Multi‐parameter machine learning approach to the neuroanatomical basis of developmental dyslexia

Despite decades of research, the anatomical abnormalities associated with developmental dyslexia are still not fully described. Studies have focused on between‐group comparisons in which different neuroanatomical measures were generally explored in isolation, disregarding potential interactions between regions and measures. Here, for the first time a multivariate classification approach was used to investigate grey matter disruptions in children with dyslexia in a large (N = 236) multisite sample. A variety of cortical morphological features, including volumetric (volume, thickness and area) and geometric (folding index and mean curvature) measures were taken into account and generalizability of classification was assessed with both 10‐fold and leave‐one‐out cross validation (LOOCV) techniques. Classification into control vs. dyslexic subjects achieved above chance accuracy (AUC = 0.66 and ACC = 0.65 in the case of 10‐fold CV, and AUC = 0.65 and ACC = 0.64 using LOOCV) after principled feature selection. Features that discriminated between dyslexic and control children were exclusively situated in the left hemisphere including superior and middle temporal gyri, subparietal sulcus and prefrontal areas. They were related to geometric properties of the cortex, with generally higher mean curvature and a greater folding index characterizing the dyslexic group. Our results support the hypothesis that an atypical curvature pattern with extra folds in left hemispheric perisylvian regions characterizes dyslexia. Hum Brain Mapp 38:900–908, 2017. © 2016 Wiley Periodicals, Inc.     

White matter network connectivity deficits in developmental dyslexia

A number of studies have shown an abnormal connectivity of certain white matter pathways in developmental dyslexia, as well as correlations between these white matter pathways and behavioral deficits. However, whether developmental dyslexia presents broader white matter network connectivity disruption is currently unknown. The present study reconstructed white matter networks for 26 dyslexic children (11.61 ± 1.31 years) and 31 age‐matched controls (11.49 ± 1.36 years) using constrained spherical deconvolution tractography. Network‐based statistics (NBS) analysis was performed to identify network connectivity deficits in dyslexic individuals. Network topological features were measured based on graph theory to examine whether these parameters correlate with literacy skills, and whether they explain additional variance over previously established white matter connectivity abnormalities in dyslexic children. The NBS analysis identified a network connecting the left‐occipital‐temporal cortex and temporo‐parietal cortex that had decreased streamlines in dyslexic children. Four network topological parameters (clustering coefficient, local efficiency, transitivity, and global efficiency) were positively correlated with literacy skills of dyslexic children, and explained a substantial proportion of additional variance in literacy skills beyond connectivity measures of white matter pathways. This study for the first time reports a disconnection in a local subnetwork in the left hemisphere in dyslexia and shows that the global white matter network topological properties contribute to reduced literacy skills in dyslexic children.     

Effect of experimental orthodontic pain on gray and white matter functional connectivity

AimOver 90% of patients receiving orthodontic treatment experience clinically significant pain. However, little is known about the neural correlates of orthodontic pain and which has therefore been investigated in the present study of healthy subjects using an experimental paradigm.MethodsResting‐state functional magnetic resonance imaging (rsfMRI) was performed in 44 healthy subjects 24 hours after an elastic separator had been introduced between the first and the second molar on the right side of the lower jaw and in 49 age‐ and sex‐matched healthy control (HC) subjects. A K‐means clustering algorithm was used to identify functional gray matter (GM) and white matter (WM) resting‐state networks, and differences in functional connectivity (FC) of GM and WM between the group of subjects with experimental orthodontic pain and HC were analyzed.ResultsTwelve GM networks and 14 WM networks with high stability were identified. Compared with HC, subjects with orthodontic pain showed significantly increased FC between WM12, which includes posterior thalamic radiation and posterior cingulum bundle, and most GM networks. Besides, the WM12 network showed significant differences in FC with three GM‐WM loops involving the default mode network, dorsal attention network, and salience network, respectively.ConclusionsOrthodontic pain is shown to produce an alteration of FC in networks relevant to pain processing, which may be mediated by a WM network relevant to emotion perception and cognitive processing.     

Neural dissociation of visual attention span and phonological deficits in developmental dyslexia: A hub‐based white matter network analysis

It has been suggested that developmental dyslexia may have two dissociable causes—a phonological deficit and a visual attention span (VAS) deficit. Yet, neural evidence for such a dissociation is still lacking. This study adopted a data‐driven approach to white matter network analysis to explore hubs and hub‐related networks corresponding to VAS and phonological accuracy in a group of French dyslexic children aged from 9 to 14 years. A double dissociation in brain‐behavior relations was observed. Structural connectivity of the occipital‐parietal network surrounding the left superior occipital gyrus hub accounted for individual differences in dyslexic children''s VAS, but not in phonological processing accuracy. In contrast, structural connectivity of two networks: the temporal–parietal‐occipital network surrounding the left middle temporal gyrus hub and the frontal network surrounding the left medial orbital superior frontal gyrus hub, accounted for individual differences in dyslexic children''s phonological processing accuracy, but not in VAS. Our findings provide evidence in favor of distinct neural circuits corresponding to VAS and phonological deficits in developmental dyslexia. The study points to connectivity‐constrained white matter subnetwork dysfunction as a key principle for understanding individual differences of cognitive deficits in developmental dyslexia.     

Planum temporale asymmetry in developmental dyslexia: Revisiting an old question

Among the various asymmetrical structures of the human brain, the planum temporale, an anatomical region associated with a variety of auditory and language‐related processes, has received particular attention. While its surface area has been shown to be greater in the left hemisphere compared to the right in about two‐thirds of the general population, altered patterns of asymmetry were revealed by post mortem analyses in individuals with developmental dyslexia. These findings have been inconsistently replicated in magnetic resonance imaging studies of this disorder. In this report, we attempt to resolve past inconsistencies by analyzing the T1‐weighted MR images of 81 children (mean age: 11 years, sd: 17 months), including 46 control (25 boys) and 35 dyslexic children (20 boys). We manually outlined Heschl's gyri, the planum temporale and the posterior rami of the Sylvian fissure on participants' brain images, using the same anatomical criteria as in post mortem studies. Results revealed an altered pattern of asymmetry of the planum temporale surface area in dyslexic boys only, with a greater proportion of rightward asymmetrical cases among dyslexic boys compared to control boys. Additionally, analyses of cortical thickness showed no asymmetry differences between groups for any of the regions of interest. Finally, a greater number of Heschl's gyrus full duplications emerged for the right hemisphere of dyslexic boys compared to controls. The present findings confirm and extend early post mortem observations. They also stress the importance of taking gender into account in studies of developmental dyslexia. Hum Brain Mapp 35:5717–5735, 2014. © 2014 Wiley Periodicals, Inc.     

Ischemic white matter damage and cognitive impairment

White matter damage may play an important role in the pathogenesis of vascular dementia. White matter abnormalities are easily visualized as white matter high‐intensity lesions (WML) on T2‐weighted magnetic resonance images. The extent of WML may be an indicator of cognitive impairment, in particular, impairment related to frontal lobe dysfunction. However, it is unclear whether the extent of WML is an independent predictor of cognitive impairment. In patients with extensive WML, atrophy of the corpus callosum may be an important predictor of global cognitive impairment. We investigated the relationship between the extent of WML and callosal size with cognitive function in patients who had been diagnosed with lacunar stroke or no specific neurological disease. Multivariate analysis showed that only callosal size and age were significant independent predictors of mini‐mental state examination scores (a measure of global cognitive function), whereas only the extent of WML was an independent predictor of the score on the verbal fluency task (a measure of frontal lobe function). Callosal atrophy may be an important predictor of global cognitive impairment in patients with WML, whereas the extent of WML per se may be related to impairment of frontal lobe function independent of callosal atrophy. White matter high‐intensity lesions with callosal atrophy may indicate a severe form of white matter damage with axonal loss, the degree of which may determine the severity of global cognitive impairment. Our longitudinal study revealed an association between progression of WML and vascular risk factor status during follow up in patients with initially mild WML. Early detection of WML without callosal atrophy at a stage of subtle cognitive impairment and slowing the progression of WML to a severe form with callosal atrophy might prevent the development of dementia.     

Regional and network properties of white matter function in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder with dysfunction in cortices as well as white matter (WM) tracts. While the changes to WM structure have been extensively investigated in PD, the nature of the functional changes to WM remains unknown. In this study, the regional activity and functional connectivity of WM were compared between PD patients (n = 57) and matched healthy controls (n = 52), based on multimodel magnetic resonance imaging data sets. By tract‐based spatial statistical analyses of regional activity, patients showed decreased structural‐functional coupling in the left corticospinal tract compared to controls. This tract also displayed abnormally increased functional connectivity within the left post‐central gyrus and left putamen in PD patients. At the network level, the WM functional network showed small‐worldness in both controls and PD patients, yet it was abnormally increased in the latter group. Based on the features of the WM functional connectome, previously un‐evaluated individuals could be classified with fair accuracy (73%) and area under the curve of the receiver operating characteristics (75%). These neuroimaging findings provide direct evidence for WM functional changes in PD, which is crucial to understand the functional role of fiber tracts in the pathology of neural circuits.     

2～3岁广泛性发育障碍儿童脑体积的对照研究

目的:对比分析2～3岁广泛性发育障碍儿童的脑体积异常。方法:对50例广泛性发育障碍儿童(病例组)和36名年龄、性别、智商与之相匹配的发育障碍儿童(对照组)进行T1加权三维磁共振成像扫描,应用基于体素的形态测量法比较两组全脑和脑灰、白质体积的差异。结果:与对照组相比,2～3岁广泛性发育障碍儿童全脑及脑灰、白质体积显著增大(P<0.05);左侧颞中回及颞上回灰质体积显著增大;右侧中央前回、左侧中央后回灰质体积显著减小;额中回、左侧额上回、左侧颞中回、右侧额中回及右侧颞横回处脑白质体积显著增大(P<0.001)。结论:2～3岁广泛性发育障碍儿童可能存在多个脑区体积异常改变。     

White matter connectivity damage secondary to hippocampal and amygdala target injuries in acute limbic encephalitis Diffusion tensor image and voxel-based morphometry paired study

BACKGROUND： Limbic encephalitis is a rare syndrome that specifically affects the limbic system. Magnetic resonance imaging （MRI） has been typically used to detect brain changes in this disease. However, the mechanisms of limbic encephalitis-related white matter damage remain poorly understood. OBJECTIVE： To characterize white matter connectivity changes secondary to injuries of the limbic system in limbic encephalitis through combined application of diffusion tensor imaging （DTI） and voxel-based morphometry. DESIGN, TIME AND SETTING： A non-randomized, controlled, clinical, neuroimaging, DTI study was performed at the Department of Radiology, West China Hospital in December 2008. PARTICIPANTS： A male, 46-year-old, limbic encephalitis patient, as well as 11 age- and gender-matched healthy volunteers, were enrolled in the present study. METHODS： MRI was performed on the limbic encephalitis patient using a 3.0T MR scanner. Three-dimensional SPGR Tl-weighted images and DTI were acquired in the patient and controls. Data were analyzed using Matlab 7.0 and SPM2 software. MAIN OUTCOME MEASURES： Results from routine MRI scan with contrast enhancement of patient, as well as fractional anisotropy and mean diffusivity value map differences between patient and controls. RESULTS： Significant symmetric MRI signal intensity abnormalities were observed with routine MRI Affected bilateral hippocampi and amygdala exhibited hypointense signals in TIWI and hyperintense signals in T2 images. The DTI study revealed decreased fractional anisotropy values in the bilateral alveus and fimbria of the hippocampus, bilateral internal and external capsules, white matter of the right prefrontal area, and left corona radiate in the patient compared with normal controls （P 〈 0.001） Significantly increased fractional anisotropy, mean diffusivity, or decreased mean diffusivity were not observed in the patient, compared with controls. CONCLUSION： Secondary white matter damage to the hippocampal afveus and fimbria was apparent in the limbic encephalitis patient. In addition, other white matter fiber injuries surrounded the limbic structures, which were not attributed to secondary limbic system injuries.     

Neural correlates of sequence learning in children with developmental dyslexia

Developmental Dyslexia (DD) is a condition in which reading accuracy and/or fluency falls substantially below what is expected based on the individuals age, general level of cognitive ability, and educational opportunities. The procedural circuit deficit hypothesis (PDH) proposes that DD may be largely explained in terms of alterations of the cortico‐basal ganglia procedural memory system (in particular of the striatum) whereas the (hippocampus‐dependent) declarative memory system is intact, and may serve a compensatory role in the condition. The present study was designed to test this hypothesis. Using Magnetic Resonance Imaging, we examined the functional and structural brain correlates of sequence‐specific procedural learning (SL) on the serial reaction time task, in 17 children with DD and 18 typically developing (TD) children. The study was performed over 2 days with a 24‐h interval between sessions. In line with the PDH, the DD group showed less activation of the striatum during the processing of sequential statistical regularities. These alterations predicted the amount of SL at day 2, which in turn explained variance in children''s reading fluency. Additionally, reduced hippocampal activation predicted larger SL gains between day 1 and day 2 in the TD group, but not in the DD group. At the structural level, caudate nucleus volume predicted the amount of acquired SL at day 2 in the TD group, but not in the DD group. The findings encourage further research into factors that promote learning in children with DD, including through compensatory mechanisms.     

Discriminating stress from rest based on resting‐state connectivity of the human brain: A supervised machine learning study

Acute stress induces large‐scale neural reorganization with relevance to stress‐related psychopathology. Here, we applied a novel supervised machine learning method, combining the strengths of a priori theoretical insights with a data‐driven approach, to identify which connectivity changes are most prominently associated with a state of acute stress and individual differences therein. Resting‐state functional magnetic resonance imaging scans were taken from 334 healthy participants (79 females) before and after a formal stress induction. For each individual scan, mean time‐series were extracted from 46 functional parcels of three major brain networks previously shown to be potentially sensitive to stress effects (default mode network (DMN), salience network (SN), and executive control networks). A data‐driven approach was then used to obtain discriminative spatial linear filters that classified the pre‐ and post‐stress scans. To assess potential relevance for understanding individual differences, probability of classification using the most discriminative filters was linked to individual cortisol stress responses. Our model correctly classified pre‐ versus post‐stress states with highly significant accuracy (above 75%; leave‐one‐out validation relative to chance performance). Discrimination between pre‐ and post‐stress states was mainly based on connectivity changes in regions from the SN and DMN, including the dorsal anterior cingulate cortex, amygdala, posterior cingulate cortex, and precuneus. Interestingly, the probability of classification using these connectivity changes were associated with individual cortisol increases. Our results confirm the involvement of DMN and SN using a data‐driven approach, and specifically single out key regions that might receive additional attention in future studies for their relevance also for individual differences.     

Periventricular white matter hyperintensities on MRI: correlation with neuropathologic findings.

Periventricular white matter hyperintensities on postmortem magnetic resonance imaging (MRI) and myelin-stained frontal and parietal histologic sections were evaluated independently in 12 cases. There was a strong relationship between the extent of white matter hyperintensities on MRI and the extent of gross and microscopic changes seen in the white matter of myelin-stained sections, particularly in the frontal lobe. In this material, the extent of myelin rarefaction correlated with a 0- to 8-point white matter hyperintensity scale rating on MRI in the same brains.     

Diffusion-weighted magnetic resonance imaging of white matter in bipolar disorder: a pilot study

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (MRI) has shown increased sensitivity in detecting brain white matter disease compared to traditional T2-weighted MRI. Diffusion-weighted imaging (DWI) can quantitatively assess the microstructural integrity of white matter using the average apparent diffusion coefficient (ADC(av)), a measure of the extent to which water molecules move freely within tissue. On the basis of numerous studies suggesting white matter disease in bipolar patients, particularly patients with more severe illness, this study aimed to test the utility of DWI in assessing the white matter integrity of bipolar patients with severe illness. METHODS: The existing MRI scans of eight bipolar patients and eight age-matched controls with neurological illness were examined retrospectively. ADC(av) values for pixels within white matter regions of interest (ROIs) were calculated and used to plot ADC(av) frequency histograms for each ROI. Mean ADC(av) values for the two groups were then compared by ANCOVA. RESULTS: The bipolar mean ADC(av) (0.855 +/- 0.051 x 10(-3) mm2/s) for combined white matter ROIs significantly exceeded that of controls (0.799 +/- 0.046 x 10(-3) mm2/s), while covarying for age (F = 4.47, df = 3, p = 0.025). CONCLUSIONS: This is the first report of an elevated ADC(av) in the white matter of a group of patients with bipolar disorder. In this group of patients with severe illness, increased white matter ADC(av) suggests microstructural changes consistent with decreased white matter integrity. DWI may be an additional, useful tool to assess white matter abnormalities in bipolar disorder.     

A multiparametric analysis of white matter maturation during late childhood and adolescence

White matter development has been well described using diffusion tensor imaging (DTI), but the microstructural processes driving development remain unclear due to methodological limitations. Here, using neurite orientation dispersion and density imaging (NODDI), inhomogeneous magnetization transfer (ihMT), and multicomponent driven equilibrium single‐pulse observation of T1/T2 (mcDESPOT), we describe white matter development at the microstructural level in a longitudinal cohort of healthy 6–15 year olds. We evaluated age and gender‐related trends in fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), orientation dispersion index (ODI), quantitative ihMT (qihMT), myelin volume fraction (VF_m), and g‐ratio. We found age‐related increases of VF_m in most regions, showing ongoing myelination in vivo during late childhood and adolescence for the first time. No relationship was observed between qihMT and age, suggesting myelin volume increases are driven by increased water content. Age‐related increases were observed for NDI, suggesting axonal packing is also occurring during this time. g‐ratio decreased with age in the uncinate fasciculus, implying changes in communication efficiency are ongoing in this region. FA increased and MD decreased with age in most regions. Gender effects were present in the left cingulum for FA, and an age‐by‐gender interaction was found for MD in the left uncinate fasciculus. These findings suggest that FA and MD remain useful markers of gender‐related processes, and gender differences are likely driven by factors other than myelin. We conclude that white matter development during late childhood and adolescence is driven by a combination of axonal packing and myelin volume increases.     

Reduced frontal white matter integrity in early-onset schizophrenia: a preliminary study.

BACKGROUND: Research suggests that brain frontal white matter (WM) might be qualitatively altered in adolescents with early onset schizophrenia (EOS). Diffusion tensor imaging provides a relatively new approach for quantifying possible connectivity of WM in vivo. METHODS: Diffusion tensor imaging was used to examine the WM integrity of frontal regions at seven levels from 25 mm above to 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. Three other regions were examined: the occipital region at the AC-PC plane and the genu and splenium of the corpus callosum. Fractional anisotropy was compared between 12 adolescents (nine male, 3 female) with EOS (onset of psychotic symptoms by age 18 years) and nine age-similar healthy comparison subjects (six male, 3 female). RESULTS: Adolescents with EOS had significantly reduced fractional anisotropy in the frontal WM at the AC-PC plane in both hemispheres and in the occipital WM at the AC-PC plane in the right hemisphere. CONCLUSIONS: These preliminary data support a hypothesis that alterations in brain WM integrity occur in adolescents with EOS. Abnormalities found in this study were similar to those reported in adults with chronic schizophrenia. Additional studies are needed to assess whether there is progression of WM abnormalities in schizophrenia.     

Children's reading performance is correlated with white matter structure measured by diffusion tensor imaging

We investigated the white matter structure in children (n = 14) with a wide range of reading performance levels using diffusion tensor imaging (DTI), a form of magnetic resonance imaging. White matter structure in a left temporo-parietal region that had been previously described as covarying with reading skill in adult readers also differs between children who are normal and poor readers. Specifically, the white matter structure measured using fractional anisotropy (FA) and coherence index (CI) significantly correlated with behavioral measurements of reading, spelling, and rapid naming performance. In general, lower anisotropy and lower coherence were associated with lower performance scores. Although the magnitude of the differences in children are smaller than those in adults, the results support the hypothesis that the structure of left temporoparietal neural pathways is a significant component of the neural system needed to develop fluent reading.