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Representation of the left superior longitudinal fasciculus (SLF) subdivided into three branches. Branches are illustrated in three colours: SLF I (green), II (blue) and III (purple) in a representative subject.
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Core features of ASD may be underpinned by disrupted functional and structural neural connectivity. Abnormal fronto-parietal functional connectivity has been widely reported in the literature; this may be underpinned by disrupted microstructural organisation of white matter. The Superior Longitudinal Fasciculus (SLF) is a major fronto-parietal whit...
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Context 1
... CSD-based tractography algorithm extracted all fibre trajecto- ries which passed through the specified 'AND' gates and eliminated the pathways which went through the temporal 'NOT' gate to pro- duce the SLF I, II and III (Fig. 2). Individual tracts were visually inspected for each subject and edited where necessary. In the event that a tract did not appear to have been isolated as expected, the warped templates and ROIs for that subject were visualised to deter- mine which ROI(s) did not warp correctly. These ROI(s) were redrawn and the tract was isolated ...
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The aim of the present study is to investigate the development of visuospatial attention in typically developing children and to propose reference values for children for the following six visuospatial attention tests: star cancellation, Ogden figure, reading test, line bisection, proprioceptive pointing and visuo-proprioceptive pointing. Data of 1...
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... Altered FA in the left and right SLF has commonly been reported in ASD, a neurodevelopmental disorder characterized by deficits in social communication and social interaction. Studies in ASD samples found both increased and decreased FA (for an overview, see Fitzgerald et al., 2018). Moreover, lower FA values in the left SLF in ASD have been associated with reduced social cognition (Im et al., 2018). ...
Children born very preterm (VPT, < 32 weeks of gestation) have an increased risk of developing socio-emotional difficulties. Possible neural substrates for these socio-emotional difficulties are alterations in the structural connectivity of the social brain due to premature birth. The objective of the current study was to study microstructural white matter integrity in VPT versus full-term (FT) born school-aged children along twelve white matter tracts involved in socio-emotional processing. Diffusion MRI scans were obtained from a sample of 35 VPT and 38 FT 8-to-12-year-old children. Tractography was performed using TractSeg, a state-of-the-art neural network-based approach, which offers investigation of detailed tract profiles of fractional anisotropy (FA). Group differences in FA along the tracts were investigated using both a traditional and complementary functional data analysis approach. Exploratory correlations were performed between the Social Responsiveness Scale (SRS-2), a parent-report questionnaire assessing difficulties in social functioning, and FA along the tract. Both analyses showed significant reductions in FA for the VPT group along the middle portion of the right SLF I and an anterior portion of the left SLF II. These group differences possibly indicate altered white matter maturation due to premature birth and may contribute to altered functional connectivity in the Theory of Mind network which has been documented in earlier work with VPT samples. Apart from reduced social motivation in the VPT group, there were no significant group differences in reported social functioning, as assessed by SRS-2. We found that in the VPT group higher FA values in segments of the left SLF I and right SLF II were associated with better social functioning. Surprisingly, the opposite was found for segments in the right IFO, where higher FA values were associated with worse reported social functioning. Since no significant correlations were found for the FT group, this relationship may be specific for VPT children. The current study overcomes methodological limitations of previous studies by more accurately segmenting white matter tracts using constrained spherical deconvolution based tractography, by applying complementary tractometry analysis approaches to estimate changes in FA more accurately, and by investigating the FA profile along the three components of the SLF.
... To analyze the subcomponents of SLF, fibers in SLF need to be further segmented. Based on the axonal tracing results of monkey brains, in vivo dissection of SLF was adapted to human brains (31,32): two different ROIs ( Figure 1A) are defined on the same coronal slice at the anterior commissure (AC). A common ROI ( Figure 1B) was drawn on the coronal slice at the posterior commissure (PC). ...
The superior longitudinal fasciculus (SLF) is a major fiber tract involved in language processing and has been used to investigate language impairments and plasticity in many neurological diseases. The SLF is divided into four main branches that connect with different cortex regions, with two branches (SLF II, SLF III) being directly related to language. However, most white matter analyses consider the SLF as a single bundle, which may underestimate the relationship between these fiber bundles and language function. In this study, we investigated the differences between branches of the SLF in patients with arteriovenous malformation (AVM), which is a unique model to investigate language reorganization. We analyzed diffusion tensor imaging data of AVM patients and healthy controls to generate whole-brain fiber tractography, and then segmented the SLF into SLF II and III based on their distinctive waypoint regions. The SLF, SLF II, and III were further quantified, and four diffusion parameters of three branches were compared between the AVMs and controls. No significant diffusivity differences of the whole SLF were observed between two groups, however, the right SLF II and III in AVMs showed significant reorganization or impairment patterns as compared to the controls. Results demonstrating the need to subtracting SLF branches when studying structure-function relationship in neurological diseases that have SLF damage.
... SLF subcomponent masks (SLF I, SLF II, SLF III, and AF) were drawn using the freehand paint tool (intraclass correlation coefficient > 0.95 for all subcomponents). The branches of the SLF were isolated according to well-validated definitions in previous studies 59,60 (Fig. 4). AF was defined as fibers that did not pass through the anterior-posterior commissure line at the temporal lobe of the axial plane. ...
Although the potential role of superior longitudinal fasciculus (SLF) in intellectual deficits and treatment response (TR) in patients with schizophrenia (SZ) has been previously described, little is known about the white-matter (WM) integrity of SLF subcomponents (SLF I, II, III, and arcuate fasciculus) and their particular relationships with the clinical presentations of the illness. This study examined the associations between fractional anisotropy (FA) of SLF subcomponents and intelligence level and 6-month treatment response (TR) of negative symptoms (NS) in patients with SZ. At baseline, 101 patients with SZ and 101 healthy controls (HCs) underwent structural magnetic resonance imaging. Voxel-wise group comparison analysis showed significant SLF FA reductions in patients with SZ compared with HCs. Voxel-wise correlation analyses revealed significant positive correlations of FAs of right SLF II with Korean–Wechsler Adult Intelligence Scale at baseline and the percentage reduction of negative syndrome subscale of the Positive and Negative Syndrome Scales at 6 months. These findings suggest that aberrance in WM microstructure in SLF II may be associated with intellectual deficits in patients with SZ and TR of NS, which may support the potential role of SLF II as a novel neuroimaging biomarker for clinical outcomes of the illness.
... Previous studies have suggested that microstructural alterations in SLF sub-bundles are related to some neurodevelopmental and cognitive disorders. For example, greater fractional anisotropy (FA) of the right SLF II has been observed in the autism spectrum disorder (ASD) group (Fitzgerald et al. 2018), and higher axial diffusivity (AD) of the SLF I has been observed in individuals with attention deficit/hyperactivity disorder (ADHD) (Chiang et al. 2020). Hence, a segmentation study of the SLF and the morphological and microstructural exploration of each sub-bundle using diffusion MRI (dMRI) may be helpful for detecting cryptic white matter (WM) injury in neuropsychiatric disorders. ...
The superior longitudinal fasciculus (SLF) is a complex associative tract comprising three distinct subdivisions in the frontoparietal cortex, each of which has its own anatomical connectivity and functional roles. However, many studies on white matter development, hampered by limitations of data quality and tractography methods, treated the SLF as a single entity. The exact anatomical trajectory and developmental status of each sub-bundle of the human SLF in neonates remain poorly understood. Here, we compared the morphological and microstructural characteristics of each branch of the SLF at two ages using diffusion MRI data from 40 healthy neonates and 40 adults. A multi-shell multi-tissue constrained spherical deconvolution (MSMT-CSD) algorithm was used to ensure the successful separation of the three SLF branches (SLF I, SLF II and SLF III). Then, between-group differences in the diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics were investigated in all the SLF branches. Meanwhile, Mahalanobis distances based on all the diffusion metrics were computed to quantify the maturation of neonatal SLF branches, considering the adult brain as the reference. The SLF branches, excluding SLF II, had similar fibre morphology and connectivity between the neonatal and adult groups. The Mahalanobis distance values further supported the notion of heterogeneous maturation among SLF branches. The greatest Mahalanobis distance was observed in SLF II, possibly indicating that it was the least mature. Our findings provide a new anatomical basis for the early diagnosis and treatment of diseases caused by abnormal neonatal SLF development.
... Some studies demonstrated no significant difference in FA or MD in these tracts (such as AF, SLF, and UF) between the ASD and TD groups (Karahano glu et al., 2018;Liu et al., 2019). Several studies have found increased FA or reduced MD in the AF, IFOF, and SLF in the ASD group (Fitzgerald et al., 2018;Wolff et al., 2012). These inconsistent findings are likely related to variations in the characteristics of participants (e.g., sex, age, cognitive ability, symptom severity) and methodological approaches (e.g., data acquisition, analytic pipeline), as well as anatomical factors (e.g., hemisphere) among individual studies. ...
... Furthermore, numerous lines of evidence have shown atypical asymmetry of structural and functional brain organization in patients with ASD. For example, ASD individuals showed significantly less left-lateralization than TD controls in DTI metrics of the language-related tracts, such as AF (Fitzgerald et al., 2018;Joseph et al., 2014), SLF, ILF, and IFOF (Carper et al., 2016). Several DTI studies have reported right-lateralization in widespread white matter regions (Fu et al., 2020), including the AF (Wan et al., 2012). ...
Patients with autism spectrum disorder (ASD) often show pervasive and complex language impairments that are closely associated with aberrant structural connectivity of language networks. However, the characteristics of white matter connectivity in ASD have remained inconclusive in previous diffusion tensor imaging (DTI) studies. The current meta‐analysis aimed to comprehensively elucidate the abnormality in language‐related white matter connectivity in individuals with ASD. We searched PubMed, Web of Science, Scopus, and Medline databases to identify relevant studies. The standardized mean difference was calculated to measure the pooled difference in DTI metrics in each tract between the ASD and typically developing (TD) groups. The moderating effects of age, sex, language ability, and symptom severity were investigated using subgroup and meta‐regression analysis. Thirty‐three DTI studies involving 831 individuals with ASD and 836 TD controls were included in the meta‐analysis. ASD subjects showed significantly lower fractional anisotropy or higher mean diffusivity across language‐associated tracts than TD controls. These abnormalities tended to be more prominent in the left language networks than in the right. In addition, children with ASD exhibit more pronounced and pervasive disturbances in white matter connectivity than adults. These results support the under‐connectivity hypothesis and demonstrate the widespread abnormal microstructure of language‐related tracts in patients with ASD. Otherwise, white matter abnormalities in the autistic brain could vary depending on the developmental stage and hemisphere.
Lay Summary
This meta‐analysis explored abnormalities in white matter connectivity in language networks of individuals with ASD. Significantly reduced white matter integrity was found in all language‐associated tracts in subjects with ASD compared with TD controls. In addition, structural disturbances of language networks in the autistic brain exhibit a leftward tendency, and more prominent abnormalities are observed in younger people with ASD than in adults.
... It is of particular interest that right SLF-I specifically related to autism symptoms, as white matter findings in idiopathic ASD in this tract are highly variable. Indeed, both increased (Cheung et al., 2009;Weinstein et al., 2011;Fitzgerald et al., 2018) and decreased (Fitzgerald et al., 2019;Poustka et al., 2012;Im et al., 2018;Barnea-Goraly et al., 2010;Kleinhans et al., 2012) structural connectivity within left and right SLF have been observed in ASD, although studies typically do not differentiate between the three branches of the SLF. Importantly however, several studies in idiopathic ASD have shown that reduced fractional anisotropy in right SLF was associated with autism spectrum social communication difficulties (Poustka et al., 2012), autism quotient (Bakhtiari et al., 2012), and RRB (Fitzgerald et al., 2019). ...
Tuberous sclerosis complex is a rare genetic multisystem condition that is associated with a high prevalence of neurodevelopmental disorders such as autism and attention-deficit/hyperactivity disorder. The underlying neural mechanisms of the emergence of these symptom domains in tuberous sclerosis complex remain unclear.
Here, we use fixel-based analysis of diffusion-weighted imaging, which allows for the differentiation between multiple fibre populations within a voxel, to compare white matter properties in 16 participants with tuberous sclerosis complex (aged 11-19) and 12 age and sex matched control participants. We further tested associations between white matter alterations and autism and inattention symptoms as well as cognitive ability in participants with tuberous sclerosis complex.
Compared to controls, participants with tuberous sclerosis complex showed reduced fibre density cross-section (FDC) in the dorsal branch of right superior longitudinal fasciculus and bilateral inferior longitudinal fasciculus, reduced fibre density (FD) in bilateral tapetum, and reduced fibre cross-section (FC) in the ventral branch of right superior longitudinal fasciculus. In participants with tuberous sclerosis complex, the extent of FDC reductions in right superior longitudinal fasciculus was significantly associated with autism traits (social communication difficulties and restricted, repetitive behaviours), whereas FDC reductions in right inferior longitudinal fasciculus were associated with inattention. The observed white matter alterations were unrelated to cognitive ability.
Our findings shed light on the fibre-specific biophysical properties of white matter alterations in tuberous sclerosis complex and suggest that these regional changes are selectively associated with the severity of neurodevelopmental symptoms.
... While structurally defined sub-bundles still contain many streamlines, they are likely to be more homogenous than the entire bundle. Interestingly, analyses of the functional relevancy of the structural sub-bundles of the SLF suggest that they show different development trajectories and may be differentially impacted in different cognitive disorders (Galantucci et al. 2011;Thiebaut de Schotten et al. 2011;Parlatini et al. 2017;Fitzgerald et al. 2018;Amemiya et al. 2021). Other examples of structurally defined sub-bundles include: (1) the optic radiation, which contains an anterior sub-bundle that includes Meyer's loop, which has different structural properties than the rest of the bundle (Schurr et al. 2018), and (2) the anterior limb of the internal capsule, which in both non-human primates and humans contains distinct sub-bundles which vary in their connectivity to different parts of cortex (Safadi et al. 2018). ...
For over a century, researchers have examined the functional relevancy of white matter bundles. Consequently, many large-scale bundles spanning several centimeters have been associated in their entirety with specific brain functions, such as language or attention. However, these coarse structural–functional relationships are at odds with modern understanding of the fine-grained functional organization of human cortex, such as the mosaic of category-selective regions in ventral temporal cortex. Here, we review a multimodal approach that combines fMRI to define functional regions of interest within individual’s brains with dMRI tractography to identify the white matter bundles of the same individual. Combining these data allows to determine which subsets of streamlines within a white matter bundle connect to specific functional regions in each individual. That is, this approach identifies the functionally defined white matter sub-bundles of the brain. We argue that this approach not only enhances the accuracy of interpreting the functional relevancy of white matter bundles, but also enables segmentation of these large-scale bundles into meaningful functional units, which can then be linked to behavior with enhanced precision. Importantly, this approach has the potential for making new discoveries of the fine-grained functional relevancy of white matter connections in the visual system and the brain more broadly, akin to the flurry of research that has identified functional regions in cortex.
... The detailed methodology for Cingulum segmentation was derived from Wakana et al. (80). The detailed methodology for SLF I, II, and III segmentation, as well as AF segmentation, was emulated from Fitzgerald et al. (81). ...
The superior longitudinal fasciculus (SLF) is part of the longitudinal association fiber system, which lays connections between the frontal lobe and other areas of the ipsilateral hemisphere. As a dominant association fiber bundle, it should correspond to a well-defined structure with a clear anatomical definition. However, this is not the case, and a lot of confusion and overlap surrounds this entity. In this review/opinion study, we survey relevant current literature on the topic and try to clarify the definition of SLF in each hemisphere. After a comparison of postmortem dissections and data obtained from diffusion MRI studies, we discuss the specifics of this bundle regarding its anatomical landmarks, differences in lateralization, as well as individual variability. We also discuss the confusion regarding the arcuate fasciculus in relation to the SLF. Finally, we recommend a nomenclature based on the findings exposed in this review and finalize with a discussion on relevant functional correlates of the structure.
... These findings suggest that the co-occurrence of grey matter variations of these brain regions (lingual gyrus and lateral occipital cortex) and atypical white matter microstructure integrity of inferior longitudinal fasciculus (ILF) and inferior fronto-occipital fasciculus (IFOF) may underlie the sensory atypicalities in individuals with higher autistic traits (Itahashi et al., 2015). In addition, the white matter microstructure variations in the superior longitudinal fasciculus (SLF) (connected to the pars triangularis and Wernicke's area) may impose difficulties in acquiring language skills may be associated with autistic symptoms (Fitzgerald et al., 2018). Future studies should test these speculations by combining behavioural phenotyping and structural neuroimaging, ideally in longitudinal cohorts. ...
Autism Spectrum Disorders (ASD) are a set of neurodevelopmental conditions characterised by difficulties in social interaction and communication as well as stereotyped and restricted patterns of interest. Autistic traits exist in a continuum across the general population, whilst the extreme end of this distribution is diagnosed as clinical ASD. While many studies have investigated brain structure in autism using a case-control design, few have used a dimensional approach. To add to this growing body of literature, we investigated the structural brain correlates of autistic traits in a mixed sample of adult participants (25 ASD and 66 neurotypicals; age:18-60 years). We examined the relationship between regional brain volumes (using voxel-based morphometry and surface-based morphometry) and white matter microstructure properties (using Diffusion Tensor Imaging) and autistic traits (using Autism Spectrum Quotient). Our findings show grey matter differences in regions including the orbitofrontal cortex and lingual gyrus, and suggestive evidence for white matter microstructure differences in tracts including the superior longitudinal fasciculus being related to higher autistic traits. These grey matter and white matter microstructure findings from our study are consistent with previous reports and support the brain structural differences in ASD. These findings provide further support for shared aetiology for autistic traits across the diagnostic divide.
... Attention processing has been associated with frontal and parietal regions. The bilateral superior longitudinal fasciculus (SLF) connects the frontal regions with the parietal regions, and it consists of three frontoparietal longitudinal pathways (29)(30)(31). The SLF I is the most dorsal pathway and connects the precuneus and superior parietal lobule to the superior frontal lobes. ...
Prolactinomas have been reported for the failure of cognitive functions. However, the electrophysiological mechanisms of attention processing in prolactinomas remain unclear. In a visual mission, we monitored the scalp electroencephalography (EEG) of the participants. Compared with the healthy controls (HCs), larger frontoparietal theta and alpha coherence were found in the patients, especially in the right-lateralized hemisphere, which indicated a deficit in attention processing. Moreover, the frontoparietal coherence was positively correlated with altered prolactin (PRL) levels, implying the significance of PRL for adaptive brain compensation in prolactinomas. Taken together, this research showed the variations in attention processing between the HCs and prolactinomas. The coherence between frontal and parietal regions may be one of the possible electrophysiological biomarkers for detecting deficient attention processing in prolactinomas.
