Maxime Taquet

Brain functional networks in syndromic and non-syndromic autism: a graph theoretical study of EEG connectivity

BackgroundGraph theory has been recently introduced to characterize complex brain networks, making it highly suitable to investigate altered connectivity in neurologic disorders. A current model proposes autism spectrum disorder (ASD) as a developmental disconnection syndrome, supported by converging evidence in both non-syndromic and syndromic ASD. However, the effects of abnormal connectivity on network properties have not been well studied, particularly in syndromic ASD. To close this gap, brain functional networks of electroencephalographic (EEG) connectivity were studied through graph measures in patients with Tuberous Sclerosis Complex (TSC), a disorder with a high prevalence of ASD, as well as in patients with non-syndromic ASD.MethodsEEG data were collected from TSC patients with ASD (n = 14) and without ASD (n = 29), from patients with non-syndromic ASD (n = 16), and from controls (n = 46). First, EEG connectivity was characterized by the mean coherence, the ratio of inter- over intra-hemispheric coherence and the ratio of long- over short-range coherence. Next, graph measures of the functional networks were computed and a resilience analysis was conducted. To distinguish effects related to ASD from those related to TSC, a two-way analysis of covariance (ANCOVA) was applied, using age as a covariate.ResultsAnalysis of network properties revealed differences specific to TSC and ASD, and these differences were very consistent across subgroups. In TSC, both with and without a concurrent diagnosis of ASD, mean coherence, global efficiency, and clustering coefficient were decreased and the average path length was increased. These findings indicate an altered network topology. In ASD, both with and without a concurrent diagnosis of TSC, decreased long- over short-range coherence and markedly increased network resilience were found.ConclusionsThe altered network topology in TSC represents a functional correlate of structural abnormalities and may play a role in the pathogenesis of neurological deficits. The increased resilience in ASD may reflect an excessively degenerate network with local overconnection and decreased functional specialization. This joint study of TSC and ASD networks provides a unique window to common neurobiological mechanisms in autism.

Characterizing brain tissue by assessment of the distribution of anisotropic microstructural environments in diffusion-compartment imaging (DIAMOND)

To develop a statistical model for the tridimensional diffusion MRI signal at each voxel that describes the signal arising from each tissue compartment in each voxel.

A Mathematical Framework for the Registration and Analysis of Multi-Fascicle Models for Population Studies of the Brain Microstructure

Diffusion tensor imaging (DTI) is unable to represent the diffusion signal arising from multiple crossing fascicles and freely diffusing water molecules. Generative models of the diffusion signal, such as multi-fascicle models, overcome this limitation by providing a parametric representation for the signal contribution of each population of water molecules. These models are of great interest in population studies to characterize and compare the brain microstructural properties. Central to population studies is the construction of an atlas and the registration of all subjects to it. However, the appropriate definition of registration and atlasing methods for multi-fascicle models have proven challenging. This paper proposes a mathematical framework to register and analyze multi-fascicle models. Specifically, we define novel operators to achieve interpolation, smoothing and averaging of multi-fascicle models. We also define a novel similarity metric to spatially align multi-fascicle models. Our framework enables simultaneous comparisons of different microstructural properties that are confounded in conventional DTI. The framework is validated on multi-fascicle models from 24 healthy subjects and 38 patients with tuberous sclerosis complex, 10 of whom have autism. We demonstrate the use of the multi-fascicle models registration and analysis framework in a population study of autism spectrum disorder.

Reliable selection of the number of fascicles in diffusion images by estimation of the generalization error

A number of diffusion models have been proposed to overcome the limitations of diffusion tensor imaging (DTI) which cannot represent multiple fascicles with heterogeneous orientations at each voxel. Among them, generative models such as multi-tensor models, CHARMED or NODDI represent each fascicle with a parametric model and are of great interest to characterize and compare white matter properties. However, the identification of the appropriate model, and particularly the estimation of the number of fascicles, has proven challenging. In this context, different model selection approaches have been proposed to identify the number of fascicles at each voxel. Most approaches attempt to maximize the quality of fit while penalizing complex models to avoid overfitting. However, the choice of a penalization strategy and the trade-off between penalization and quality of fit are rather arbitrary and produce highly variable results. In this paper, we propose for the first time to determine the number of fascicles at each voxel by assessing the generalization error. This criterion naturally prevents overfitting by comparing how the models predict new data not included in the model estimation. Since the generalization error cannot be directly computed, we propose to estimate it by the 632 bootstrap technique which has low bias and low variance. Results on synthetic phantoms and in vivo data show that our approach performs better than existing techniques, and is robust to the choice of decision threshold. Together with generative models of the diffusion signal, this technique will enable accurate identification of the model complexity at each voxel and accurate assessment of the white matter characteristics.

Greater widespread functional connectivity of the caudate in older adults who practice kripalu yoga and vipassana meditation than in controls

There has been a growing interest in understanding how contemplative practices affect brain functional organization. However, most studies have restricted their exploration to predefined networks. Furthermore, scientific comparisons of different contemplative traditions are largely lacking. Here we explored differences in whole brain resting state functional connectivity between experienced yoga practitioners, experienced meditators, and matched controls. Analyses were repeated in an independent sample of experienced meditators and matched controls. Analyses utilizing Network-Based Statistics (Zalesky et al., 2010) revealed difference components for yoga practitioners > controls and meditators > controls in which the right caudate was a central node. Follow up analyses revealed that yoga practitioners and meditators had significantly greater degree centrality in the caudate than controls. This greater degree centrality was not driven by single connections but by greater connectivity between the caudate and numerous brain regions. Findings of greater caudate connectivity in meditators than in controls was replicated in an independent dataset. These findings suggest that yoga and meditation practitioners have stronger functional connectivity within basal ganglia cortico-thalamic feedback loops than non-practitioners. Although we could not provide evidence for its mechanistic role, this greater connectivity might be related to the often reported effects of meditation and yoga on behavioral flexibility, mental health, and well-being.

Characterizing the DIstribution of Anisotropic MicrO-structural eNvironments with Diffusion-Weighted Imaging (DIAMOND)

Diffusion-weighted imaging (DWI) enables investigation of the brain microstructure by probing natural barriers to diffusion in tissues. In this work, we propose a novel generative model of the DW signal based on considerations of the tissue microstructure that gives rise to the diffusion attenuation. We consider that the DW signal can be described as the sum of a large number of individual homogeneous spin packets, each of them undergoing local 3-D Gaussian diffusion represented by a diffusion tensor. We consider that each voxel contains a number of large scale microstructural environments and describe each of them via a matrix-variate Gamma distribution of spin packets. Our novel model of DIstribution of Anisotropic MicrOstructural eNvironments in DWI (DIAMOND) is derived from first principles. It enables characterization of the extra-cellular space, of each individual white matter fascicle in each voxel and provides a novel measure of the microstructure heterogeneity. We determine the number of fascicles at each voxel with a novel model selection framework based upon the minimization of the generalization error. We evaluate our approach with numerous in-vivo experiments, with cross-testing and with pathological DW-MRI. We show that DIAMOND may provide novel biomarkers that captures the tissue integrity.

Registration and analysis of white matter group differences with a multi-fiber model.

Diffusion magnetic resonance imaging has been used extensively to probe the white matter in vivo. Typically, the raw diffusion images are used to reconstruct a diffusion tensor image (DTI). The incapacity of DTI to represent crossing fibers leaded to the development of more sophisticated diffusion models. Among them, multi-fiber models represent each fiber bundle independently, allowing the direct extraction of diffusion features for population analysis. However, no method exists to properly register multi-fiber models, seriously limiting their use in group comparisons. This paper presents a registration and atlas construction method for multi-fiber models. The validity of the registration is demonstrated on a dataset of 45 subjects, including both healthy and unhealthy subjects. Morphometry analysis and tract-based statistics are then carried out, proving that multi-fiber models registration is better at detecting white matter local differences than single tensor registration.

Emotions in Everyday Life.

Despite decades of research establishing the causes and consequences of emotions in the laboratory, we know surprisingly little about emotions in everyday life. We developed a smartphone application that monitored real-time emotions of an exceptionally large (N = 11,000+) and heterogeneous participants sample. People’s everyday life seems profoundly emotional: participants experienced at least one emotion 90% of the time. The most frequent emotion was joy, followed by love and anxiety. People experienced positive emotions 2.5 times more often than negative emotions, but also experienced positive and negative emotions simultaneously relatively frequently. We also characterized the interconnections between people’s emotions using network analysis. This novel approach to emotion research suggests that specific emotions can fall into the following categories 1) connector emotions (e.g., joy), which stimulate same valence emotions while inhibiting opposite valence emotions, 2) provincial emotions (e.g., gratitude), which stimulate same valence emotions only, or 3) distal emotions (e.g., embarrassment), which have little interaction with other emotions and are typically experienced in isolation. Providing both basic foundations and novel tools to the study of emotions in everyday life, these findings demonstrate that emotions are ubiquitous to life and can exist together and distinctly, which has important implications for both emotional interventions and theory.

Tubers are neither static nor discrete Evidence from serial diffusion tensor imaging

Objective: To assess the extent and evolution of tissue abnormality of tubers, perituber tissue, and normal-appearing white matter (NAWM) in patients with tuberous sclerosis complex using serial diffusion tensor imaging. Methods: We applied automatic segmentation based on a combined global-local intensity mixture model of 3T structural and 35 direction diffusion tensor MRIs (diffusion tensor imaging) to define 3 regions: tuber tissue, an equal volume perituber rim, and the remaining NAWM. For each patient, scan, lobe, and tissue type, we analyzed the averages of mean diffusivity (MD) and fractional anisotropy (FA) in a generalized additive mixed model. Results: Twenty-five patients (mean age 5.9 years; range 0.5–24.5 years) underwent 2 to 6 scans each, totaling 70 scans. Average time between scans was 1.2 years (range 0.4–2.9). Patient scans were compared with those of 73 healthy controls. FA values were lowest, and MD values were highest in tubers, next in perituber tissue, then in NAWM. Longitudinal analysis showed a positive (FA) and negative (MD) correlation with age in tubers, perituber tissue, and NAWM. All 3 tissue types followed a biexponential developmental trajectory, similar to the white matter of controls. An additional qualitative analysis showed a gradual transition of diffusion values across the tissue type boundaries. Conclusions: Similar to NAWM, tuber and perituber tissues in tuberous sclerosis complex undergo microstructural evolution with age. The extent of diffusion abnormality decreases with distance to the tuber, in line with known extension of histologic, immunohistochemical, and molecular abnormalities beyond tuber pathology.

Spatially adaptive log-euclidean polyaffine registration based on sparse matches

Log-euclidean polyaffine transforms have recently been introduced to characterize the local affine behavior of the deformation in principal anatomical structures. The elegant mathematical framework makes them a powerful tool for image registration. However, their application is limited to large structures since they require the pre-definition of affine regions. This paper extends the polyaffine registration to adaptively fit a log-euclidean polyaffine transform that captures deformations at smaller scales. The approach is based on the sparse selection of matching points in the images and the formulation of the problem as an expectation maximization iterative closest point problem. The efficiency of the algorithm is shown through experiments on inter-subject registration of brain MRI between a healthy subject and patients with multiple sclerosis.