Short fiber bundle filtering and test-retest reproducibility of the Superficial White Matter.

In recent years, there has been a growing interest in studying the Superficial White Matter (SWM). The SWM consists of short association fibers connecting near giry of the cortex, with a complex organization due to their close relationship with the cortical folding patterns. Therefore, their segmentation from dMRI tractography datasets requires dedicated methodologies to identify the main fiber bundle shape and deal with spurious fibers. This paper presents an enhanced short fiber bundle segmentation based on a SWM bundle atlas and the filtering of noisy fibers. The method was tuned and evaluated over HCP test-retest probabilistic tractography datasets (44 subjects). We propose four fiber bundle filters to remove spurious fibers. Furthermore, we include the identification of the main fiber fascicle to obtain well-defined fiber bundles. First, we identified four main bundle shapes in the SWM atlas, and performed a filter tuning in a subset of 28 subjects. The filter based on the Convex Hull provided the highest similarity between corresponding test-retest fiber bundles. Subsequently, we applied the best filter in the 16 remaining subjects for all atlas bundles, showing that filtered fiber bundles significantly improve test-retest reproducibility indices when removing between ten and twenty percent of the fibers. Additionally, we applied the bundle segmentation with and without filtering to the ABIDE-II database. The fiber bundle filtering allowed us to obtain a higher number of bundles with significant differences in fractional anisotropy, mean diffusivity, and radial diffusivity of Autism Spectrum Disorder patients relative to controls.

A brief tablet-based intervention benefits linguistic and communicative abilities in toddlers and preschoolers.

Young children's linguistic and communicative abilities are foundational for their academic achievement and overall well-being. We present the positive outcomes of a brief tablet-based intervention aimed at teaching toddlers and preschoolers new word-object and letter-sound associations. We conducted two experiments, one involving toddlers ( ~ 24 months old, n = 101) and the other with preschoolers ( ~ 42 months old, n = 152). Using a pre-post equivalent group design, we measured the children's improvements in language and communication skills resulting from the intervention. Our results showed that the intervention benefited toddlers' verbal communication and preschoolers' speech comprehension. Additionally, it encouraged vocalizations in preschoolers and enhanced long-term memory for the associations taught in the study for all participants. In summary, our study demonstrates that the use of a ludic tablet-based intervention for teaching new vocabulary and pre-reading skills can improve young children's linguistic and communicative abilities, which are essential for future development.

Phybers: a package for brain tractography analysis.

We present a Python library (Phybers) for analyzing brain tractography data. Tractography datasets contain streamlines (also called fibers) composed of 3D points representing the main white matter pathways. Several algorithms have been proposed to analyze this data, including clustering, segmentation, and visualization methods. The manipulation of tractography data is not straightforward due to the geometrical complexity of the streamlines, the file format, and the size of the datasets, which may contain millions of fibers. Hence, we collected and structured state-of-the-art methods for the analysis of tractography and packed them into a Python library, to integrate and share tools for tractography analysis. Due to the high computational requirements, the most demanding modules were implemented in C/C++. Available functions include brain Bundle Segmentation (FiberSeg), Hierarchical Fiber Clustering (HClust), Fast Fiber Clustering (FFClust), normalization to a reference coordinate system, fiber sampling, calculation of intersection between sets of brain fibers, tools for cluster filtering, calculation of measures from clusters, and fiber visualization. The library tools were structured into four principal modules: Segmentation, Clustering, Utils, and Visualization (Fibervis). Phybers is freely available on a GitHub repository under the GNU public license for non-commercial use and open-source development, which provides sample data and extensive documentation. In addition, the library can be easily installed on both Windows and Ubuntu operating systems through the pip library.

Brain volumetric correlates of remotely versus in-person administered symbol digit modalities test in multiple sclerosis.

BACKGROUND: Prior studies in multiple sclerosis (MS) support reliability of telehealth-delivered cognitive batteries, although, to date, none have reported relationships of cognitive test performance to neural correlates across administration modalities. In this study we aimed to compare brain-behavior relationships, using the Symbol Digit Modalities Test (SDMT), the most reliable and sensitive cognitive measure in MS, measured from patients seen via telehealth versus in-person. METHODS: SDMT was administered to individuals with MS either in-person (N=60, mean age=39.7) or remotely via video conference (N=51, mean age=47.4). Magnetic resonance imaging (MRI) data was collected in 3-Tesla scanners. Using 3-dimensional T1 images cerebral, cortical, deep gray, cerebral white matter and thalamic nuclei volumes were calculated. Using a meta-analysis approach with an interaction term for participant group, individual regression models were run for each MRI measure having SDMT scores as the outcome variable in each model. In addition, the correlation and average difference between In-person and Remote group associations across the MRI measures were calculated. Finally, for each MRI variable I2 score was quantified to test the heterogeneity between the groups. RESULTS: Administration modality did not affect the association of SDMT performance with MRI measures. Brain tissue volumes showing high associations with the SDMT scores in one group also showed high associations in the other (r = 0.83; 95% CI = [0.07, 0.86]). The average difference between the In-person and the Remote group associations was not significant (ßRemote - ßIn-person = 0.14, 95% CI = [-0.04, 0.34]). Across MRI measures, the average I2 value was 14%, reflecting very little heterogeneity in the relationship of SDMT performance to brain volume. CONCLUSION: We found consistent relationships to neural correlates across in-person and remote SDMT administration modalities. Hence, our study extended the findings of the previous studies demonstrating the feasibility of remote administration of the SDMT.

Superficial white matter bundle atlas based on hierarchical fiber clustering over probabilistic tractography data.

The study of short association fibers is still an incomplete task due to their higher inter-subject variability and the smaller size of this kind of fibers in comparison to known long association bundles. However, their description is essential to understand human brain dysfunction and better characterize the human brain connectome. In this work, we present a multi-subject atlas of short association fibers, which was computed using a superficial white matter bundle identification method based on fiber clustering. To create the atlas, we used probabilistic tractography from one hundred subjects from the HCP database, aligned with non-linear registration. The method starts with an intra-subject clustering of short fibers (30-85 mm). Based on a cortical atlas, the intra-subject cluster centroids from all subjects are segmented to identify the centroids connecting each region of interest (ROI) of the atlas. To reduce computational load, the centroids from each ROI group are randomly separated into ten subgroups. Then, an inter-subject hierarchical clustering is applied to each centroid subgroup, followed by a second level of clustering to select the most-reproducible clusters across subjects for each ROI group. Finally, the clusters are labeled according to the regions that they connect, and clustered to create the final bundle atlas. The resulting atlas is composed of 525 bundles of superficial short association fibers along the whole brain, with 384 bundles connecting pairs of different ROIs and 141 bundles connecting portions of the same ROI. The reproducibility of the bundles was verified using automatic segmentation on three different tractogram databases. Results for deterministic and probabilistic tractography data show high reproducibility, especially for probabilistic tractography in HCP data. In comparison to previous work, our atlas features a higher number of bundles and greater cortical surface coverage.

Disentangling the variability of the superficial white matter organization using regional-tractogram-based population stratification.

Each variation of the cortical folding pattern implies a particular rearrangement of the geometry of the fibers of the underlying white matter. While this rearrangement only impacts the ends of the long pathways, it may affect most of the trajectory of the short bundles. Therefore, mapping the short fibers of the human brain using diffusion-based tractography requires a dedicated strategy to overcome the variability of the folding patterns. In this paper, we propose a fiber-based stratification strategy splitting the population into homogeneous groups for disentangling the superficial white matter bundle organization. This strategy introduces a new refined fiber distance which includes angular considerations for inferring fine-grained atlases of the short bundles surrounding a specific sulcus and a subtractogram distance that quantifies the similitude between fiber sets of two different subjects. The stratification splits the population into groups with similar regional fiber organization using manifold learning. We first successfully test the hypothesis that the main source of variability of the regional fiber organization is the variability of the regional folding pattern. Then, in each group, we proceed with the automatic identification of the most stable bundles, at a higher granularity level than what can be achieved with the non-stratified whole population, enabling the disentanglement of the very variable configuration of the short fibers. Finally, the method searches for bundle correspondence across groups to build a population level atlas. As a proof of concept, the atlas refinement achieved by this strategy is illustrated for the fibers that surround the central sulcus and the superior temporal sulcus using the HCP dataset.

Machine learning to investigate superficial white matter integrity in early multiple sclerosis.

BACKGROUND AND PURPOSE: This study aims todetermine the sensitivity of superficial white matter (SWM) integrity as a metric to distinguish early multiple sclerosis (MS) patients from healthy controls (HC). METHODS: Fractional anisotropy and mean diffusivity (MD) values from SWM bundles across the cortex and major deep white matter (DWM) tracts were extracted from 29 early MS patients and 31 age- and sex-matched HC. Thickness of 68 cortical regions and resting-state functional-connectivity (RSFC) among them were calculated. The distribution of structural and functional metrics between groups were compared using Wilcoxon rank-sum test. Utilizing a machine learning method (adaptive boosting), 6 models were built based on: 1-SWM, 2-DWM, 3-SWM and DWM, 4-cortical thickness, or 5-RSFC measures. In model 6, all features from previous models were incorporated. The models were trained with nested 5-folds cross-validation. Area under the receiver operating characteristic curve (AUCroc ) values were calculated to evaluate classification performance of each model. Permutation tests were used to compare the AUCroc values. RESULTS: Patients had higher MD in SWM bundles including insula, inferior frontal, orbitofrontal, superior and medial temporal, and pre- and post-central cortices (p < .05). No group differences were found for any other MRI metric. The model incorporating SWM and DWM features provided the best classification (AUCroc = 0.75). The SWM model provided higher AUCroc (0.74), compared to DWM (0.63), cortical thickness (0.67), RSFC (0.63), and all-features (0.68) models (p < .001 for all). CONCLUSION: Our results reveal a non-random pattern of SWM abnormalities at early stages of MS even before pronounced structural and functional alterations emerge.

Group-Wise Cortical Surface Parcellation Based on Inter-Subject Fiber Clustering.

We present an automatic algorithm for the group-wise parcellation of the cortical surface. The method is based on the structural connectivity obtained from representative brain fiber clusters, calculated via an inter-subject clustering scheme. Preliminary regions were defined from cluster-cortical mesh intersection points. The final parcellation was obtained using parcel probability maps to model and integrate the connectivity information of all subjects, and graphs to represent the overlap between parcels. Two inter-subject clustering schemes were tested, generating a total of 171 and 109 parcels, respectively. The resulting parcels were quantitatively compared with three state-of-the-art atlases. The best parcellation returned 69 parcels with a Dice similarity coefficient greater than 0.5. To the best of our knowledge, this is the first diffusion-based cortex parcellation method based on whole-brain inter-subject fiber clustering.

Fiber Clustering Acceleration With a Modified Kmeans++ Algorithm Using Data Parallelism.

Fiber clustering methods are typically used in brain research to study the organization of white matter bundles from large diffusion MRI tractography datasets. These methods enable exploratory bundle inspection using visualization and other methods that require identifying brain white matter structures in individuals or a population. Some applications, such as real-time visualization and inter-subject clustering, need fast and high-quality intra-subject clustering algorithms. This work proposes a parallel algorithm using a General Purpose Graphics Processing Unit (GPGPU) for fiber clustering based on the FFClust algorithm. The proposed GPGPU implementation exploits data parallelism using both multicore and GPU fine-grained parallelism present in commodity architectures, including current laptops and desktop computers. Our approach implements all FFClust steps in parallel, improving execution times in all of them. In addition, our parallel approach includes a parallel Kmeans++ algorithm implementation and defines a new variant of Kmeans++ to reduce the impact of choosing outliers as initial centroids. The results show that our approach provides clustering quality results very similar to FFClust, and it requires an execution time of 3.5 s for processing about a million fibers, achieving a speedup of 11.5 times compared to FFClust.

ABrainVis: an android brain image visualization tool.

BACKGROUND: The visualization and analysis of brain data such as white matter diffusion tractography and magnetic resonance imaging (MRI) volumes is commonly used by neuro-specialist and researchers to help the understanding of brain structure, functionality and connectivity. As mobile devices are widely used among users and their technology shows a continuous improvement in performance, different types of applications have been designed to help users in different work areas. RESULTS: We present, ABrainVis, an Android mobile tool that allows users to visualize different types of brain images, such as white matter diffusion tractographies, represented as fibers in 3D, segmented fiber bundles, MRI 3D images as rendered volumes and slices, and meshes. The tool enables users to choose and combine different types of brain imaging data to provide visual anatomical context for specific visualization needs. ABrainVis provides high performance over a wide range of Android devices, including tablets and cell phones using medium and large tractography datasets. Interesting visualizations including brain tumors and arteries, along with fiber, are given as examples of case studies using ABrainVis. CONCLUSIONS: The functionality, flexibility and performance of ABrainVis tool introduce an improvement in user experience enabling neurophysicians and neuroscientists fast visualization of large tractography datasets, as well as the ability to incorporate other brain imaging data such as MRI volumes and meshes, adding anatomical contextual information.

Disruption of Conscious Access in Psychosis Is Associated with Altered Structural Brain Connectivity.

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in long-distance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis.

Inter-Subject Clustering of Brain Fibers from Whole-Brain Tractography.

This work presents an effective multiple subject clustering method using whole-brain tractography datasets. The method is able to obtain fiber clusters that are representative of the population. The proposed approach first applies a fast intra-subject clustering algorithm on each subject obtaining the cluster centroids for all subjects. Second, it compresses the collection of centroids to a latent space through the encoder of a trained autoencoder. Finally, it uses a modified HDBSCAN with adjusted parameters on the encoded centroids of all subjects to obtain the final inter-subject clusters. The results shows that the proposed method outperforms other clustering strategies, and it is able to retrieve known fascicles in a reasonable execution time, achieving a precision over 87% and F1 score above 86% on a collection of 20 simulated subjects.

GeoSP: A parallel method for a cortical surface parcellation based on geodesic distance.

We present GeoSP, a parallel method that creates a parcellation of the cortical mesh based on a geodesic distance, in order to consider gyri and sulci topology. The method represents the mesh with a graph and performs a K-means clustering in parallel. It has two modes of use, by default, it performs the geodesic cortical parcellation based on the boundaries of the anatomical parcels provided by the Desikan-Killiany atlas. The other mode performs the complete parcellation of the cortex. Results for both modes and with different values for the total number of sub-parcels show homogeneous sub-parcels. Furthermore, the execution time is 82s for the whole cortex mode and 18s for the Desikan-Killiany atlas subdivision, for a parcellation into 350 sub-parcels. The proposed method will be available to the community to perform the evaluation of data-driven cortical parcellations. As an example, we compared GeoSP parcellation with Desikan-Killiany and Destrieux atlases in 50 subjects, obtaining more homogeneous parcels for GeoSP and minor differences in structural connectivity reproducibility across subjects.

From Coarse to Fine-Grained Parcellation of the Cortical Surface Using a Fiber-Bundle Atlas.

In this article, we present a hybrid method to create fine-grained parcellations of the cortical surface, from a coarse-grained parcellation according to an anatomical atlas, based on cortico-cortical connectivity. The connectivity information is obtained from segmented superficial and deep white matter bundles, according to bundle atlases, instead of the whole tractography. Thus, a direct matching between the fiber bundles and the cortical regions is obtained, avoiding the problem of finding the correspondence of the cortical parcels among subjects. Generating parcels from segmented fiber bundles can provide a good representation of the human brain connectome since they are based on bundle atlases that contain the most reproducible short and long connections found on a population of subjects. The method first processes the tractography of each subject and extracts the bundles of the atlas, based on a segmentation algorithm. Next, the intersection between the fiber bundles and the cortical mesh is calculated, to define the initial and final intersection points of each fiber. A fiber filtering is then applied to eliminate misclassified fibers, based on the anatomical definition of each bundle and the labels of Desikan-Killiany anatomical parcellation. A parcellation algorithm is then performed to create a subdivision of the anatomical regions of the cortex, which is reproducible across subjects. This step resolves the overlapping of the fiber bundle extremities over the cortical mesh within each anatomical region. For the analysis, the density of the connections and the degree of overlapping, is considered and represented with a graph. One of our parcellations, an atlas composed of 160 parcels, achieves a reproducibility across subjects of ≈0.74, based on the average Dice's coefficient between subject's connectivity matrices, rather than ≈0.73 obtained for a macro anatomical parcellation of 150 parcels. Moreover, we compared two of our parcellations with state-of-the-art atlases, finding a degree of similarity with dMRI, functional, anatomical, and multi-modal atlases. The higher similarity was found for our parcellation composed of 185 sub-parcels with another parcellation based on dMRI data from the same database, but created with a different approach, leading to 130 parcels in common based on a Dice's coefficient ≥0.5.

Automatic group-wise whole-brain short association fiber bundle labeling based on clustering and cortical surface information.

BACKGROUND: Diffusion MRI is the preferred non-invasive in vivo modality for the study of brain white matter connections. Tractography datasets contain 3D streamlines that can be analyzed to study the main brain white matter tracts. Fiber clustering methods have been used to automatically group similar fibers into clusters. However, due to inter-subject variability and artifacts, the resulting clusters are difficult to process for finding common connections across subjects, specially for superficial white matter. METHODS: We present an automatic method for labeling of short association bundles on a group of subjects. The method is based on an intra-subject fiber clustering that generates compact fiber clusters. Posteriorly, the clusters are labeled based on the cortical connectivity of the fibers, taking as reference the Desikan-Killiany atlas, and named according to their relative position along one axis. Finally, two different strategies were applied and compared for the labeling of inter-subject bundles: a matching with the Hungarian algorithm, and a well-known fiber clustering algorithm, called QuickBundles. RESULTS: Individual labeling was executed over four subjects, with an execution time of 3.6 min. An inspection of individual labeling based on a distance measure showed good correspondence among the four tested subjects. Two inter-subject labeling were successfully implemented and applied to 20 subjects and compared using a set of distance thresholds, ranging from a conservative value of 10 mm to a moderate value of 21 mm. Hungarian algorithm led to a high correspondence, but low reproducibility for all the thresholds, with 96 s of execution time. QuickBundles led to better correspondence, reproducibility and short execution time of 9 s. Hence, the whole processing for the inter-subject labeling over 20 subjects takes 1.17 h. CONCLUSION: We implemented a method for the automatic labeling of short bundles in individuals, based on an intra-subject clustering and the connectivity of the clusters with the cortex. The labels provide useful information for the visualization and analysis of individual connections, which is very difficult without any additional information. Furthermore, we provide two fast inter-subject bundle labeling methods. The obtained clusters could be used for performing manual or automatic connectivity analysis in individuals or across subjects.

FFClust: Fast fiber clustering for large tractography datasets for a detailed study of brain connectivity.

Automated methods that can identify white matter bundles from large tractography datasets have several applications in neuroscience research. In these applications, clustering algorithms have shown to play an important role in the analysis and visualization of white matter structure, generating useful data which can be the basis for further studies. This work proposes FFClust, an efficient fiber clustering method for large tractography datasets containing millions of fibers. Resulting clusters describe the whole set of main white matter fascicles present on an individual brain. The method aims to identify compact and homogeneous clusters, which enables several applications. In individuals, the clusters can be used to study the local connectivity in pathological brains, while at population level, the processing and analysis of reproducible bundles, and other post-processing algorithms can be carried out to study the brain connectivity and create new white matter bundle atlases. The proposed method was evaluated in terms of quality and execution time performance versus the state-of-the-art clustering techniques used in the area. Results show that FFClust is effective in the creation of compact clusters, with a low intra-cluster distance, while keeping a good quality Davies-Bouldin index, which is a metric that quantifies the quality of clustering approaches. Furthermore, it is about 8.6 times faster than the most efficient state-of-the-art method for one million fibers dataset. In addition, we show that FFClust is able to correctly identify atlas bundles connecting different brain regions, as an example of application and the utility of compact clusters.

Superficial white matter: A review on the dMRI analysis methods and applications.

The mapping of human brain connections is still an on going task. Unlike deep white matter (DWM), which has been extensively studied and well documented, superficial white matter (SWM) has been often left aside. Improving our understanding of the SWM is an important goal for a better understanding of the brain network and its relation to several pathologies. The shape and localization of these short bundles present a high variability across subjects. Furthermore, the small diameter of most superficial bundles and partial volume effects induced by their proximity to the cortex leads to complex tratography issues. Therefore, the mapping of SWM bundles and the use of the resulting atlases for clinical studies requiere dedicated methodologies that are reviewed in this paper.

Increased and Decreased Superficial White Matter Structural Connectivity in Schizophrenia and Bipolar Disorder.

Schizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as "disconnection syndromes," with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from postmortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labeling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal, and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory, and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.

A stringent fiber distance measure for dMRI tractography clustering and segmentation.

Most analysis and segmentation methods for diffusion MRI tractography datasets require a fiber distance measure able to determine the similarity between a pair of fibers. We present a stringent fiber distance measure able to perform a good discrimination between fiber shapes and lengths. It uses three terms: (i) a fiber maximum Euclidean distance, (ii) a fiber shape distance, and (iii) a fiber length distance. The distance was evaluated applying a hierarchical clustering of fibers connecting the pre-and post-central gyri of a subject. Results where compared with other known fiber distance measures. A better sensitivity to differences in fiber shape and length was found for the proposed distance. This will be very useful for the detailed study and description of white matter bundles. Known bundles will be better decomposed into sub-bundles, with more precision on the bundle shape and on the regions connected by the fibers. For short association bundles, this distance will be a real improvement, as even the most stringent distance used until now shows some limitations when evaluating the similarity of these fibers.

Local structural connectivity is associated with social cognition in autism spectrum disorder.

The current theory implying local, short-range overconnectivity in autism spectrum disorder, contrasting with long-range underconnectivity, is based on heterogeneous results, on limited data involving functional connectivity studies, on heterogeneous paediatric populations and non-specific methodologies. In this work, we studied short-distance structural connectivity in a homogeneous population of males with high-functioning autism spectrum disorder and used a novel methodology specifically suited for assessing U-shaped short-distance tracts, including a recently developed tractography-based atlas of the superficial white matter fibres. We acquired diffusion-weighted MRI for 58 males (27 subjects with high-functioning autism spectrum disorder and 31 control subjects) and extracted the mean generalized fractional anisotropy of 63 short-distance tracts. Neuropsychological evaluation included Wechsler Adult Intelligence Scale IV (WAIS-IV), Communication Checklist-Adult, Empathy Quotient, Social Responsiveness Scale and Behaviour Rating Inventory of Executive Function-Adult (BRIEF-A). In contradiction with the models of short-range over-connectivity in autism spectrum disorder, we found that patients with autism spectrum disorder had a significantly decreased anatomical connectivity in a component comprising 13 short tracts compared to controls. Specific short-tract atypicalities in temporal lobe and insula were significantly associated with clinical manifestations of autism spectrum disorder such as social awareness, language structure, pragmatic skills and empathy, emphasizing their importance in social dysfunction. Short-range decreased anatomical connectivity may thus be an important substrate of social deficits in autism spectrum disorder, in contrast with current models.