Diffusion imaging genomics provides novel insight into early mechanisms of cerebral small vessel disease.

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia. Genetic risk loci for white matter hyperintensities (WMH), the most common MRI-marker of cSVD in older age, were recently shown to be significantly associated with white matter (WM) microstructure on diffusion tensor imaging (signal-based) in young adults. To provide new insights into these early changes in WM microstructure and their relation with cSVD, we sought to explore the genetic underpinnings of cutting-edge tissue-based diffusion imaging markers across the adult lifespan. We conducted a genome-wide association study of neurite orientation dispersion and density imaging (NODDI) markers in young adults (i-Share study: N = 1 758, (mean[range]) 22.1[18-35] years), with follow-up in young middle-aged (Rhineland Study: N = 714, 35.2[30-40] years) and late middle-aged to older individuals (UK Biobank: N = 33 224, 64.3[45-82] years). We identified 21 loci associated with NODDI markers across brain regions in young adults. The most robust association, replicated in both follow-up cohorts, was with Neurite Density Index (NDI) at chr5q14.3, a known WMH locus in VCAN. Two additional loci were replicated in UK Biobank, at chr17q21.2 with NDI, and chr19q13.12 with Orientation Dispersion Index (ODI). Transcriptome-wide association studies showed associations of STAT3 expression in arterial and adipose tissue (chr17q21.2) with NDI, and of several genes at chr19q13.12 with ODI. Genetic susceptibility to larger WMH volume, but not to vascular risk factors, was significantly associated with decreased NDI in young adults, especially in regions known to harbor WMH in older age. Individually, seven of 25 known WMH risk loci were associated with NDI in young adults. In conclusion, we identified multiple novel genetic risk loci associated with NODDI markers, particularly NDI, in early adulthood. These point to possible early-life mechanisms underlying cSVD and to processes involving remyelination, neurodevelopment and neurodegeneration, with a potential for novel approaches to prevention.

Novel characterization of the relationship between verbal list-learning outcomes and hippocampal subfields in healthy adults.

The relationship between hippocampal subfield volumetry and verbal list-learning test outcomes have mostly been studied in clinical and elderly populations, and remain controversial. For the first time, we characterized a relationship between verbal list-learning test outcomes and hippocampal subfield volumetry on two large separate datasets of 447 and 1,442 healthy young and middle-aged adults, and explored the processes that could explain this relationship. We observed a replicable positive linear correlation between verbal list-learning test free recall scores and CA1 volume, specific to verbal list learning as demonstrated by the hippocampal subfield volumetry independence from verbal intelligence. Learning meaningless items was also positively correlated with CA1 volume, pointing to the role of the test design rather than word meaning. Accordingly, we found that association-based mnemonics mediated the relationship between verbal list-learning test outcomes and CA1 volume. This mediation suggests that integrating items into associative representations during verbal list-learning tests explains CA1 volume variations: this new explanation is consistent with the associative functions of the human CA1.

The MRi-Share database: brain imaging in a cross-sectional cohort of 1870 university students.

We report on MRi-Share, a multi-modal brain MRI database acquired in a unique sample of 1870 young healthy adults, aged 18-35 years, while undergoing university-level education. MRi-Share contains structural (T1 and FLAIR), diffusion (multispectral), susceptibility-weighted (SWI), and resting-state functional imaging modalities. Here, we described the contents of these different neuroimaging datasets and the processing pipelines used to derive brain phenotypes, as well as how quality control was assessed. In addition, we present preliminary results on associations of some of these brain image-derived phenotypes at the whole brain level with both age and sex, in the subsample of 1722 individuals aged less than 26 years. We demonstrate that the post-adolescence period is characterized by changes in both structural and microstructural brain phenotypes. Grey matter cortical thickness, surface area and volume were found to decrease with age, while white matter volume shows increase. Diffusivity, either radial or axial, was found to robustly decrease with age whereas fractional anisotropy only slightly increased. As for the neurite orientation dispersion and densities, both were found to increase with age. The isotropic volume fraction also showed a slight increase with age. These preliminary findings emphasize the complexity of changes in brain structure and function occurring in this critical period at the interface of late maturation and early ageing.

Cerebral small vessel disease genomics and its implications across the lifespan.

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

Development of handedness, anatomical and functional brain lateralization.

The present chapter offers a report on the recent literature on the neural bases of hemispheric specialization (HS), anatomical and functional developmental timecourse of HS, and on the available knowledge of their relationships with the development of handedness. Strong anatomical asymmetries can be seen located along the end of the sylvian fissure and the superior temporal sulcus (STS) as soon as the 23rd gestational week. They correspond to a leftward sulcal depth asymmetry of the Sylvian fissure coupled with a rightward asymmetry of STS. These neonatal asymmetries targeting speech processing areas do not further change with development. Different from these anatomical asymmetries, the functional asymmetries of language areas develop during childhood. Such a development is characterized at birth by a predominant interhemispheric intrinsic connectivity between homotopic areas that will evolve toward left hemisphere intrahemispheric intrinsic connectivity between anterior and posterior language poles. The development of such a typical architecture of language networks in the left hemisphere dominant for language in more than 90% of humans translates into a continuous increase in the leftward asymmetries of activation during language production throughout childhood. With regard to the rightward cerebral lateralization for visuospatial functions, neuroimaging studies tend to indicate an increase in rightward lateralization of frontal-parietal network with age during visuospatial memory and visuospatial search tasks. In addition, the spatial-attentional behavioral asymmetries emerge early (in preschool children) and, then, can be modulated by factors linked to motor asymmetry and handedness. Finally, the study of manual lateralization in relation to language development has shown the importance of considering several characteristics of manual activities. In particular, the dissociation between manipulative activities and communicative gestures in young children may open further perspectives for future research on HS.

Word Meaning Contributes to Free Recall Performance in Supraspan Verbal List-Learning Tests.

Supraspan verbal list-learning tests, such as the Rey Auditory Verbal Learning Test (RAVLT), are classic neuropsychological tests for assessing verbal memory. In this study, we investigated the impact of the meaning of the words to be learned on three memory stages [short-term recall (STR), learning, and delayed recall (DR)] in a cohort of 447 healthy adults. First, we compared scores obtained from the RAVLT (word condition) to those of an alternative version of this test using phonologically similar but meaningless items (pseudoword condition) and observed how each score varied as a function of age and sex. Then, we collected the participants' self-reported strategies to retain the word and pseudoword lists and examined if these strategies mediated the age and sex effects on memory scores. The word condition resulted in higher memory scores than pseudoword condition at each memory stage and even canceled out, for the learning stage, the detrimental effect of age that was observed for the short-term and DR. When taking sex into account, the word advantage was observed only in women for STR. The self-reported strategies, which were similar for words and pseudowords, were based on the position of the item on the list (word: 53%, pseudoword: 37%) or the meaning of the item (word: 64%, pseudoword: 58%) and were used alone or in combination. The best memory performance was associated with the meaning strategy in the word condition and with the combination of the meaning and position strategies in the pseudoword condition. Finally, we found that the word advantage observed in women for STR was mediated by the use of the meaning strategy. The RAVLT scores were thus highly dependent on word meaning, notably because it allowed efficient semantic knowledge-based strategies. Within the framework of Tulving's declarative memory model, these results are at odds with the depiction of the RAVLT as a verbal episodic memory test as it is increasingly referred to in the literature.

A population-based atlas of the human pyramidal tract in 410 healthy participants.

With the advances in diffusion MRI and tractography, numerous atlases of the human pyramidal tract (PyT) have been proposed, but the inherent limitation of tractography to resolve crossing bundles within the centrum semiovale has so far prevented the complete description of the most lateral PyT projections. Here, we combined a precise manual positioning of individual subcortical regions of interest along the descending pathway of the PyT with a new bundle-specific tractography algorithm. This later is based on anatomical priors to improve streamlines tracking in crossing areas. We then extracted both left and right PyT in a large cohort of 410 healthy participants and built a population-based atlas of the whole-fanning PyT with a complete description of its most corticolateral projections. Clinical applications are envisaged, the whole-fanning PyT atlas being likely a better marker of corticospinal integrity metrics than those currently used within the frame of prediction of poststroke motor recovery. The present population-based PyT, freely available, provides an interesting tool for clinical applications to locate specific PyT damage and its impact to the short- and long-term motor recovery after stroke.

What Are the Contributions of Handedness, Sighting Dominance, Hand Used to Bisect, and Visuospatial Line Processing to the Behavioral Line Bisection Bias?

In a sample of 60 French participants, we examined whether the variability in the behavioral deviation measured during the classical "paper and pencil" line bisection task was explained by individual laterality factors such as handedness and eye sighting dominance, as well as the hand used to bisect, and the spatial position of the line to bisect. The results showed the expected main effects of line position and hand used to bisect, as well as some interactions between factors. Specifically, the effect of the hand used to bisect on the deviation bias was different as a function of handedness and line position. In right-handers, there was a strong difference between the biases elicited by each hand, producing a hand-used asymmetry, observed for each spatial position of the line. In left-handers, there was no difference in deviation as a function of hand used to perform the bisection, except when all factors triggered attention toward the left side such as bisecting left-displaced lines, with the left dominant hand, producing a strong leftward deviation as compared to the reduced bias exhibited with the right non-dominant hand. Finally, the eye sighting dominance interacted with handedness and line position. Left-handers with a right sighting dominance showed a leftward bias when they bisected left-displaced lines, while right-handers with a left sighting dominance showed an inversed bias when they bisected rightward lines. Taken together, these findings suggest that the behavioral deviation bias relies on the integration of the hemispheric weights of the visuospatial processing of the stimuli, and the motoric component of the hand used to bisect, as well as those linked to individual laterality factors. When all these factors producing asymmetric cerebral activation coincide in the same direction, then their joint effect will provide the strongest asymmetric behavioral biases.

Predicting hemispheric dominance for language production in healthy individuals using support vector machine.

We used a Support Vector Machine (SVM) classifier to assess hemispheric pattern of language dominance of 47 individuals categorized as non-typical for language from their hemispheric functional laterality index (HFLI) measured on a sentence minus word-list production fMRI-BOLD contrast map. The SVM classifier was trained at discriminating between Dominant and Non-Dominant hemispheric language production activation pattern on a group of 250 participants previously identified as Typicals (HFLI strongly leftward). Then, SVM was applied to each hemispheric language activation pattern of 47 non-typical individuals. The results showed that at least one hemisphere (left or right) was found to be Dominant in every, except 3 individuals, indicating that the "dominant" type of functional organization is the most frequent in non-typicals. Specifically, left hemisphere dominance was predicted in all non-typical right-handers (RH) and in 57.4% of non-typical left-handers (LH). When both hemisphere classifications were jointly considered, four types of brain patterns were observed. The most often predicted pattern (51%) was left-dominant (Dominant left-hemisphere and Non-Dominant right-hemisphere), followed by right-dominant (23%, Dominant right-hemisphere and Non-Dominant left-hemisphere) and co-dominant (19%, 2 Dominant hemispheres) patterns. Co-non-dominant was rare (6%, 2 Non-Dominant hemispheres), but was normal variants of hemispheric specialization. In RH, only left-dominant (72%) and co-dominant patterns were detected, while for LH, all types were found, although with different occurrences. Among the 10 LH with a strong rightward HFLI, 8 had a right-dominant brain pattern. Whole-brain analysis of the right-dominant pattern group confirmed that it exhibited a functional organization strictly mirroring that of left-dominant pattern group. Hum Brain Mapp 38:5871-5889, 2017. © 2017 Wiley Periodicals, Inc.

Pseudoneglect in line bisection judgement is associated with a modulation of right hemispheric spatial attention dominance in right-handers.

The objective of this study was to validate a line bisection judgement (LBJ) task for use in investigating the lateralized cerebral bases of spatial attention in a sample of 51 right-handed healthy participants. Using functional magnetic resonance imaging (fMRI), the participants performed a LBJ task that was compared to a visuomotor control task during which the participants made similar saccadic and motoric responses. Cerebral lateralization was determined using a voxel-based functional asymmetry analysis and a hemispheric functional lateralization index (HFLI) computed from fMRI contrast images. Behavioural attentional deviation biases were assessed during the LBJ task and a "paper and pencil" symbol cancellation task (SCT). Individual visuospatial skills were also evaluated. The results showed that both the LBJ and SCT tasks elicited leftward spatial biases in healthy subjects, although the biases were not correlated, which indicated their independence. Neuroimaging results showed that the LBJ task elicited a right hemispheric lateralization, with rightward asymmetries found in a large posterior occipito-parietal area, the posterior calcarine sulcus (V1p) and the temporo-occipital junction (TOJ) and in the inferior frontal gyrus, the anterior insula and the superior medial frontal gyrus. The comparison of the LBJ asymmetry map to the lesion map of neglect patients who suffer line bisection deviation demonstrated maximum overlap in a network that included the middle occipital gyrus (MOG), the TOJ, the anterior insula and the inferior frontal region, likely subtending spatial LBJ bias. Finally, the LBJ task-related cerebral lateralization was specifically correlated with the LBJ spatial bias but not with the SCT bias or with the visuospatial skills of the participants. Taken together, these results demonstrated that the LBJ task is adequate for investigating spatial lateralization in healthy subjects and is suitable for determining the factors underlying the variability of spatial cerebral lateralization.

Revisiting the human uncinate fasciculus, its subcomponents and asymmetries with stem-based tractography and microdissection validation.

Despite its significant functional and clinical interest, the anatomy of the uncinate fasciculus (UF) has received little attention. It is known as a 'hook-shaped' fascicle connecting the frontal and anterior temporal lobes and is believed to consist of multiple subcomponents. However, the knowledge of its precise connectional anatomy in humans is lacking, and its subcomponent divisions are unclear. In the present study, we evaluate the anatomy of the UF and provide its detailed normative description in 30 healthy subjects with advanced particle-filtering tractography with anatomical priors and robustness to crossing fibers with constrained spherical deconvolution. We extracted the UF by defining its stem encompassing all streamlines that converge into a compact bundle, which consisted not only of the classic hook-shaped fibers, but also of straight horizontally oriented. We applied an automatic-clustering method to subdivide the UF bundle and revealed five subcomponents in each hemisphere with distinct connectivity profiles, including different asymmetries. A layer-by-layer microdissection of the ventral part of the external and extreme capsules using Klingler's preparation also demonstrated five types of uncinate fibers that, according to their pattern, depth, and cortical terminations, were consistent with the diffusion-based UF subcomponents. The present results shed new light on the UF cortical terminations and its multicomponent internal organization with extended cortical connections within the frontal and temporal cortices. The different lateralization patterns we report within the UF subcomponents reconcile the conflicting asymmetry findings of the literature. Such results clarifying the UF structural anatomy lay the groundwork for more targeted investigations of its functional role, especially in semantic language processing.

Cortical Terminations of the Inferior Fronto-Occipital and Uncinate Fasciculi: Anatomical Stem-Based Virtual Dissection.

We combined the neuroanatomists' approach of defining a fascicle as all fibers passing through its compact stem with diffusion-weighted tractography to investigate the cortical terminations of two association tracts, the inferior fronto-occipital fasciculus (IFOF) and the uncinate fasciculus (UF), which have recently been implicated in the ventral language circuitry. The aim was to provide a detailed and quantitative description of their terminations in 60 healthy subjects and to do so to apply an anatomical stem-based virtual dissection, mimicking classical post-mortem dissection, to extract with minimal a priori the IFOF and UF from tractography datasets. In both tracts, we consistently observed more extensive termination territories than their conventional definitions, within the middle and superior frontal, superior parietal and angular gyri for the IFOF and the middle frontal gyrus and superior, middle and inferior temporal gyri beyond the temporal pole for the UF. We revealed new insights regarding the internal organization of these tracts by investigating for the first time the frequency, distribution and hemispheric asymmetry of their terminations. Interestingly, we observed a dissociation between the lateral right-lateralized and medial left-lateralized fronto-occipital branches of the IFOF. In the UF, we observed a rightward lateralization of the orbito-frontal and temporal branches. We revealed a more detailed map of the terminations of these fiber pathways that will enable greater specificity for correlating with diseased populations and other behavioral measures. The limitations of the diffusion tensor model in this study are also discussed. We conclude that anatomical stem-based virtual dissection with diffusion tractography is a fruitful method for studying the structural anatomy of the human white matter pathways.

What Is the Role of Manual Preference in Hand-Digit Mapping During Finger Counting? A Study in a Large Sample of Right- and Left-Handers.

The goal of the present study was to test whether there is a relationship between manual preference and hand-digit mapping in 369 French adults with similar numbers of right- and left-handers. Manual laterality was evaluated with the finger tapping test to evaluate hand motor asymmetry, and the Edinburgh handedness inventory was used to assess manual preference strength (MPS) and direction. Participants were asked to spontaneously "count on their fingers from 1 to 10" without indications concerning the hand(s) to be used. The results indicated that both MPS and hand motor asymmetry affect the hand-starting preference for counting. Left-handers with a strong left-hand preference (sLH) or left-hand motor asymmetry largely started to count with their left hand (left-starter), while right-handers with a strong right-hand preference (sRH) or right-hand motor asymmetry largely started to count with their right hand (right-starter). Notably, individuals with weak MPS did not show a hand-starting preference. These findings demonstrated that manual laterality contributes to finger counting directionality. Lastly, the results showed a higher proportion of sLH left-starter individuals compared with sRH right-starters, indicating an asymmetric bias of MPS on hand-starting preference. We hypothesize that the higher proportion of sLH left-starters could be explained by the congruence between left-to-right hand-digit mapping and left-to-right mental number line representation that has been largely reported in the literature. Taken together, these results indicate that finger-counting habits integrate biological and cultural information.

The association between hemispheric specialization for language production and for spatial attention depends on left-hand preference strength.

Cerebral lateralization for language production and spatial attention and their relationships with manual preference strength (MPS) were assessed in a sample of 293 healthy volunteers, including 151 left-handers, using fMRI during covert sentence production (PROD) and line bisection judgment (LBJ) tasks, as compared to high- and low-level reference tasks. At the group level, we found the expected complementary hemispheric specialization (HS) with leftward asymmetries for PROD within frontal and temporal regions and rightward asymmetries for LBJ within frontal and posterior occipito-parieto-temporal regions. Individual hemispheric (HLI) and regional (frontal and occipital) lateralization indices (LI) were then calculated on the activation maps for PROD and LBJ. We found a correlation between the degree of rightward cerebral asymmetry and the leftward behavioral attentional bias recorded during LBJ task. This correlation was found when LBJ-LI was computed over the hemispheres, in the frontal lobes, but not in the occipital lobes. We then investigated whether language production and spatial attention cerebral lateralization relate to each other, and whether manual preference was a variable that impacted the complementary HS of these functions. No correlation was found between spatial and language LIs in the majority of our sample of participants, including right-handers with a strong right-hand preference (sRH, n=97) and mixed-handers (MH, n=97), indicating that these functions lateralized independently. By contrast, in the group of left-handers with a strong left-hand preference (sLH, n= 99), a negative correlation was found between language and spatial lateralization. This negative correlation was found when LBJ-LI and PROD-LI were computed over the hemispheres, in the frontal lobes and between the occipital lobes for LBJ and the frontal lobes for PROD. These findings underline the importance to include sLH in the study sample to reveal the underlying mechanisms of complementary HS.

AICHA: An atlas of intrinsic connectivity of homotopic areas.

BACKGROUND: Atlases of brain anatomical ROIs are widely used for functional MRI data analysis. Recently, it was proposed that an atlas of ROIs derived from a functional brain parcellation could be advantageous, in particular for understanding how different regions share information. However, functional atlases so far proposed do not account for a crucial aspect of cerebral organization, namely homotopy, i.e. that each region in one hemisphere has a homologue in the other hemisphere. NEW METHOD: We present AICHA (for Atlas of Intrinsic Connectivity of Homotopic Areas), a functional brain ROIs atlas based on resting-state fMRI data acquired in 281 individuals. AICHA ROIs cover the whole cerebrum, each having 1-homogeneity of its constituting voxels intrinsic activity, and 2-a unique homotopic contralateral counterpart with which it has maximal intrinsic connectivity. AICHA was built in 4 steps: (1) estimation of resting-state networks (RSNs) using individual resting-state fMRI independent components, (2) k-means clustering of voxel-wise group level profiles of connectivity, (3) homotopic regional grouping based on maximal inter-hemispheric functional correlation, and (4) ROI labeling. RESULTS: AICHA includes 192 homotopic region pairs (122 gyral, 50 sulcal, and 20 gray nuclei). As an application, we report inter-hemispheric (homotopic and heterotopic) and intra-hemispheric connectivity patterns at different sparsities. COMPARISON WITH EXISTING METHOD: ROI functional homogeneity was higher for AICHA than for anatomical ROI atlases, but slightly lower than for another functional ROI atlas not accounting for homotopy. CONCLUSION: AICHA is ideally suited for intrinsic/effective connectivity analyses, as well as for investigating brain hemispheric specialization.

Strong rightward lateralization of the dorsal attentional network in left-handers with right sighting-eye: an evolutionary advantage.

Hemispheric lateralization for spatial attention and its relationships with manual preference strength and eye preference were studied in a sample of 293 healthy individuals balanced for manual preference. Functional magnetic resonance imaging was used to map this large sample while performing visually guided saccadic eye movements. This activated a bilateral distributed cortico-subcortical network in which dorsal and ventral attentional/saccadic pathways elicited rightward asymmetrical activation depending on manual preference strength and sighting eye. While the ventral pathway showed a strong rightward asymmetry irrespective of both manual preference strength and eye preference, the dorsal frontoparietal network showed a robust rightward asymmetry in strongly left-handers, even more pronounced in left-handed subjects with a right sighting-eye. Our findings brings support to the hypothesis that the origin of the rightward hemispheric dominance for spatial attention may have a manipulo-spatial origin neither perceptual nor motor per se but rather reflecting a mechanism by which a spatial context is mapped onto the perceptual and motor activities, including the exploration of the spatial environment with eyes and hands. Within this context, strongly left-handers with a right sighting-eye may benefit from the advantage of having the same right hemispheric control of their dominant hand and visuospatial attention processing. We suggest that this phenomenon explains why left-handed right sighting-eye athletes can outperform their competitors in sporting duels and that the prehistoric and historical constancy of the left-handers ratio over the general population may relate in part on the hemispheric specialization of spatial attention.

Gaussian mixture modeling of hemispheric lateralization for language in a large sample of healthy individuals balanced for handedness.

Hemispheric lateralization for language production and its relationships with manual preference and manual preference strength were studied in a sample of 297 subjects, including 153 left-handers (LH). A hemispheric functional lateralization index (HFLI) for language was derived from fMRI acquired during a covert sentence generation task as compared with a covert word list recitation. The multimodal HFLI distribution was optimally modeled using a mixture of 3 and 4 Gaussian functions in right-handers (RH) and LH, respectively. Gaussian function parameters helped to define 3 types of language hemispheric lateralization, namely "Typical" (left hemisphere dominance with clear positive HFLI values, 88% of RH, 78% of LH), "Ambilateral" (no dominant hemisphere with HFLI values close to 0, 12% of RH, 15% of LH) and "Strongly-atypical" (right-hemisphere dominance with clear negative HFLI values, 7% of LH). Concordance between dominant hemispheres for hand and for language did not exceed chance level, and most of the association between handedness and language lateralization was explained by the fact that all Strongly-atypical individuals were left-handed. Similarly, most of the relationship between language lateralization and manual preference strength was explained by the fact that Strongly-atypical individuals exhibited a strong preference for their left hand. These results indicate that concordance of hemispheric dominance for hand and for language occurs barely above the chance level, except in a group of rare individuals (less than 1% in the general population) who exhibit strong right hemisphere dominance for both language and their preferred hand. They call for a revisit of models hypothesizing common determinants for handedness and for language dominance.

Revisiting human hemispheric specialization with neuroimaging.

Hemispheric specialization (HS) is a hemisphere-dependent relationship between a cognitive, sensory, or motor function and a set of brain structures. It includes both the hosting by a given hemisphere of specialized networks that have unique functional properties and mechanisms that enable the inter-hemispheric coordination necessary for efficient processing. Long derived from neuropsychological and behavioral observations, knowledge of HS is currently being profoundly modified by cutting-edge neuroimaging research that focuses both on the neural implementation of HS for language, visuospatial functions, and motor control/handedness across development and on the analysis of interactions between brain regions within and across hemispheres. New findings reveal the fundamental role of lateralization in the large-scale architecture of the human brain, whose ontogenesis has begun to be investigated with genetic-heritability brain mapping.

A novel group ICA approach based on multi-scale individual component clustering. Application to a large sample of fMRI data.

Functional connectivity-based analysis of functional magnetic resonance imaging data (fMRI) is an emerging technique for human brain mapping. One powerful method for the investigation of functional connectivity is independent component analysis (ICA) of concatenated data. However, this research field is evolving toward processing increasingly larger database taking into account inter-individual variability. Concatenated data analysis only handles these features using some additional procedures such as bootstrap or including a model of between-subject variability during the preprocessing step of the ICA. In order to alleviate these limitations, we propose a method based on group analysis of individual ICA components, using a multi-scale clustering (MICCA). MICCA start with two steps repeated several times: 1) single subject data ICA followed by 2) clustering of all subject independent components according to a spatial similarity criterion. A final third step consists in selecting reproducible clusters across the repetitions of the two previous steps. The core of the innovation lies in the multi-scale and unsupervised clustering algorithm built as a chain of three processes: robust proto-cluster creation, aggregation of the proto-clusters, and cluster consolidation. We applied MICCA to the analysis of 310 fMRI resting state dataset. MICCA identified 28 resting state brain networks. Overall, the cluster neuroanatomical substrate included 98% of the cerebrum gray matter. MICCA results proved to be reproducible in a random splitting of the data sample and more robust than the classical concatenation method.