Validating the association between brain activity, as measured in functional MRI, with a combination or a contrast of tasks is usually performed by replicating an experiment in a small group of subjects, and by assessing the presence of a statistically significant average effect across subjects (random effects analyses). While many efforts have been made to control the rate of false detections, statistical characteristics of the data have rarely been studied, and the reliability of the results (supra-thresholds areas that are considered as activated regions) has rarely been assessed. In this work, we take advantage of the large cohort of subjects who underwent the Localizer experiment to study the statistical nature of group data, propose some measures of the reliability of group studies, and address simple methodological questions as : is there, from the point of view of reliability, an optimal statistical threshold for activity maps ? How many subjects should be included in group studies ? What method should be preferred for inference ? Our results suggest that i) optimal thresholds can indeed be found, and are rather lower than usual corrected for multiple comparison thresholds ii) 20 subjects or more should be included in functional neuroimaging studies in order to have sufficient reliability, iii) non-parametric significance assessment should be preferred to parametric methods iv) cluster-level thresholding is more reliable than voxel-based thresholding v) mixed effects tests are much more reliable than random effects tests. Moreover, our study shows that inter-subject variability plays a prominent role in the relatively low sensitivity and reliability of group studies.

We examined the functional organization of cerebral activity in 3-month-old infants when they were listening to their mother language. Short sentences were presented in a slow event-related functional MRI paradigm. We then parsed the infant's network of perisylvian responsive regions into functionally distinct regions based on their speed of activation and sensitivity to sentence repetition. An adult-like structure of functional MRI response delays was observed along the superior temporal regions, suggesting a hierarchical processing scheme. The fastest responses were recorded in the vicinity of Heschl's gyrus, whereas responses became increasingly slower toward the posterior part of the superior temporal gyrus and toward the temporal poles and inferior frontal regions (Broca's area). Activation in the latter region increased when the sentence was repeated after a 14-s delay, suggesting the early involvement of Broca's area in verbal memory. The fact that Broca's area is active in infants before the babbling stage implies that activity in this region is not the consequence of sophisticated motor learning but, on the contrary, that this region may drive, through interactions with the perceptual system, the learning of the complex motor sequences required for future speech production. Our results point to a complex, hierarchical organization of the human brain in the first months of life, which may play a crucial role in language acquisition in our species.o what extent is the human species predisposed to acquire language? This question is generally debated by comparing the complexity of the speech input with infants' limited processing resources. Infants face the complex problem of being confronted with a continuous auditory signal that they should learn to segment into phonemes, syllables, words, and constituents and combine to understand and produce new information. Because language acquisition is fast, proceeds through a series of reproducible stages, and exhibits a systematicity that seems to go beyond what could possibly be learned from surrounding speech inputs, some researchers have postulated a special-purpose language acquisition device (1). However, infants' capacity of statistical learning (2) combined with the observation that speech possess numerous regularities have strengthened a constructivist view according to which the infant brain progressively extracts regularities in its environmental inputs (3).In most adults, speech processing relies on a hierarchy of well defined areas centered around the left sylvian fissure. Why does language processing systematically call on those regions? Do they possess special properties that can explain language emergence in humans? Examination of their initial functional organization in the first year of life may ultimately clarify how infants take advantage of their environment to achieve the linguistic sophistication of adults. Thanks to the development of noninvasive brain imaging, we can begin to decipher the cerebral resources at infants' disposal to process s...

Delivery of therapeutic or diagnostic agents to the brain is majorly hindered by the blood-brain barrier (BBB). Recently, many studies have demonstrated local and transient disruption of the BBB using low power ultrasound sonication combined with intravascular microbubbles. However, BBB opening and closure mechanisms are poorly understood, especially the maximum gap that may be safely generated between endothelial cells and the duration of opening of the BBB. Here, we studied BBB opening and closure under magnetic resonance (MR) guidance in a rat model. First, MR contrast agents (CA) of different hydrodynamic diameters (1 to 65 nm) were employed to estimate the largest molecular size permissible across the cerebral tissues. Second, to estimate the duration of the BBB opening, the CA were injected at various times post-BBB disruption (12 minutes to 24 hours). A T 1 mapping strategy was developed to assess CA concentration at the ultrasound (US) focal point. Based on our experimental data and BBB closure modeling, a calibration curve was obtained to compute the half closure time as a function of CA hydrodynamic diameter. These findings and the model provide an invaluable basis for optimal design and delivery of nanoparticles to the brain.

Background: Although cognitive processes such as reading and calculation are associated with reproducible cerebral networks, inter-individual variability is considerable. Understanding the origins of this variability will require the elaboration of large multimodal databases compiling behavioral, anatomical, genetic and functional neuroimaging data over hundreds of subjects. With this goal in mind, we designed a simple and fast acquisition procedure based on a 5-minute functional magnetic resonance imaging (fMRI) sequence that can be run as easily and as systematically as an anatomical scan, and is therefore used in every subject undergoing fMRI in our laboratory. This protocol captures the cerebral bases of auditory and visual perception, motor actions, reading, language comprehension and mental calculation at an individual level.