Rationale and design of the PACIFIC-PRESERVED (PhenomApping, ClassIFication and Innovation for Cardiac dysfunction in patients with heart failure and PRESERVED left ventricular ejection fraction) study.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that is poorly defined, reflecting an incomplete understanding of its pathophysiology. AIM: To redefine the phenotypic spectrum of HFpEF. METHODS: The PACIFIC-PRESERVED study is a prospective multicentre cohort study designed to perform multidimensional deep phenotyping of patients diagnosed with HFpEF (left ventricular ejection fraction≥50%), patients with heart failure with reduced ejection fraction (left ventricular ejection fraction≤40%) and subjects without overt heart failure (3:2:1 ratio). The study proposes prospective investigations in patients during a 1-day hospital stay: physical examination; electrocardiogram; performance-based tests; blood samples; cardiac magnetic resonance imaging; transthoracic echocardiography (rest and low-level exercise); myocardial shear wave elastography; chest computed tomography; and non-invasive measurement of arterial stiffness. Dyspnoea, depression, general health and quality of life will be assessed by dedicated questionnaires. A biobank will be established. After the hospital stay, patients are asked to wear a connected garment (with digital sensors) to collect electrocardiography, pulmonary and activity variables in real-life conditions (for up to 14 days). Data will be centralized for machine-learning-based analyses, with the aim of reclassifying HFpEF into more distinct subgroups, improving understanding of the disease mechanisms and identifying new biological pathways and molecular targets. The study will also serve as a platform to enable the development of innovative technologies and strategies for the diagnosis and stratification of patients with HFpEF. CONCLUSIONS: PACIFIC-PRESERVED is a prospective multicentre phenomapping study, using novel analytical techniques, which will provide a unique data resource to better define HFpEF and identify new clinically meaningful subgroups of patients.

The PACIFIC ontology for heterogeneous data management in cardiology.

With the emergence of health data warehouses and major initiatives to collect and analyze multi-modal and multisource data, data organization becomes central. In the PACIFIC-PRESERVED (PhenomApping, ClassIFication, and Innovation for Cardiac Dysfunction - Heart Failure with PRESERVED LVEF Study, NCT04189029) study, a data driven research project aiming at redefining and profiling the Heart Failure with preserved Ejection Fraction (HFpEF), an ontology was developed by different data experts in cardiology to enable better data management in a complex study context (multisource, multiformat, multimodality, multipartners). The PACIFIC ontology provides a cardiac data management framework for the phenomapping of patients. It was built upon the BMS-LM (Biomedical Study -Lifecycle Management) core ontology and framework, proposed in a previous work to ensure data organization and provenance throughout the study lifecycle (specification, acquisition, analysis, publication). The BMS-LM design pattern was applied to the PACIFIC multisource variables. In addition, data was structured using a subset of MeSH headings for diseases, technical procedures, or biological processes, and using the Uberon ontology anatomical entities. A total of 1372 variables were organized and enriched with annotations and description from existing ontologies and taxonomies such as LOINC to enable later semantic interoperability. Both, data structuring using the BMS-LM framework, and its mapping with published standards, foster interoperability of multimodal cardiac phenomapping datasets.

The BMS-LM ontology for biomedical data reporting throughout the lifecycle of a research study: From data model to ontology.

Biomedical research data reuse and sharing is essential for fostering research progress. To this aim, data producers need to master data management and reporting through standard and rich metadata, as encouraged by open data initiatives such as the FAIR (Findable, Accessible, Interoperable, Reusable) guidelines. This helps data re-users to understand and reuse the shared data with confidence. Therefore, dedicated frameworks are required. The provenance reporting throughout a biomedical study lifecycle has been proposed as a way to increase confidence in data while reusing it. The Biomedical Study - Lifecycle Management (BMS-LM) data model has implemented provenance and lifecycle traceability for several multimodal-imaging techniques but this is not enough for data understanding while reusing it. Actually, in the large scope of biomedical research, a multitude of metadata sources, also called Knowledge Organization Systems (KOSs), are available for data annotation. In addition, data producers uses local terminologies or KOSs, containing vernacular terms for data reporting. The result is a set of heterogeneous KOSs (local and published) with different formats and levels of granularity. To manage the inherent heterogeneity, semantic interoperability is encouraged by the Research Data Management (RDM) community. Ontologies, and more specifically top ontologies such as BFO and DOLCE, make explicit the metadata semantics and enhance semantic interoperability. Based on the BMS-LM data model and the BFO top ontology, the BioMedical Study - Lifecycle Management (BMS-LM) core ontology is proposed together with an associated framework for semantic interoperability between heterogeneous KOSs. It is made of four ontological levels: top/core/domain/local and aims to build bridges between local and published KOSs. In this paper, the conversion of the BMS-LM data model to a core ontology is detailed. The implementation of its semantic interoperability in a specific domain context is explained and illustrated with examples from small animal preclinical research.

Deep Learning-based Classification of Resting-state fMRI Independent-component Analysis.

Functional connectivity analyses of fMRI data have shown that the activity of the brain at rest is spatially organized into resting-state networks (RSNs). RSNs appear as groups of anatomically distant but functionally tightly connected brain regions. Inter-RSN intrinsic connectivity analyses may provide an optimal spatial level of integration to analyze the variability of the functional connectome. Here we propose a deep learning approach to enable the automated classification of individual independent-component (IC) decompositions into a set of predefined RSNs. Two databases were used in this work, BIL&GIN and MRi-Share, with 427 and 1811 participants, respectively. We trained a multilayer perceptron (MLP) to classify each IC as one of 45 RSNs, using the IC classification of 282 participants in BIL&GIN for training and a 5-dimensional parameter grid search for hyperparameter optimization. It reached an accuracy of 92 %. Predictions for the remaining individuals in BIL&GIN were tested against the original classification and demonstrated good spatial overlap between the cortical RSNs. As a first application, we created an RSN atlas based on MRi-Share. This atlas defined a brain parcellation in 29 RSNs covering 96 % of the gray matter. Second, we proposed an individual-based analysis of the subdivision of the default-mode network into 4 networks. Minimal overlap between RSNs was found except in the angular gyrus and potentially in the precuneus. We thus provide the community with an individual IC classifier that can be used to analyze one dataset or to statistically compare different datasets for RSN spatial definitions.

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.

Functional deficit of the medial prefrontal cortex during emotional sentence attribution in schizophrenia.

BACKGROUND: Functional brain imaging research has already demonstrated that patients with schizophrenia had difficulties with emotion processing, namely in facial emotion perception and emotional prosody. However, the moderating effect of social context and the boundary of perceptual categories of emotion attribution remain unclear. This study investigated the neural bases of emotional sentence attribution in schizophrenia. METHODS: Twenty-one schizophrenia patients and 25 healthy subjects underwent an event-related functional magnetic resonance imaging paradigm including two tasks: one to classify sentences according to their emotional content, and the other to classify neutral sentences according to their grammatical person. RESULTS: First, patients showed longer response times as compared to controls only during the emotion attribution task. Second, patients with schizophrenia showed reduction of activation in bilateral auditory areas irrespective of the presence of emotions. Lastly, during emotional sentences attribution, patients displayed less activation than controls in the medial prefrontal cortex (mPFC). CONCLUSIONS: We suggest that the functional abnormality observed in the mPFC during the emotion attribution task could provide a biological basis for social cognition deficits in patients with schizophrenia.

A shared neural substrate for mentalizing and the affective component of sentence comprehension.

Using event-related fMRI in a sample of 42 healthy participants, we compared the cerebral activity maps obtained when classifying spoken sentences based on the mental content of the main character (belief, deception or empathy) or on the emotional tonality of the sentence (happiness, anger or sadness). To control for the effects of different syntactic constructions (such as embedded clauses in belief sentences), we subtracted from each map the BOLD activations obtained during plausibility judgments on structurally matching sentences, devoid of emotions or ToM. The obtained theory of mind (ToM) and emotional speech comprehension networks overlapped in the bilateral temporo-parietal junction, posterior cingulate cortex, right anterior temporal lobe, dorsomedial prefrontal cortex and in the left inferior frontal sulcus. These regions form a ToM network, which contributes to the emotional component of spoken sentence comprehension. Compared with the ToM task, in which the sentences were enounced on a neutral tone, the emotional sentence classification task, in which the sentences were play-acted, was associated with a greater activity in the bilateral superior temporal sulcus, in line with the presence of emotional prosody. Besides, the ventromedial prefrontal cortex was more active during emotional than ToM sentence processing. This region may link mental state representations with verbal and prosodic emotional cues. Compared with emotional sentence classification, ToM was associated with greater activity in the caudate nucleus, paracingulate cortex, and superior frontal and parietal regions, in line with behavioral data showing that ToM sentence comprehension was a more demanding task.

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.

Disentangling the brain networks supporting affective speech comprehension.

Areas involved in social cognition, such as the medial prefrontal cortex (mPFC) and the left temporo-parietal junction (TPJ) appear to be active during the classification of sentences according to emotional criteria (happy, angry or sad, [Beaucousin et al., 2007]). These two regions are frequently co-activated in studies about theory of mind (ToM). To confirm that these regions constitute a coherent network during affective speech comprehension, new event-related functional magnetic resonance imaging data were acquired, using the emotional and grammatical-person sentence classification tasks on a larger sample of 51 participants. The comparison of the emotional and grammatical tasks confirmed the previous findings. Functional connectivity analyses established a clear demarcation between a "Medial" network, including the mPFC and TPJ regions, and a bilateral "Language" network, which gathered inferior frontal and temporal areas. These findings suggest that emotional speech comprehension results from interactions between language, ToM and emotion processing networks. The language network, active during both tasks, would be involved in the extraction of lexical and prosodic emotional cues, while the medial network, active only during the emotional task, would drive the making of inferences about the sentences' emotional content, based on their meanings. The left and right amygdalae displayed a stronger response during the emotional condition, but were seldom correlated with the other regions, and thus formed a third entity. Finally, distinct regions belonging to the Language and Medial networks were found in the left angular gyrus, where these two systems could interface.

Anatomical correlates of dynamic auditory processing: relationship to literacy during early adolescence.

Adults show great variation in their auditory skills, such as being able to discriminate between foreign speech-sounds. Previous research has demonstrated that structural features of auditory cortex can predict auditory abilities; here we are interested in the maturation of 2-Hz frequency-modulation (FM) detection, a task thought to tap into mechanisms underlying language abilities. We hypothesized that an individual's FM threshold will correlate with gray-matter density in left Heschl's gyrus, and that this function-structure relationship will change through adolescence. To test this hypothesis, we collected anatomical magnetic resonance imaging data from participants who were tested and scanned at three time points: at 10, 11.5 and 13 years of age. Participants judged which of two tones contained FM; the modulation depth was adjusted using an adaptive staircase procedure and their threshold was calculated based on the geometric mean of the last eight reversals. Using voxel-based morphometry, we found that FM threshold was significantly correlated with gray-matter density in left Heschl's gyrus at the age of 10 years, but that this correlation weakened with age. While there were no differences between girls and boys at Times 1 and 2, at Time 3 there was a relationship between gray-matter density in left Heschl's gyrus in boys but not in girls. Taken together, our results confirm that the structure of the auditory cortex can predict temporal processing abilities, namely that gray-matter density in left Heschl's gyrus can predict 2-Hz FM detection threshold. This ability is dependent on the processing of sounds changing over time, a skill believed necessary for speech processing. We tested this assumption and found that FM threshold significantly correlated with spelling abilities at Time 1, but that this correlation was found only in boys. This correlation decreased at Time 2, and at Time 3 we found a significant correlation between reading and FM threshold, but again, only in boys. We examined the sex differences in both the imaging and behavioral data taking into account pubertal stages, and found that the correlation between FM threshold and spelling was strongest pre-pubertally, and the correlation between FM threshold and gray-matter density in left Heschl's gyrus was strongest mid-pubertally.

Structural properties of the corticospinal tract in the human brain: a magnetic resonance imaging study at 7 Tesla.

Several fibre tracts can be accurately located using conventional Magnetic Resonance Images (MRI) of the human brain, including the corticospinal tract (CST), which appears as a T (1)-weighted hypointense/T (2)-weighted hyperintense patch in the posterior part of the posterior-limb of the internal capsule (PLIC). Here we use high-field MRI (7T) to assess the quantitative MRI properties of the CST at the PLIC level in 22 healthy young male participants. We used three different imaging modalities: the T (1) and T (2) relaxation times (T (1) and T (2)) and the Magnetization Transfer Ratio (MTR). These measurements obtained in the CST were compared with those in the anterior two-thirds of the PLIC. We observed longer T (1) and T (2) and lower MTR in the CST region compared with the adjacent (control) PLIC region. This effect is consistent with the presence of sparsely distributed, large-diameter fibres described in previous histological studies and, as such, might reflect lower myelin density and/or different morphology of fibres in the CST.

Sex-dependent modulation of activity in the neural networks engaged during emotional speech comprehension.

Studies using event related potentials have shown that men are more likely than women to rely on semantic cues when understanding emotional speech. In a previous functional Magnetic Resonance Imaging (fMRI) study, using an affective sentence classification task, we were able to separate areas involved in semantic processing and areas involved in the processing of affective prosody (Beaucousin et al., 2007). Here we searched for sex-related differences in the neural networks active during emotional speech processing in groups of men and women. The ortholinguistic abilities of the participants did not differ when evaluated with a large battery of tests. Although the neural networks engaged by men and women during emotional sentence classification were largely overlapping, sex-dependent modulations were detected during emotional sentence classification, but not during grammatical sentence classification. Greater activity was observed in men, compared with women, in inferior frontal cortical areas involved in emotional labeling and in attentional areas. In conclusion, at equivalent linguistic abilities and performances, men activate semantic and attentional cortical areas to a larger extent than women during emotional speech processing.

Reproducibility of fMRI activations during a story listening task in patients with schizophrenia.

A prerequisite to longitudinal fMRI studies in schizophrenia is the knowledge on fMRI signal reliability in schizophrenia patients. We assessed the reproducibility of activations elicited by two fMRI sessions, which were 21 months apart, of a story listening paradigm in 10 schizophrenia patients and 10 healthy subjects. In both groups, we observed a high degree of spatial overlap of activation maps as well as a good reproducibility of signal variations assessed on a voxel-wise basis in temporal areas underlying early stages of language processing. Task performance, assessed through a comprehension questionnaire, had no impact on the activation reproducibility.

A common neural system is activated in hearing non-signers to process French sign language and spoken French.

We used functional magnetic resonance imaging to investigate the areas activated by signed narratives in non-signing subjects naïve to sign language (SL) and compared it to the activation obtained when hearing speech in their mother tongue. A subset of left hemisphere (LH) language areas activated when participants watched an audio-visual narrative in their mother tongue was activated when they observed a signed narrative. The inferior frontal (IFG) and precentral (Prec) gyri, the posterior parts of the planum temporale (pPT) and of the superior temporal sulcus (pSTS), and the occipito-temporal junction (OTJ) were activated by both languages. The activity of these regions was not related to the presence of communicative intent because no such changes were observed when the non-signers watched a muted video of a spoken narrative. Recruitment was also not triggered by the linguistic structure of SL, because the areas, except pPT, were not activated when subjects listened to an unknown spoken language. The comparison of brain reactivity for spoken and sign languages shows that SL has a special status in the brain compared to speech; in contrast to unknown oral language, the neural correlates of SL overlap LH speech comprehension areas in non-signers. These results support the idea that strong relationships exist between areas involved in human action observation and language, suggesting that the observation of hand gestures have shaped the lexico-semantic language areas as proposed by the motor theory of speech. As a whole, the present results support the theory of a gestural origin of language.

What is right-hemisphere contribution to phonological, lexico-semantic, and sentence processing? Insights from a meta-analysis.

To evaluate the relative role of left and right hemispheres (RH) and describe the functional anatomy of RH during ortholinguistic tasks, we re-analyzed the 128 papers of a former left-hemisphere (LH) meta-analysis (Vigneau et al., 2006). Of these, 59 articles reported RH participation, providing 105 RH language contrasts including 218 peaks compared to 728 on the left, a proportion reflecting the LH language dominance. To describe inter-hemispheric interactions, in each of the language contrasts involving both hemispheres, we distinguished between unilateral and bilateral peaks, i.e. having homotopic activation in the LH in the same contrast. We also calculated the proportion of bilateral peaks in the LH. While the majority of LH peaks were unilateral (79%), a reversed pattern was observed in the RH; this demonstrates that, in contrast to the LH, the RH works in an inter-hemispheric manner. To analyze the regional pattern of RH participation, these unilateral and bilateral peaks were spatially clustered for each language component. Most RH phonological clusters corresponded to bilateral recruitment of auditory and motor cortices. Notably, the motor representation of the mouth and phonological working memory areas were exclusively left-lateralized, supporting the idea that the RH does not host phonological representations. Right frontal participation was not specific for the language component involved and appeared related to the recruitment of attentional and working memory areas. The fact that RH participation during lexico-semantic tasks was limited to these executive activations is compatible with the hypothesis that active inhibition is exerted from the LH during the processing of meaning. Only during sentence/text processing tasks a specific unilateral RH-temporal involvement was noted, likely related to context processing. These results are consistent with split-brain studies that found that the RH has a limited lexicon, with no phonological abilities but active involvement in the processing of context.

Impact of cognitive performance on the reproducibility of fMRI activation in schizophrenia.

BACKGROUND: Longitudinal functional magnetic resonance imaging (fMRI) studies in patients with schizophrenia allow exploration of the course of the illness and brain activity after therapy. A crucial question, however, is whether fMRI findings are reliable, because they can be affected by performance deficits in patients with schizophrenia. Our aim was to evaluate the reproducibility of fMRI activations in highly integrated language areas in patients with schizophrenia, taking into account task performance. METHODS: Ten patients with schizophrenia and 10 matched healthy controls were scanned twice, 21 months apart, while performing a story comprehension task. The reproducibility of the activations in each participant was evaluated globally by the percentage of spatial overlap between the 2 sessions and locally by a voxel-wise computation of the between-session relative standard deviation. We performed between-group comparisons both with and without the inclusion of comprehension scores (measuring task performance) as a covariate. RESULTS: On average, patients with schizophrenia had significantly lower comprehension scores than controls (4.5/12 v. 7.8/12, p = 0.002). The mean spatial overlap between fMRI sessions was 30.6% in the patient group and 47.0% in the control group (p = 0.017). Locally, the lower reproducibility in patients was most prominent in the left posterior middle temporal gyrus, inferior frontal gyrus and medial prefrontal cortex (p < 0.001 uncorrected for multiple comparisons). Comprehension scores were positively correlated with both reproducibility measures in patients (overlap: r = 0.82, p = 0.004; relative standard deviation: several significant clusters at p < 0.001). When we included the comprehension scores as a covariate, most of the local between-group differences in reproducibility were removed, and the difference in overlap was not significant. LIMITATIONS: Owing to the small sample size, we could not investigate the impact of clinical subtypes and different types of medications on reproducibility. CONCLUSION: Our findings suggest that the greater variability in activation in patients with schizophrenia compared with controls concerns high-level areas and is mainly attributable to deficient task performance. Consequently, cognitive performance must be carefully controlled when longitudinal fMRI studies are undertaken.

Effect of familial sinistrality on planum temporale surface and brain tissue asymmetries.

The impact of having left-handers (LHs) among one's close relatives, called familial sinistrality (FS), on neuroanatomical markers of left-hemisphere language specialization was studied in 274 normal adults, including 199 men and 75 women, among whom 77 men and 27 women were positive for FS. Measurements of the surface of a phonological cortical area, the "planum temporale" (PT), and gray and white matter hemispheric volumes and asymmetries were made using brain magnetic resonance images. The size of the left PT of subjects with left-handed close relatives (FS+) was reduced by 10%, decreasing with the number of left-handed relatives, and lowest when the subject's mother was left-handed. Such findings had no counterparts in the right hemisphere, and the subject's handedness and sex were found to have no significant effect or interaction with FS on the left PT size. The FS+ subjects also exhibited increased gray matter volume, reduced hemispheric gray matter leftward asymmetry, and, in LHs, reduced strength of hand preference. These results add to the increasing body of evidence suggesting multiple and somewhat independent mechanisms for the inheritance of hand and language lateralization.

Handedness, motor skills and maturation of the corticospinal tract in the adolescent brain.

With anatomical magnetic resonance imaging, the signal intensity of the corticospinal tract (CST) at the level of the internal capsule is often paradoxically similar to that of grey matter. As shown previously in histological studies, this is likely due to the presence of very large axons. We measured the apparent grey-matter density (aGMd) of the putative CST (pCST) in a large cohort of adolescents (n = 409, aged 12-18 years). We tested the following hypotheses: (1) The aGMd in the pCST shows a hemispheric asymmetry that is, in turn, related to hand preference; (2) the maturation of the CST during adolescence differs between both sexes, due to the influence of testosterone; (3) variations in aGMd in the pCST reflect inter-individual differences in manual skills. We confirmed the first two predictions. Thus, we found a strong left > right hemispheric asymmetry in aGMd that was, on average, less marked in the 40 left-handed subjects. Apparent GMd in the pCST increased with age in adolescent males but not females, and this was particularly related to rising plasma levels of testosterone in male adolescents. This finding is compatible with the idea that testosterone influences axonal calibre rather than myelination. The third prediction, namely that of a relationship between age-related changes in manual skills and maturation of the pCST, was not confirmed. We conclude that the leftward asymmetry of the pCST may reflect an early established asymmetry in the number of large corticomotoneuronal fibres in the pCST.

Parcellation of fMRI datasets with ICA and PLS--a data driven approach.

Inter-subject parcellation of functional Magnetic Resonance Imaging (fMRI) data based on a standard General Linear Model (GLM) and spectral clustering was recently proposed as a means to alleviate the issues associated with spatial normalization in fMRI. However, for all its appeal, a GLM-based parcellation approach introduces its own biases, in the form of a priori knowledge about the shape of Hemodynamic Response Function (HRF) and task-related signal changes, or about the subject behaviour during the task. In this paper, we introduce a data-driven version of the spectral clustering parcellation, based on Independent Component Analysis (ICA) and Partial Least Squares (PLS) instead of the GLM. First, a number of independent components are automatically selected. Seed voxels are then obtained from the associated ICA maps and we compute the PLS latent variables between the fMRI signal of the seed voxels (which covers regional variations of the HRF) and the principal components of the signal across all voxels. Finally, we parcellate all subjects data with a spectral clustering of the PLS latent variables. We present results of the application of the proposed method on both single-subject and multi-subject fMRI datasets. Preliminary experimental results, evaluated with intra-parcel variance of GLM t-values and PLS derived t-values, indicate that this data-driven approach offers improvement in terms of parcellation accuracy over GLM based techniques.

Growth of white matter in the adolescent brain: role of testosterone and androgen receptor.

The growth of white matter during human adolescence shows a striking sexual dimorphism; the volume of white matter increases with age slightly in girls and steeply in boys. Here, we provide evidence supporting the role of androgen receptor (AR) in mediating the effect of testosterone on white matter. In a large sample of typically developing adolescents (n = 408, 204 males), we used magnetic resonance imaging and acquired T1-weighted and magnetization transfer ratio (MTR) images. We also measured plasma levels of testosterone and genotyped a functional polymorphism in the AR gene, namely the number of CAG repeats in exon 1 believed to be inversely proportional to the AR transcriptional activity. We found that the testosterone-related increase of white-matter volume was stronger in male adolescents with the lower versus higher number of CAG repeats in the AR gene, with testosterone explaining, respectively, 26 and 8% of variance in the volume. The MTR results suggest that this growth is not related to myelination; the MTR decreased with age in male adolescents. We speculate that testosterone affects axonal caliber rather than the thickness of the myelin sheath.