Major White Matter Tracts Research Articles

An SBM and TBSS Analysis in Early-stage Patients With Alzheimer's Disease, Lewy Body Dementias, and Corticobasal Syndrome.

To compare gray matter (GM) and white matter (WM) changes in patients with Alzheimer's disease (AD), Lewy body dementias (LBD), corticobasal syndrome (CBS), and healthy controls (HC). Surface-based morphometry (SBM) was assessed on 3D T1-weighted images using FreeSurfer image analysis and WM microstructure was studied using Tract-Based Spatial Statistics (TBSS) in 12 AD, 15 LBD, 10 CBS patients, and 10 HC. Patients with AD, compared with HC, exhibited reduced cortical surface area and volume in the superior frontal, middle frontal, and medial orbitofrontal cortex. In TBSS, AD patients, compared with HC and LBD, displayed decreased fractional anisotropy, axial diffusivity, and increased radial diffusivity in all major WM tracts. Other comparisons between the groups yielded no differences, either in the SBM or the TBSS analysis. The results indicate significant early structural changes in the GM of the frontal lobe, along with WM alterations early in AD patients.

Lesion and lesion network localization of dysnomia after epilepsy surgery.

Temporal lobe (TL) epilepsy surgery is an effective treatment option for patients with drug-resistant epilepsy. However, neurosurgery poses a risk for cognitive deficits - up to one third of patients have a decline in naming ability following TL surgery. In this study, we aimed to better understand the neural correlates associated with reduced naming performance after TL surgery, with the goal of informing surgical planning strategies to mitigate the risk of dysnomia. We retrospectively identified 85 patients who underwent temporal lobe (TL) resective surgery (49 left TL, 36 right TL) for whom naming ability was assessed before and >3 months post-surgery using the Boston Naming Test (BNT). We used multivariate lesion-symptom mapping to identify resection sites associated with naming decline, and we used lesion-network mapping to evaluate the broader functional and structural connectivity profiles of resection sites associated with naming decline. We validated our findings in an independent cohort of 59 individuals with left temporal lobectomy, along with repeating all analyses after combining the cohorts. Lesion laterality and location were important predictors of post-surgical naming performance. Naming performance significantly improved after right temporal lobectomy (P = 0.015) while a decrement in performance was observed following left temporal lobectomy (P = 0.002). Declines in naming performance were associated with surgical resection of the left anterior middle temporal gyrus (Brodmann area 21, r =0.41, P = <.001), along with a previously implicated basal temporal language area. Resection sites linked to naming decline showed a functional connectivity profile featuring a left-lateralized network closely resembling the extended semantic \ default mode network, and a structural connectivity profile featuring major temporo-frontal association white matter tracts coursing through the temporal stem. This extends prior work by implicating the left anterior middle temporal gyrus in naming decline and provides additional support for the role of the previously identified basal temporal language area in naming decline. Importantly, the structural and functional connectivity profiles of these regions suggest they are key nodes of a broader extended semantic network. Together these regional and network findings may help in surgical planning and discussions of prognosis.

Investigating the role of structural connectivity in the individuals with moderate hearing loss

Hearing loss has been identified as a risk factor for cognitive decline. The processing of auditory information relies on a well-connected neuronal network. Previous studies have found white matter abnormalities in individuals with hearing loss, but the structural connectivity and microstructural properties of white matter in individuals with moderate hearing loss remain unclear.To examine the integrity of white matter, identify vulnerable structural connectivity, and assess network topology, we examined major white matter tracts in elderly individuals with moderate hearing loss (MHL) (>30 dB) and compared them to age-matched controls with good hearing (GH).We observed that the fractional anisotropy of the right corticospinal tract and left superior longitudinal fasciculus – parietal was higher in subjects with MHL. Additionally, we identified a disrupted network centered on the left putamen in MHL, involving eight brain regions. Network topology analysis showed reduced betweenness centrality and small-world network in MHL. Interestingly, the fractional anisotropy of the forceps major tract and left uncinate tracts were correlated with hearing status.Our findings suggest that MHL is associated with putamen-centered disruptions in structural connectivity. The increased fractional anisotropy of the right corticospinal tract may be a compensatory mechanism, as it projects fibers to the right putamen. Overall, these results provide valuable insights into the impact of hearing loss on white matter integrity and may inform the development of new treatments to prevent its progression.

Transcriptomic changes in oligodendrocyte lineage cells during the juvenile to adult transition in the mouse corpus callosum.

The corpus callosum, a major white matter tract in the brain, undergoes age-related functional changes. To extend our investigation of age-related gene expression dynamics in the mouse corpus callosum, we compared RNA-seq data from 2week-old and 12week-old wild-type C57BL/6J mice and identified the differentially expressed genes (e.g., Marcksl1, Chst3, C4b, Neat1, Ndrg1, Emid1, etc.) between these ages. Interestingly, we found that genes highly expressed in myelinating oligodendrocytes were upregulated in 12week-old mice compared to 2week-old mice, while genes highly expressed in oligodendrocyte precursor cells (OPCs) and newly formed oligodendrocytes were downregulated. Furthermore, by comparing these genes with the datasets from 20week-old and 96week-old mice, we identified novel sets of genes with age-dependent variations in the corpus callosum. These gene expression changes potentially affect key biological pathways and may be closely linked to age-related neurological disorders, including dementia and stroke. Therefore, our results provide an additional dataset to explore age-dependent gene expression dynamics of oligodendrocyte lineage cells in the corpus callosum.

Distributed associations among white matter hyperintensities and structural brain networks with fluid cognition in healthy aging

White matter hyperintensities (WMHs) are associated with age-related cognitive impairment and increased risk of Alzheimer’s disease. However, the manner by which WMHs contribute to cognitive impairment is unclear. Using a combination of predictive modeling and network neuroscience, we investigated the relationship between structural white matter connectivity and age, fluid cognition, and WMHs in 68 healthy adults (18–78 years). Consistent with previous work, WMHs were increased in older adults and exhibited a strong negative association with fluid cognition. Extending previous work, using predictive modeling, we demonstrated that age, WMHs, and fluid cognition were jointly associated with widespread alterations in structural connectivity. Subcortical-cortical connections between the thalamus/basal ganglia and frontal and parietal regions of the default mode and frontoparietal networks were most prominent. At the network level, both age and WMHs were negatively associated with network density and communicability, and positively associated with modularity. Spatially, WMHs were most prominent in arterial zones served by the middle cerebral artery and associated lenticulostriate branches that supply subcortical regions. Finally, WMHs overlapped with all major white matter tracts, most prominently in tracts that facilitate subcortical-cortical communication and are implicated in fluid cognition, including the anterior thalamic-radiations and forceps minor. Finally, results of mediation analyses suggest that whole-brain WMH load influences age-related decline in fluid cognition. Thus, across multiple levels of analysis, we showed that WMHs were increased in older adults and associated with altered structural white matter connectivity and network topology involving subcortical-cortical pathways critical for fluid cognition.

Prenatal tobacco and alcohol exposure, white matter microstructure, and early language skills in toddlers from a South African birth cohort.

Tobacco and alcohol are the two most common substances used during pregnancy, and both can disrupt neurodevelopment, resulting in cognitive and behavioral deficits including language difficulties. Previous studies show that children with prenatal substance exposure exhibit microstructural alterations in major white matter pathways, though few studies have investigated the impact of prenatal substance exposure on white matter microstructure and language skills during the toddler years. In this study, 93 children (34 exposed to alcohol and/or tobacco) aged 23 years from the Drakenstein Child Health Study, South Africa, completed Expressive and Receptive Communication assessments from the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and underwent diffusion MRI scans. Diffusion images were preprocessed, and 11 major white matter tracts were isolated. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted for each white matter tract. Linear regression was used to examine differences between the tobacco/alcohol exposed group and unexposed controls for FA, MD, and language scores, as well as relationships between brain metrics and language. There were no significant group differences in language scores or FA. Children with alcohol or tobacco exposure had lower average MD in the splenium of the corpus callosum compared to unexposed controls. Significant interactions between prenatal substance exposure and language scores were seen in 7 tracts but did not survive multiple comparisons correction. Our findings show that prenatal alcohol and/or tobacco exposure appear to alter the relationship between white matter microstructure and early language skills in this population of toddlers, potentially laying the basis of language deficits observed later in older children with prenatal substance exposure, which may have implications for learning and interventions.

Atlas-based assessment of hypomyelination: Quantitative MRI in Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is a rare childhood hypomyelinating leukodystrophy. Quantification of the pronounced myelin deficit and delineation of subtle myelination processes are of high clinical interest. Quantitative magnetic resonance imaging (qMRI) techniques can provide in vivo insights into myelination status, its spatial distribution, and dynamics during brain maturation. They may serve as potential biomarkers to assess the efficacy of myelin-modulating therapies. However, registration techniques for image quantification and statistical comparison of affected pediatric brains, especially those of low or deviant image tissue contrast, with healthy controls are not yet established. This study aimed first to develop and compare postprocessing pipelines for atlas-based quantification of qMRI data in pediatric patients with PMD and evaluate their registration accuracy. Second, to apply an optimized pipeline to investigate spatial myelin deficiency using myelin water imaging (MWI) data from patients with PMD and healthy controls. This retrospective single-center study included five patients with PMD (mean age, 6 years ± 3.8) who underwent conventional brain MRI and diffusion tensor imaging (DTI), with MWI data available for a subset of patients. Three methods of registering PMD images to a pediatric template were investigated. These were based on (a) T1-weighted (T1w) images, (b) fractional anisotropy (FA) maps, and (c) a combination of T1w, T2-weighted, and FA images in a multimodal approach. Registration accuracy was determined by visual inspection and calculated using the structural similarity index method (SSIM). SSIM values for the registration approaches were compared using a t test. Myelin water fraction (MWF) was quantified from MWI data as an assessment of relative myelination. Mean MWF was obtained from two PMDs (mean age, 3.1 years ± 0.3) within four major white matter (WM) pathways of a pediatric atlas and compared to seven healthy controls (mean age, 3 years ± 0.2) using a Mann-Whitney U test. Our results show that visual registration accuracy estimation and computed SSIM were highest for FA-based registration, followed by multimodal, and T1w-based registration (SSIMFA = 0.67 ± 0.04 vs. SSIMmultimodal = 0.60 ± 0.03 vs. SSIMT1 = 0.40 ± 0.14). Mean MWF of patients with PMD within the WM pathways was significantly lower than in healthy controls MWFPMD = 0.0267 ± 0.021 vs. MWFcontrols = 0.1299 ± 0.039. Specifically, MWF was measurable in brain structures known to be myelinated at birth (brainstem) or postnatally (projection fibers) but was scarcely detectable in other brain regions (commissural and association fibers). Taken together, our results indicate that registration accuracy was highest with an FA-based registration pipeline, providing an alternative to conventional T1w-based registration approaches in the case of hypomyelinating leukodystrophies missing normative intrinsic tissue contrasts. The applied atlas-based analysis of MWF data revealed that the extent of spatial myelin deficiency in patients with PMD was most pronounced in commissural and association and to a lesser degree in brainstem and projection pathways.

Diffusion tensor imaging in Behcet's disease with and without neurological involvement patients: evaluation of microstructural white matter abnormality with a tract-based spatial statistical analysis.

This study aims to assess the microstructural abnormalities in white matter (WM) among Behcet's disease (BD) patients, both with and without neurological involvement, utilising tract-based spatial statistics (TBSS) to elucidate the underlying causes of WM microstructural changes. This prospective study comprised 43 BD patients without neurological involvement, 15 neuro-Behcet's disease (NBD) patients with normal conventional MRI, and 54 healthy controls matched for age and sex. TBSS was applied in this diffusion tensor imaging study to conduct a whole-brain voxel-wise analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of WM. Compared to the control group, BD patients exhibited decreased FA and increased MD and RD in nearly all WM tracts, along with increased AD in the left corticospinal tract (CST), left inferior longitudinal fasciculus (ILF), and left superior longitudinal fasciculus (SLF). NBD patients also showed a widespread decrease in FA and increased MD and RD, similar to BD patients without neurological involvement. Additionally, NBD patients had increased AD in the left CST, left ILF, left SLF, left inferior fronto-occipital fasciculus (IFOF), and right CST. Compared to BD patients without neurological involvement, NBD patients exhibited a greater reduction in FA and an increase in MD and RD in WM tracts, with no significant differences in AD. These results suggest that the main mechanism of microstructural changes in the WM of BD patients may be related to impaired fibre integrity, demyelination, and decreased myelin sheath integrity. This study demonstrated BD patients without neurological involvement and NBD patients a decrease in FA and an increase in MD and RD were observed in larger areas of major WM tracts, while an increase in AD values was observed in fewer tracts. Our findings may be useful in understanding the pathophysiology underlying subclinical parenchymal involvement and neurological dysfunction in BD patients and the management of BD patients.

Impact of pathogenic variants of the Ras-mitogen-activated protein kinase pathway on major white matter tracts in the human brain.

Noonan syndrome and neurofibromatosis type 1 are genetic conditions linked to pathogenic variants in genes of the Ras-mitogen-activated protein kinase signalling pathway. Both conditions hyper-activate signalling of the Ras-mitogen-activated protein kinase pathway and exhibit a high prevalence of neuropsychiatric disorders. Further, animal models of Noonan syndrome and neurofibromatosis type 1 and human imaging studies show white matter abnormalities in both conditions. While these findings suggest Ras-mitogen-activated protein kinas pathway hyper-activation effects on white matter, it is unknown whether these effects are syndrome-specific or pathway-specific. To characterize the effect of Noonan syndrome and neurofibromatosis type 1 on human white matter's microstructural integrity and discern potential syndrome-specific influences on microstructural integrity of individual tracts, we collected diffusion-weighted imaging data from children with Noonan syndrome (n = 24), neurofibromatosis type 1 (n = 28) and age- and sex-matched controls (n = 31). We contrasted the clinical groups (Noonan syndrome or neurofibromatosis type 1) and controls using voxel-wise, tract-based and along-tract analyses. Outcomes included voxel-wise, tract-based and along-tract fractional anisotropy, axial diffusivity, radial diffusivity and mean diffusivity. Noonan syndrome and neurofibromatosis type 1 showed similar patterns of reduced fractional anisotropy and increased axial diffusivity, radial diffusivity, and mean diffusivity on white matter relative to controls and different spatial patterns. Noonan syndrome presented a more extensive spatial effect than neurofibromatosis type 1 on white matter integrity as measured by fractional anisotropy. Tract-based analysis also demonstrated differences in effect magnitude with overall lower fractional anisotropy in Noonan syndrome compared to neurofibromatosis type 1 (d = 0.4). At the tract level, Noonan syndrome-specific effects on fractional anisotropy were detected in association tracts (superior longitudinal, uncinate and arcuate fasciculi; P < 0.012), and neurofibromatosis type 1-specific effects were detected in the corpus callosum (P < 0.037) compared to controls. Results from along-tract analyses aligned with results from tract-based analyses and indicated that effects are pervasive along the affected tracts. In conclusion, we find that pathogenic variants in the Ras-mitogen-activated protein kinase pathway are associated with white matter abnormalities as measured by diffusion in the developing brain. Overall, Noonan syndrome and neurofibromatosis type 1 show common effects on fractional anisotropy and diffusion scalars, as well as specific unique effects, namely, on temporoparietal-frontal tracts (intra-hemispheric) in Noonan syndrome and on the corpus callosum (inter-hemispheric) in neurofibromatosis type 1. The observed specific effects not only confirm prior observations from independent cohorts of Noonan syndrome and neurofibromatosis type 1 but also inform on syndrome-specific susceptibility of individual tracts. Thus, these findings suggest potential targets for precise, brain-focused outcome measures for existing medications, such as MEK inhibitors, that act on the Ras-mitogen-activated protein kinase pathway.

Diffusion indices alteration in major white matter tracts of children with tic disorder using TRACULA

BackgroundTic disorder is a neuropsychiatric disorder characterized by involuntary movements or vocalizations. Previous studies utilizing diffusion-weighted imaging to explore white-matter alterations in tic disorders have reported inconsistent results regarding the affected tracts. We aimed to address this gap by employing a novel tractography technique for more detailed analysis.MethodsWe analyzed MRI data from 23 children with tic disorders and 23 healthy controls using TRActs Constrained by UnderLying Anatomy (TRACULA), an advanced automated probabilistic tractography method. We examined fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity, and mean diffusivity in 42 specific significant white matter tracts.ResultsOur findings revealed notable differences in the children with tic disorders compared to the control group. Specifically, there was a significant reduction in FA in the parietal part and splenium of the corpus callosum and the left corticospinal tract. Increased RD was observed in the temporal and splenium areas of the corpus callosum, the left corticospinal tract, and the left acoustic radiation. A higher mean diffusivity was also noted in the left middle longitudinal fasciculus. A significant correlation emerged between the severity of motor symptoms, measured by the Yale Global Tic Severity Scale, and FA in the parietal part of the corpus callosum, as well as RD in the left acoustic radiation.ConclusionThese results indicate a pattern of reduced interhemispheric connectivity in the corpus callosum, aligning with previous studies and novel findings in the diffusion indices changes in the left corticospinal tract, left acoustic radiation, and left middle longitudinal fasciculus. Tic disorders might involve structural abnormalities in key white matter tracts, offering new insights into their pathogenesis.

Anatomically constrained tractography of the fetal brain

Diffusion-weighted Magnetic Resonance Imaging (dMRI) is increasingly used to study the fetal brain in utero. An important computation enabled by dMRI is streamline tractography, which has unique applications such as tract-specific analysis of the brain white matter and structural connectivity assessment. However, due to the low fetal dMRI data quality and the challenging nature of tractography, existing methods tend to produce highly inaccurate results. They generate many false streamlines while failing to reconstruct the streamlines that constitute the major white matter tracts. In this paper, we advocate for anatomically constrained tractography based on an accurate segmentation of the fetal brain tissue directly in the dMRI space. We develop a deep learning method to compute the segmentation automatically. Experiments on independent test data show that this method can accurately segment the fetal brain tissue and drastically improve the tractography results. It enables the reconstruction of highly curved tracts such as optic radiations. Importantly, our method infers the tissue segmentation and streamline propagation direction from a diffusion tensor fit to the dMRI data, making it applicable to routine fetal dMRI scans. The proposed method can facilitate the study of fetal brain white matter tracts with dMRI.

White matter fiber morphology in persisting postconcussive symptoms and posttraumatic headache after pediatric concussion: a fixel-based analysis.

Posttraumatic headache (PTH) represents the most common acute and persistent postconcussive symptom (PCS) in children after concussion, yet there remains a lack of valid and objective biomarkers to facilitate risk stratification and early intervention in this patient population. Fixel-based analysis of diffusion-weighted imaging, which overcomes constraints of traditional diffusion tensor imaging analyses, can improve the sensitivity and specificity of detecting white matter changes postconcussion. The aim of this study was to investigate whole-brain and tract-based differences in white matter morphology, including fiber density (FD) and fiber bundle cross-section (FC) area in children with PCSs and PTH at 2 weeks after concussion. This prospective longitudinal study recruited children aged 5-18 years who presented to the emergency department of a tertiary pediatric hospital with a concussion sustained within the previous 48 hours. Participants underwent diffusion-weighted MRI at 2 weeks postinjury. Whole-brain white matter statistical analysis was performed at the level of each individual fiber population within an image voxel (fixel) to compute FD, FC, and a combined metric (FD and bundle cross-section [FDC]) using connectivity-based fixel enhancement. Tract-based Bayesian analysis was performed to examine FD in 23 major white matter tracts. Comparisons of 1) recovered (n = 27) and symptomatic (n = 16) children, and those with 2) PTH (n = 13) and non-PTH (n = 30; overall mean age 12.99 ± 2.70 years, 74% male) found no fiber-specific white matter microstructural differences in FD, FC, or FDC at 2 weeks postconcussion, when adjusting for age and sex (family-wise error rate corrected p value > 0.05). Tract-based Bayesian analysis showed evidence of no effect of PTH on FD in 10 major white matter tracts, and evidence of no effect of recovery group on FD in 3 white matter tracts (Bayes factor < 1/3). Using whole-brain fixel-wise and tract-based analyses, these findings indicate that fiber-specific properties of white matter microstructure are not different between children with persisting PCSs compared with recovered children 2 weeks after concussion. These data extend the limited research on white matter fiber-specific morphology while overcoming limitations inherent to traditional diffusion models. Further validation of our findings with a large-scale cohort is warranted.

Associative white matter tracts selectively predict sensorimotor learning

Human learning varies greatly among individuals and is related to the microstructure of major white matter tracts in several learning domains, yet the impact of the existing microstructure of white matter tracts on future learning outcomes remains unclear. We employed a machine-learning model selection framework to evaluate whether existing microstructure might predict individual differences in learning a sensorimotor task, and further, if the mapping between tract microstructure and learning was selective for learning outcomes. We used diffusion tractography to measure the mean fractional anisotropy (FA) of white matter tracts in 60 adult participants who then practiced drawing a set of 40 unfamiliar symbols repeatedly using a digital writing tablet. We measured drawing learning as the slope of draw duration over the practice session and measured visual recognition learning for the symbols using an old/new 2-AFC task. Results demonstrated that tract microstructure selectively predicted learning outcomes, with left hemisphere pArc and SLF3 tracts predicting drawing learning and the left hemisphere MDLFspl predicting visual recognition learning. These results were replicated using repeat, held-out data and supported with complementary analyses. Results suggest that individual differences in the microstructure of human white matter tracts may be selectively related to future learning outcomes.

Tractometry of the Human Connectome Project: resources and insights.

The Human Connectome Project (HCP) has become a keystone dataset in human neuroscience, with a plethora of important applications in advancing brain imaging methods and an understanding of the human brain. We focused on tractometry of HCP diffusion-weighted MRI (dMRI) data. We used an open-source software library (pyAFQ; https://yeatmanlab.github.io/pyAFQ) to perform probabilistic tractography and delineate the major white matter pathways in the HCP subjects that have a complete dMRI acquisition (n = 1,041). We used diffusion kurtosis imaging (DKI) to model white matter microstructure in each voxel of the white matter, and extracted tract profiles of DKI-derived tissue properties along the length of the tracts. We explored the empirical properties of the data: first, we assessed the heritability of DKI tissue properties using the known genetic linkage of the large number of twin pairs sampled in HCP. Second, we tested the ability of tractometry to serve as the basis for predictive models of individual characteristics (e.g., age, crystallized/fluid intelligence, reading ability, etc.), compared to local connectome features. To facilitate the exploration of the dataset we created a new web-based visualization tool and use this tool to visualize the data in the HCP tractometry dataset. Finally, we used the HCP dataset as a test-bed for a new technological innovation: the TRX file-format for representation of dMRI-based streamlines. We released the processing outputs and tract profiles as a publicly available data resource through the AWS Open Data program's Open Neurodata repository. We found heritability as high as 0.9 for DKI-based metrics in some brain pathways. We also found that tractometry extracts as much useful information about individual differences as the local connectome method. We released a new web-based visualization tool for tractometry-"Tractoscope" (https://nrdg.github.io/tractoscope). We found that the TRX files require considerably less disk space-a crucial attribute for large datasets like HCP. In addition, TRX incorporates a specification for grouping streamlines, further simplifying tractometry analysis.

Characteristic BOLD signals are detectable in white matter of the spinal cord at rest and after a stimulus

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.

Cortico-limbic interactions and carotid atherosclerotic burden during chronic stress exposure.

Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings.

3D inversion recovery ultrashort echo time MRI can detect demyelination in cuprizone-treated mice.

To test the ability of inversion-recovery ultrashort echo time (IR-UTE) MRI to directly detect demyelination in mice using a standard cuprizone mouse model. Non-aqueous myelin protons have ultrashort T2s and are "invisible" with conventional MRI sequences but can be detected with UTE sequences. The IR-UTE sequence uses an adiabatic inversion-recovery preparation to suppress the long T2 water signal so that the remaining signal is from the ultrashort T2 myelin component. In this study, eight 8-week-old C57BL/6 mice were fed cuprizone (n = 4) or control chow (n = 4) for 5 weeks and then imaged by 3D IR-UTE MRI. The differences in IR-UTE signal were compared in the major white matter tracts in the brain and correlated with the Luxol Fast Blue histochemical marker of myelin. IR-UTE signal decreased in cuprizone-treated mice in white matter known to be sensitive to demyelination in this model, such as the corpus callosum, but not in white matter known to be resistant to demyelination, such as the internal capsule. These findings correlated with histochemical staining of myelin content. 3D IR-UTE MRI was sensitive to cuprizone-induced demyelination in the mouse brain, and is a promising noninvasive method for measuring brain myelin content.

Microsurgical Resection of a Pediatric Tegmentum Tumor Through the Paramedian Supracerebellar Transtentorial Approach With the Tentorial Cut Technique: 2-Dimensional Operative Video.

The brainstem contains a highly complex group of nuclei and major white matter tracts within a small volume.1 The complex nature of its anatomy creates challenges for surgery in this area, impeding the standardization of approaches. Therefore, the concept of the "safe entry zone" should be considered with caution, and the strategy for each patient should be tailored based on the relevant subunit of the brainstem and individual patient characteristics. The critical parameter to target in patients is achieving the highest possible extent of resection while preserving function.1 The paramedian supracerebellar transtentorial approach is usually suitable for midbrain lesions. This approach allows for targeting tegmental tumors through the posterolateral midbrain surface.1 It is typically performed through a paramedian suboccipital craniotomy, ideally with the patient in the semisitting position, and is now considered a standard and safe approach.2 In patients with a spontaneous atrial right-to-left shunt, lateral or semilateral positions are viable alternatives, with the semilateral preferred for intraoperative magnetic resonance imaging.1 The cerebellar hemispheric tentorial bridging veins are usually located in the surgical route, narrowing the surgical corridor.3 Sacrifice or unintended rupture of these veins can sometimes lead to unexpected serious complications. Therefore, it is essential to preserve these veins during supracerebellar approaches.3 In this study, we demonstrate the resection of a pediatric tegmentum tumor through the left-sided paramedian supracerebellar transtentorial approach. In addition, we show the tentorial cut technique used to preserve the cerebellar hemispheric tentorial bridging veins. The patient's parents consented to the procedure and to the publication of his image.

White matter tracts adjacent to the human cingulate sulcus visual area (CSv).

Human cingulate sulcus visual area (CSv) was first identified as an area that responds selectively to visual stimulation indicative of self-motion. It was later shown that the area is also sensitive to vestibular stimulation as well as to bodily motion compatible with locomotion. Understanding the anatomical connections of CSv will shed light on how CSv interacts with other parts of the brain to perform information processing related to self-motion and navigation. A previous neuroimaging study (Smith et al. 2018, Cerebral Cortex, 28, 3685-3596) used diffusion-weighted magnetic resonance imaging (dMRI) to examine the structural connectivity of CSv, and demonstrated connections between CSv and the motor and sensorimotor areas in the anterior and posterior cingulate sulcus. The present study aimed to complement this work by investigating the relationship between CSv and adjacent major white matter tracts, and to map CSv's structural connectivity onto known white matter tracts. By re-analysing the dataset from Smith et al. (2018), we identified bundles of fibres (i.e. streamlines) from the whole-brain tractography that terminate near CSv. We then assessed to which white matter tracts those streamlines may belong based on previously established anatomical prescriptions. We found that a significant number of CSv streamlines can be categorised as part of the dorsalmost branch of the superior longitudinal fasciculus (SLF I) and the cingulum. Given current thinking about the functions of these white matter tracts, our results support the proposition that CSv provides an interface between sensory and motor systems in the context of self-motion.

Predicting functional impairments with lesion-derived disconnectome mapping: Validation in stroke patients with motor deficits.

Focal structural damage to white matter tracts can result in functional deficits in stroke patients. Traditional voxel-based lesion-symptom mapping is commonly used to localize brain structures linked to neurological deficits. Emerging evidence suggests that the impact of structural focal damage may extend beyond immediate lesion sites. In this study, we present a disconnectome mapping approach based on support vector regression (SVR) to identify brain structures and white matter pathways associated with functional deficits in stroke patients. For clinical validation, we utilized imaging data from 340 stroke patients exhibiting motor deficits. A disconnectome map was initially derived from lesions for each patient. Bootstrap sampling was then employed to balance the sample size between a minority group of patients exhibiting right or left motor deficits and those without deficits. Subsequently, SVR analysis was used to identify voxels associated with motor deficits (p < .005). Our disconnectome-based analysis significantly outperformed alternative lesion-symptom approaches in identifying major white matter pathways within the corticospinal tracts associated with upper-lower limb motor deficits. Bootstrapping significantly increased the sensitivity (80%-87%) for identifying patients with motor deficits, with a minimum lesion size of 32 and 235 mm3 for the right and left motor deficit, respectively. Overall, the lesion-based methods achieved lower sensitivities compared with those based on disconnection maps. The primary contribution of our approach lies in introducing a bootstrapped disconnectome-based mapping approach to identify lesion-derived white matter disconnections associated with functional deficits, particularly efficient in handling imbalanced data.