (r = 0.421). Cerebrospinal fluid volume was increased among children born preterm, compared with children born at term (preterm: 228 ± 4.9 mL; term: 206 ± 8.2 mL). Total hippocampal volume tended to be lower among children born preterm, with a more pronounced reduction of hippocampal volume among boys (preterm: 6.1 ± 0.13 mL; term: 6.56 ± 0.2 mL). The WISC-R score was lower for children born preterm, compared with children born at term (preterm: 99.4 ± 12.4; term: 109.6 ± 8.8). Children treated with neonatal hydrocortisone had very similar volumes of gray matter (preterm with hydrocortisone: 650 ± 7.0 mL; preterm without hydrocortisone: 640 ± 5.6 mL), white matter (preterm with hydrocortisone: 503 ± 6.1 mL; preterm without hydrocortisone: 510 ± 4.9 mL), and cerebrospinal fluid (preterm with hydrocortisone: 227 ± 7.4 mL; preterm without hydrocortisone: 224 ± 6.0 mL), compared with untreated infants. The hippocampal volumes were similar in the 2 groups (preterm with hydrocortisone: 5.92 ± 0.15 mL; preterm without hydrocortisone: 5.81 ± 0.12 mL). The WISC-R score assessments were within the normal range for both groups, with no difference between the groups (preterm with hydrocortisone: 100.8 ± 13; preterm without hydrocortisone: 98.6 ± 12.3). Conclusions. Prematurity is associated with mild brain structural differences that persist at 8 years of age, with associated lower scores in neurocognitive assessments. The data suggest that perinatal hydrocortisone given at the described dosage has no long-term effects on either neurostructural brain development or neurocognitive outcomes.

Intrauterine growth restriction affects the preterm infant's hippocampus

The hippocampus is known to be vulnerable to hypoxia, stress, and undernutrition, all likely to be present in fetal intrauterine growth restriction (IUGR). The effect of IUGR in preterm infants on the hippocampus was studied using 3D magnetic resonance imaging at term-equivalent age Thirteen preterm infants born with IUGR after placental insufficiency were compared with 13 infants with normal intrauterine growth age matched for gestational age. The hippocampal structural differences were defined using voxel-based morphometry and manual segmentation. The specific neurobehavioral function was evaluated by the Assessment of Preterm Infants Behavior at term and at 24 mo of corrected age by a Bayley Scales of Infant and Toddler Development. Voxel-based morphometry detected significant gray matter volume differences in the hippocampus between the two groups. This finding was confirmed by manual segmentation of the hippocampus with a reduction of hippocampal volume after IUGR. The hippocampal volume reduction was further associated with functional behavioral differences at term-equivalent age in all six subdomains of the Assessment of Preterm Infants Behavior but not at 24 mo of corrected age. We conclude that hippocampal development in IUGR is altered and might result from a combination of maternal corticosteroid hormone exposure, hypoxemia, and micronutrient deficiency.

Neural systems for orienting attention to the location of threat signals: an event-related fMRI study

Attention may reflexively shift towards the location of perceived threats, but it is still unclear how these spatial biases recruit the distributed fronto-parietal cortical networks involved in other aspects of selective attention. We used event-related fMRI to determine how brain responses to a neutral visual target are influenced by the emotional expression of faces appearing at the same location during a covert orienting task. On each trial, two faces were briefly presented, one in each upper visual field (one neutral and one emotional, fearful or happy), followed by a unilateral target (a small horizontal or vertical bar) replacing one of the faces. Participants had to discriminate the target orientation, shown on the same (valid) or opposite (invalid) side as the emotional face. Trials with faces but no subsequent target (cue-only trials) were included to disentangle activation due to emotional cues from their effects on target detection. We found increased responses in bilateral temporo-parietal areas and right occipito-parietal cortex for fearful faces relative to happy faces, unrelated to the subsequent target and cueing validity. More critically, we found a selective modulation of intraparietal and orbitofrontal cortex for targets following an invalid fearful face, as well as an increased visual response in right lateral occipital cortex for targets following a valid fearful face. No such effects were observed with happy faces. These results demonstrate that fearful faces can act as exogenous cues by increasing sensory processing in extrastriate cortex for a subsequent target presented at the same location, but also produce a cost in disengaging towards another location by altering the response of IPS to invalidly cued targets. Neural mechanisms responsible for orienting attention towards emotional vs. non-emotional stimuli are thus partly shared in parietal and visual areas, but also partly distinct.

View-independent coding of face identity in frontal and temporal cortices is modulated by familiarity: an event-related fMRI study

Face recognition is a unique visual skill enabling us to recognize a large number of person identities, despite many differences in the visual image from one exposure to another due to changes in viewpoint, illumination, or simply passage of time. Previous familiarity with a face may facilitate recognition when visual changes are important. Using event-related fMRI in 13 healthy observers, we studied the brain systems involved in extracting face identity independent of modifications in visual appearance during a repetition priming paradigm in which two different photographs of the same face (either famous or unfamiliar) were repeated at varying delays. We found that functionally defined face-selective areas in the lateral fusiform cortex showed no repetition effects for faces across changes in image views, irrespective of pre-existing familiarity, suggesting that face representations formed in this region do not generalize across different visual images, even for well-known faces. Repetition of different but easily recognizable views of an unfamiliar face produced selective repetition decreases in a medial portion of the right fusiform gyrus, whereas distinct views of a famous face produced repetition decreases in left middle temporal and left inferior frontal cortex selectively, but no decreases in fusiform cortex. These findings reveal that different views of the same familiar face may not be integrated within a single representation at initial perceptual stages subserved by the fusiform face areas, but rather involve later processing stages where more abstract identity information is accessed.

Validation of a patient-specific one-dimensional model of the systemic arterial tree

The aim of this study is to develop and validate a patient-specific distributed model of the systemic arterial tree. This model is built using geometric and hemodynamic data measured on a specific person and validated with noninvasive measurements of flow and pressure on the same person, providing thus a patient-specific model and validation. The systemic arterial tree geometry was obtained from MR angiographic measurements. A nonlinear viscoelastic constitutive law for the arterial wall is considered. Arterial wall distensibility is based on literature data and adapted to match the wave propagation velocity of the main arteries of the specific subject, which were estimated by pressure waves traveling time. The intimal shear stress is modeled using the Witzig-Womersley theory. Blood pressure is measured using applanation tonometry and flow rate using transcranial ultrasound and phase-contrast-MRI. The model predicts pressure and flow waveforms in good qualitative and quantitative agreement with the in vivo measurements, in terms of wave shape and specific wave features. Comparison with a generic one-dimensional model shows that the patient-specific model better predicts pressure and flow at specific arterial sites. These results obtained let us conclude that a patient-specific one-dimensional model of the arterial tree is able to predict well pressure and flow waveforms in the main systemic circulation, whereas this is not always the case for a generic one-dimensional model.

Portraits or People? Distinct Representations of Face Identity in the Human Visual Cortex

Humans can identify individual faces under different viewpoints, even after a single encounter. We determined brain regions responsible for processing face identity across view changes after variable delays with several intervening stimuli, using event-related functional magnetic resonance imaging during a long-term repetition priming paradigm. Unfamiliar faces were presented sequentially either in a frontal or three-quarter view. Each face identity was repeated once after an unpredictable lag, with either the same or another viewpoint. Behavioral data showed significant priming in response time, irrespective of view changes. Brain imaging results revealed a reduced response in the lateral occipital and fusiform cortex with face repetition. Bilateral face-selective fusiform areas showed view-sensitive repetition effects, generalizing only from three-quarter to front-views. More medial regions in the left (but not in the right) fusiform showed repetition effects across all types of viewpoint changes. These results reveal that distinct regions within the fusiform cortex hold view-sensitive or view-invariant traces of novel faces, and that face identity is represented in a view-sensitive manner in the functionally defined face-selective areas of both hemispheres. In addition, our finding of a better generalization after exposure to a 3/4-view than to a front-view demonstrates for the first time a neural substrate in the fusiform cortex for the common recognition advantage of three-quarter faces. This pattern provides new insights into the nature of face representation in the human visual system.