A Proposed Human Structural Brain Connectivity Matrix in the Center for Morphometric Analysis Harvard-Oxford Atlas Framework: A Historical Perspective and Future Direction for Enhancing the Precision of Human Structural Connectivity with a Novel Neuroanatomical Typology.

A complete structural definition of the human nervous system must include delineation of its wiring diagram (e.g., Swanson LW. Brain architecture: understanding the basic plan, 2012). The complete formulation of the human brain circuit diagram (BCD [Front Neuroanat. 2020;14:18]) has been hampered by an inability to determine connections in their entirety (i.e., not only pathway stems but also origins and terminations). From a structural point of view, a neuroanatomic formulation of the BCD should include the origins and terminations of each fiber tract as well as the topographic course of the fiber tract in three dimensions. Classic neuroanatomical studies have provided trajectory information for pathway stems and their speculative origins and terminations [Dejerine J and Dejerine-Klumpke A. Anatomie des Centres Nerveux, 1901; Dejerine J and Dejerine-Klumpke A. Anatomie des Centres Nerveux: Méthodes générales d'étude-embryologie-histogénèse et histologie. Anatomie du cerveau, 1895; Ludwig E and Klingler J. Atlas cerebri humani, 1956; Makris N. Delineation of human association fiber pathways using histologic and magnetic resonance methodologies; 1999; Neuroimage. 1999 Jan;9(1):18-45]. We have summarized these studies previously [Neuroimage. 1999 Jan;9(1):18-45] and present them here in a macroscale-level human cerebral structural connectivity matrix. A matrix in the present context is an organizational construct that embodies anatomical knowledge about cortical areas and their connections. This is represented in relation to parcellation units according to the Harvard-Oxford Atlas neuroanatomical framework established by the Center for Morphometric Analysis at Massachusetts General Hospital in the early 2000s, which is based on the MRI volumetrics paradigm of Dr. Verne Caviness and colleagues [Brain Dev. 1999 Jul;21(5):289-95]. This is a classic connectional matrix based mainly on data predating the advent of DTI tractography, which we refer to as the "pre-DTI era" human structural connectivity matrix. In addition, we present representative examples that incorporate validated structural connectivity information from nonhuman primates and more recent information on human structural connectivity emerging from DTI tractography studies. We refer to this as the "DTI era" human structural connectivity matrix. This newer matrix represents a work in progress and is necessarily incomplete due to the lack of validated human connectivity findings on origins and terminations as well as pathway stems. Importantly, we use a neuroanatomical typology to characterize different types of connections in the human brain, which is critical for organizing the matrices and the prospective database. Although substantial in detail, the present matrices may be assumed to be only partially complete because the sources of data relating to human fiber system organization are limited largely to inferences from gross dissections of anatomic specimens or extrapolations of pathway tracing information from nonhuman primate experiments [Front Neuroanat. 2020;14:18, Front Neuroanat. 2022;16:1035420, and Brain Imaging Behav. 2021;15(3):1589-1621]. These matrices, which embody a systematic description of cerebral connectivity, can be used in cognitive and clinical studies in neuroscience and, importantly, to guide research efforts for further elucidating, validating, and completing the human BCD [Front Neuroanat. 2020;14:18].

Quantitative MRI Characterization of the Extremely Preterm Brain at Adolescence: Atypical versus Neurotypical Developmental Pathways.

Background Extremely preterm (EP) birth is associated with higher risks of perinatal white matter (WM) injury, potentially causing abnormal neurologic and neurocognitive outcomes. MRI biomarkers distinguishing individuals with and without neurologic disorder guide research on EP birth antecedents, clinical correlates, and prognoses. Purpose To compare multiparametric quantitative MRI (qMRI) parameters of EP-born adolescents with autism spectrum disorder, cerebral palsy, epilepsy, or cognitive impairment (ie, atypically developing) with those without (ie, neurotypically developing), characterizing sex-stratified brain development. Materials and Methods This prospective multicenter study included individuals aged 14-16 years born EP (Extremely Low Gestational Age Newborns-Environmental Influences on Child Health Outcomes Study, or ELGAN-ECHO). Participants underwent 3.0-T MRI evaluation from 2017 to 2019. qMRI outcomes were compared for atypically versus neurotypically developing adolescents and for girls versus boys. Sex-stratified multiple regression models were used to examine associations between spatial entropy density (SEd) and T1, T2, and cerebrospinal fluid (CSF)-normalized proton density (nPD), and between CSF volume and T2. Interaction terms modeled differences in slopes between atypically versus neurotypically developing adolescents. Results A total of 368 adolescents were classified as 116 atypically (66 boys) and 252 neurotypically developing (125 boys) participants. Atypically versus neurotypically developing girls had lower nPD (mean, 557 10 × percent unit [pu] ± 46 [SD] vs 573 10 × pu ± 43; P = .04), while atypically versus neurotypically developing boys had longer T1 (814 msec ± 57 vs 789 msec ± 82; P = .01). Atypically developing girls versus boys had lower nPD and shorter T2 (eg, in WM, 557 10 × pu ± 46 vs 580 10 × pu ± 39 for nPD [P = .006] and 86 msec ± 3 vs 88 msec ± 4 for T2 [P = .003]). Atypically versus neurotypically developing boys had a more moderate negative association between T1 and SEd (slope, -32.0 msec per kB/cm3 [95% CI: -49.8, -14.2] vs -62.3 msec per kB/cm3 [95% CI: -79.7, -45.0]; P = .03). Conclusion Atypically developing participants showed sexual dimorphisms in the cerebrospinal fluid-normalized proton density (nPD) and T2 of both white matter (WM) and gray matter. Atypically versus neurotypically developing girls had lower WM nPD, while atypically versus neurotypically developing boys had longer WM T1 and more moderate T1 associations with microstructural organization in WM. © RSNA, 2022 Online supplemental material is available for this article.

Meaningful associations in the adolescent brain cognitive development study.

The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and children's health in the United States. A cohort of n = 11,880 children aged 9-10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basis for at least 10 years. The study approximates the US population on several key sociodemographic variables, including sex, race, ethnicity, household income, and parental education. Data collected include assessments of health, mental health, substance use, culture and environment and neurocognition, as well as geocoded exposures, structural and functional magnetic resonance imaging (MRI), and whole-genome genotyping. Here, we describe the ABCD Study aims and design, as well as issues surrounding estimation of meaningful associations using its data, including population inferences, hypothesis testing, power and precision, control of covariates, interpretation of associations, and recommended best practices for reproducible research, analytical procedures and reporting of results.

New human-specific brain landmark: the depth asymmetry of superior temporal sulcus.

Identifying potentially unique features of the human cerebral cortex is a first step to understanding how evolution has shaped the brain in our species. By analyzing MR images obtained from 177 humans and 73 chimpanzees, we observed a human-specific asymmetry in the superior temporal sulcus at the heart of the communication regions and which we have named the "superior temporal asymmetrical pit" (STAP). This 45-mm-long segment ventral to Heschl's gyrus is deeper in the right hemisphere than in the left in 95% of typical human subjects, from infanthood till adulthood, and is present, irrespective of handedness, language lateralization, and sex although it is greater in males than in females. The STAP also is seen in several groups of atypical subjects including persons with situs inversus, autistic spectrum disorder, Turner syndrome, and corpus callosum agenesis. It is explained in part by the larger number of sulcal interruptions in the left than in the right hemisphere. Its early presence in the infants of this study as well as in fetuses and premature infants suggests a strong genetic influence. Because this asymmetry is barely visible in chimpanzees, we recommend the STAP region during midgestation as an important phenotype to investigate asymmetrical variations of gene expression among the primate lineage. This genetic target may provide important insights regarding the evolution of the crucial cognitive abilities sustained by this sulcus in our species, namely communication and social cognition.

Making replication prestigious.

Making replication studies widely conducted and published requires new incentives. Academic awards can provide such incentives by highlighting the best and most important replications. The Organization for Human Brain Mapping (OHBM) has led such efforts by recently introducing the OHBM Replication Award. Other communities can adopt this approach to promote replications and reduce career cost for researchers performing them.

Rhythmic Interlimb Coordination Impairments Are Associated With Mobility Limitations Among Older Adults.

Background/Study Context: Mobility limitations affect more than 25% of adults aged 70 years or older. This study tested the hypothesis that impairments in ankle and shoulder coordination are associated with mobility limitations among older adults. METHODS: his study consisted of conducted a cross-sectional analysis from a sample of community-dwelling older adults (N = 130) aged ≥67 years. Motion capture equipment was used to collect kinematic data during rhythmic antiphase coordination of the right and left: (a) ankles moving in dorsi-plantarflexion; and (b) glenohumeral ("shoulder") moving in flexion-extension while paced by an auditory metronome. Coordination variability was measured as the standard deviation of the relative phase between right and left body segments. Mobility limitations were defined as a score of ≤9 on the Short Physical Performance Battery (SPPB). Odds ratios for mobility limitations as a function of coordination variability quartiles were determined using multivariable logistic regression. RESULTS: Adjusting for age, gender, body mass index, number of chronic conditions and Mini-Mental State Examination score, the odds ratios for mobility limitation (SPPB score ≤9) were 7.38 (95% confidence interval [CI]: 2.20-24.78) and 15.40 (95% CI: 4.31-55.07) for the 3rd and 4th (the poorest) ankle coordination quartiles, respectively, and 6.73 (95% CI: 2.11-21.51) for the 4th shoulder coordination quartile, compared with the best (the 1st) coordination quartiles. CONCLUSION: The results supported the hypothesis that impaired interlimb ankle and shoulder coordination are associated with the manifestation of mobility limitations. These findings indicate the need for further study of the role of coordination impairments as potential contributors to poor mobility among older adults.

Coordination Impairments Are Associated With Falling Among Older Adults.

Background/Study Context: Approximately one third of older adults over the age of 65, and over 40% of those over 80 years, fall each year, leading to fractures, morbidity, and mortality. Annual direct medical costs due to falls in the United States are approximately $19.2 billion. The identification of new treatable risk factors for falls has the potential to advance their prevention and rehabilitation. METHODS: A cross-sectional study of 127 community-dwelling adults aged 67-99 years was conducted. An electronic gait walkway was used to assess gait coordination, measured as the Phase Coordination Index during normal speed walking. A motion capture system was used to assess rhythmic interlimb antiphase ankle coordination, measured as the standard deviation of ankle relative phase. Having fallen in the previous year was self-reported retrospectively. Odds ratios for falling as a function of coordination quartiles were determined using multivariable logistic regression. RESULTS: Adjusting for age, sex, body mass index, number of chronic conditions, Mini-Mental State Examination score, gait speed, and the variability of step length, time, and width, the odds ratios for falling based upon being in the 4th (the poorest) quartiles of gait or ankle coordination were 5.5 (95% confidence interval [CI]: 1.2-24.7) and 8.2 (95% CI: 2.2-31.3), respectively, and 3.7 (95% CI: 1.0-13.8) for the 3rd quartile of gait coordination, compared with the best (the 1st) coordination quartiles. Similar results were found in regression without adjustment for gait characteristics. CONCLUSION: The results support the hypothesis that impaired gait and rhythmic interlimb ankle coordination are associated with a history of falls in the past year. Prospective longitudinal research is needed to determine the possible direction of causality between falls and impaired coordination.

The NITRC image repository.

The Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC - www.nitrc.org) suite of services include a resources registry, image repository and a cloud computational environment to meet the needs of the neuroimaging researcher. NITRC provides image-sharing functionality through both the NITRC Resource Registry (NITRC-R), where bulk data files can be released through the file release system (FRS), and the NITRC Image Repository (NITRC-IR), a XNAT-based image data management system. Currently hosting 14 projects, 6845 subjects, and 8285 MRI imaging sessions, NITRC-IR provides a large array of structural, diffusion and resting state MRI data. Designed to be flexible about management of data access policy, NITRC provides a simple, free, NIH-funded service to support resource sharing in general, and image sharing in particular.

The Pediatric Imaging, Neurocognition, and Genetics (PING) Data Repository.

The main objective of the multi-site Pediatric Imaging, Neurocognition, and Genetics (PING) study was to create a large repository of standardized measurements of behavioral and imaging phenotypes accompanied by whole genome genotyping acquired from typically-developing children varying widely in age (3 to 20 years). This cross-sectional study produced sharable data from 1493 children, and these data have been described in several publications focusing on brain and cognitive development. Researchers may gain access to these data by applying for an account on the PING portal and filing a data use agreement. Here we describe the recruiting and screening of the children and give a brief overview of the assessments performed, the imaging methods applied, the genetic data produced, and the numbers of cases for whom different data types are available. We also cite sources of more detailed information about the methods and data. Finally we describe the procedures for accessing the data and for using the PING data exploration portal.

Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans.

Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.

Comparison of comprehensive quantitative EEG metrics between typically developing boys and girls in resting state eyes-open and eyes-closed conditions.

Introduction: A majority of published studies comparing quantitative EEG (qEEG) in typically developing (TD) children and children with neurodevelopmental or psychiatric disorders have used a control group (e.g., TD children) that combines boys and girls. This suggests a widespread supposition that typically developing boys and girls have similar brain activity at all locations and frequencies, allowing the data from TD boys and girls to be aggregated in a single group. Methods: In this study, we have rigorously challenged this assumption by performing a comprehensive qEEG analysis on EEG recoding of TD boys (n = 84) and girls (n = 62), during resting state eyes-open and eyes-closed conditions (EEG recordings from Child Mind Institute's Healthy Brain Network (HBN) initiative). Our qEEG analysis was performed over narrow-band frequencies (e.g., separating low α from high α, etc.), included sex, age, and head size as covariates in the analysis, and encompassed computation of a wide range of qEEG metrics that included both absolute and relative spectral power levels, regional hemispheric asymmetry, and inter- and intra-hemispheric magnitude coherences as well as phase coherency among cortical regions. We have also introduced a novel compact yet comprehensive visual presentation of the results that allows comparison of the qEEG metrics of boys and girls for the entire EEG locations, pairs, and frequencies in a single graph. Results: Our results show there are wide-spread EEG locations and frequencies where TD boys and girls exhibit differences in their absolute and relative spectral powers, hemispheric power asymmetry, and magnitude coherence and phase synchrony. Discussion: These findings strongly support the necessity of including sex, age, and head size as covariates in the analysis of qEEG of children, and argue against combining data from boys and girls. Our analysis also supports the utility of narrow-band frequencies, e.g., dividing α, ß, and γ band into finer sub-scales. The results of this study can serve as a comprehensive normative qEEG database for resting state studies in children containing both eyes open and eyes closed paradigms.

NIDM-Terms: community-based terminology management for improved neuroimaging dataset descriptions and query.

The biomedical research community is motivated to share and reuse data from studies and projects by funding agencies and publishers. Effectively combining and reusing neuroimaging data from publicly available datasets, requires the capability to query across datasets in order to identify cohorts that match both neuroimaging and clinical/behavioral data criteria. Critical barriers to operationalizing such queries include, in part, the broad use of undefined study variables with limited or no annotations that make it difficult to understand the data available without significant interaction with the original authors. Using the Brain Imaging Data Structure (BIDS) to organize neuroimaging data has made querying across studies for specific image types possible at scale. However, in BIDS, beyond file naming and tightly controlled imaging directory structures, there are very few constraints on ancillary variable naming/meaning or experiment-specific metadata. In this work, we present NIDM-Terms, a set of user-friendly terminology management tools and associated software to better manage individual lab terminologies and help with annotating BIDS datasets. Using these tools to annotate BIDS data with a Neuroimaging Data Model (NIDM) semantic web representation, enables queries across datasets to identify cohorts with specific neuroimaging and clinical/behavioral measurements. This manuscript describes the overall informatics structures and demonstrates the use of tools to annotate BIDS datasets to perform integrated cross-cohort queries.

Biomarkers Based on Comprehensive Hierarchical EEG Coherence Analysis: Example Application to Social Competence in Autism (Preliminary Results).

Electroencephalography (EEG) coherence analysis, based on measurement of synchronous oscillations of neuronal clusters, has been used extensively to evaluate functional connectivity in brain networks. EEG coherence studies have used a variety of analysis variables (e.g., time and frequency resolutions corresponding to the analysis time period and frequency bandwidth), regions of the brain (e.g., connectivity within and between various cortical lobes and hemispheres) and experimental paradigms (e.g., resting state with eyes open or closed; performance of cognitive tasks). This variability in study designs has resulted in difficulties in comparing the findings from different studies and assimilating a comprehensive understanding of the underlying brain activity and regions with abnormal functional connectivity in a particular disorder. In order to address the variability in methods across studies and to facilitate the comparison of research findings between studies, this paper presents the structure and utilization of a comprehensive hierarchical electroencephalography (EEG) coherence analysis that allows for formal inclusion of analysis duration, EEG frequency band, cortical region, and experimental test condition in the computation of the EEG coherences. It further describes the method by which this EEG coherence analysis can be utilized to derive biomarkers related to brain (dys)function and abnormalities. In order to document the utility of this approach, the paper describes the results of the application of this method to EEG and behavioral data from a social synchrony paradigm in a small cohort of adolescents with and without Autism Spectral Disorder.

Is Neuroscience FAIR? A Call for Collaborative Standardisation of Neuroscience Data.

In this perspective article, we consider the critical issue of data and other research object standardisation and, specifically, how international collaboration, and organizations such as the International Neuroinformatics Coordinating Facility (INCF) can encourage that emerging neuroscience data be Findable, Accessible, Interoperable, and Reusable (FAIR). As neuroscientists engaged in the sharing and integration of multi-modal and multiscale data, we see the current insufficiency of standards as a major impediment in the Interoperability and Reusability of research results. We call for increased international collaborative standardisation of neuroscience data to foster integration and efficient reuse of research objects.

A Standards Organization for Open and FAIR Neuroscience: the International Neuroinformatics Coordinating Facility.

There is great need for coordination around standards and best practices in neuroscience to support efforts to make neuroscience a data-centric discipline. Major brain initiatives launched around the world are poised to generate huge stores of neuroscience data. At the same time, neuroscience, like many domains in biomedicine, is confronting the issues of transparency, rigor, and reproducibility. Widely used, validated standards and best practices are key to addressing the challenges in both big and small data science, as they are essential for integrating diverse data and for developing a robust, effective, and sustainable infrastructure to support open and reproducible neuroscience. However, developing community standards and gaining their adoption is difficult. The current landscape is characterized both by a lack of robust, validated standards and a plethora of overlapping, underdeveloped, untested and underutilized standards and best practices. The International Neuroinformatics Coordinating Facility (INCF), an independent organization dedicated to promoting data sharing through the coordination of infrastructure and standards, has recently implemented a formal procedure for evaluating and endorsing community standards and best practices in support of the FAIR principles. By formally serving as a standards organization dedicated to open and FAIR neuroscience, INCF helps evaluate, promulgate, and coordinate standards and best practices across neuroscience. Here, we provide an overview of the process and discuss how neuroscience can benefit from having a dedicated standards body.

A Bayesian model of shape and appearance for subcortical brain segmentation.

Automatic segmentation of subcortical structures in human brain MR images is an important but difficult task due to poor and variable intensity contrast. Clear, well-defined intensity features are absent in many places along typical structure boundaries and so extra information is required to achieve successful segmentation. A method is proposed here that uses manually labelled image data to provide anatomical training information. It utilises the principles of the Active Shape and Appearance Models but places them within a Bayesian framework, allowing probabilistic relationships between shape and intensity to be fully exploited. The model is trained for 15 different subcortical structures using 336 manually-labelled T1-weighted MR images. Using the Bayesian approach, conditional probabilities can be calculated easily and efficiently, avoiding technical problems of ill-conditioned covariance matrices, even with weak priors, and eliminating the need for fitting extra empirical scaling parameters, as is required in standard Active Appearance Models. Furthermore, differences in boundary vertex locations provide a direct, purely local measure of geometric change in structure between groups that, unlike voxel-based morphometry, is not dependent on tissue classification methods or arbitrary smoothing. In this paper the fully-automated segmentation method is presented and assessed both quantitatively, using Leave-One-Out testing on the 336 training images, and qualitatively, using an independent clinical dataset involving Alzheimer's disease. Median Dice overlaps between 0.7 and 0.9 are obtained with this method, which is comparable or better than other automated methods. An implementation of this method, called FIRST, is currently distributed with the freely-available FSL package.

Understanding the impact of preprocessing pipelines on neuroimaging cortical surface analyses.

BACKGROUND: The choice of preprocessing pipeline introduces variability in neuroimaging analyses that affects the reproducibility of scientific findings. Features derived from structural and functional MRI data are sensitive to the algorithmic or parametric differences of preprocessing tasks, such as image normalization, registration, and segmentation to name a few. Therefore it is critical to understand and potentially mitigate the cumulative biases of pipelines in order to distinguish biological effects from methodological variance. METHODS: Here we use an open structural MRI dataset (ABIDE), supplemented with the Human Connectome Project, to highlight the impact of pipeline selection on cortical thickness measures. Specifically, we investigate the effect of (i) software tool (e.g., ANTS, CIVET, FreeSurfer), (ii) cortical parcellation (Desikan-Killiany-Tourville, Destrieux, Glasser), and (iii) quality control procedure (manual, automatic). We divide our statistical analyses by (i) method type, i.e., task-free (unsupervised) versus task-driven (supervised); and (ii) inference objective, i.e., neurobiological group differences versus individual prediction. RESULTS: Results show that software, parcellation, and quality control significantly affect task-driven neurobiological inference. Additionally, software selection strongly affects neurobiological (i.e. group) and individual task-free analyses, and quality control alters the performance for the individual-centric prediction tasks. CONCLUSIONS: This comparative performance evaluation partially explains the source of inconsistencies in neuroimaging findings. Furthermore, it underscores the need for more rigorous scientific workflows and accessible informatics resources to replicate and compare preprocessing pipelines to address the compounding problem of reproducibility in the age of large-scale, data-driven computational neuroscience.

White matter volume abnormalities and associations with symptomatology in schizophrenia.

The cerebral white matter (WM) is critically involved in many bio-behavioral functions impaired in schizophrenia. However, the specific neural systems underlying symptomatology in schizophrenia are not well known. By comparing the volume of all brain fiber systems between chronic patients with DSM-III-R schizophrenia (n=88) and matched healthy community controls (n=40), we found that a set of a priori WM regions of local and distal associative fiber systems was significantly different in patients with schizophrenia. There were significant positive correlations between volumes (larger) in anterior callosal, cingulate and temporal deep WM regions (related to distal connections) with positive symptoms, such as hallucinations, delusions and bizarre behavior, and significant negative correlation between volumes (smaller) in occipital and paralimbic superficial WM (related to local connections) and posterior callosal fiber systems with higher negative symptoms, such as alogia. Furthermore, the temporal sagittal system showed significant rightward asymmetry between patients and controls. These observations suggest a pattern of volume WM alterations associated with symptomatology in schizophrenia that may be related in part to predisposition to schizophrenia.

Delineation of the middle longitudinal fascicle in humans: a quantitative, in vivo, DT-MRI study.

Experimental and imaging studies in monkeys have outlined various long association fiber bundles within the temporoparietal region. In the present study the trajectory of the middle longitudinal fascicle (MdLF) has been delineated in 4 human subjects using diffusion tensor magnetic resonance imaging segmentation and tractography. The MdLF seems to extend from the inferior parietal lobule (IPL), specifically the angular gyrus, to the temporal pole remaining within the white matter of the superior temporal gyrus (STG). Comparison of the superior longitudinal fascicle II-arcuate fascicle (SLF II-AF) with the MdLF in the same subjects revealed that MdLF is located in a medial and caudal position relative to SLF II-AF and that it extends more rostrally. Given the location of MdLF between the IPL (angular gyrus) and the STG, it is suggested that MdLF could have a role in language and attention functions.