Middle Longitudinal Fasciculus Research Articles

Investigating white matter changes in auditory cortex and association fibres related to speech processing in noise-induced hearing loss: a diffusion tensor imaging study

BackgroundThis study explores the impact of noise-induced hearing loss (NIHL) on the microstructural integrity of white matter tracts in the brain, focusing on areas involved in speech processing. While the primary impact of hearing loss occurs in the inner ear, these changes can extend to the central auditory pathways and have broader effects on brain function. Our research aimed to uncover the neural mechanisms underlying hearing loss-related deficits in speech perception and cognition among NIHL patients.MethodsThe study included two groups: nine bilateral NIHL patients and nine individuals with normal hearing. Advanced diffusion tensor imaging techniques were employed to assess changes in the white matter tracts. Regions of interest (ROIs), including the auditory cortex, cingulum, arcuate fasciculus, and longitudinal fasciculus, were examined. Fractional anisotropy (FA) values from these ROIs were extracted for analysis.ResultsOur findings indicated significant reductions in FA values in NIHL patients, particularly in the left cingulum, right cingulum, and left inferior longitudinal fasciculus. Notably, no significant changes were observed in the auditory cortex, arcuate fasciculus, superior longitudinal fasciculus, middle longitudinal fasciculus, and right inferior longitudinal fasciculus, suggesting differential impacts of NIHL on various white matter tracts.ConclusionsThe study's findings highlight the importance of considering association fibres related to speech processing in treating NIHL, as the broader neural network beyond primary auditory structures is significantly impacted. This research contributes to understanding the neurological impact of NIHL and underscores the need for comprehensive approaches in addressing this condition.

Effect of white matter tract microstructural integrity on gamma entrainment using flickering light stimulation

AbstractBackgroundAlthough gamma entrainment using flickering light stimulation (FLS), which was found to reduce Alzheimer’s disease pathologies in mice model, it failed to reduce cerebral amyloid burden in patients with AD or mild cognitive impairment. We investigated the optimal parameters of the FLS for entraining gamma waves in older adults in their brain may be influenced by white‐matter tract microstructural integrity (WMMSI) in humans.MethodWe enrolled 31 cognitively normal volunteers aged ≥ 65 years and measured resting‐state electroencephalography and the steady‐state visually evoked potential (SSVEP) of gamma rhythms induced by optimal FLS. We analyzed the spectral power change of the electroencephalogram induced by FLS using event‐related synchronization (ERS) and the propagation of gamma rhythms from the visual cortex to other brain regions using spectral Granger causality (sGC). Diffusion tensor images were acquired, and the microstructural integrity of white‐matter tracts of interest was measured. We investigated the relationship between white matter integrity and entrainment and propagation using fractional anisotropy (FA).ResultAfter excluding five participants with SSVEP deficit, 26 participants were included in the final analysis. The lowest quartile group of the FA of the left posterior thalamic radiation exhibited a significantly lower ERS of gamma rhythms in the visual cortex than the second‐to‐highest quartile group (p = 0.045). In the multiple linear regression analyses, the effects of the FA of the middle longitudinal fasciculus and superior longitudinal fasciculus 3 on the sGC of the gamma rhythm connectivity from the occipital to the temporal, central, and frontal regions were statistically significant in both hemispheres (p < 0.05).ConclusionThese findings suggest intact WMMSI may be required for proper gamma entrainment using FLS. Therefore, future clinical trials on gamma entrainment using FLS needs to consider WMMSI for participant selection.

Localization of Silent Cerebral Infarcts in Children with Sickle Cell Disease Impacts Structural Disconnection

Silent cerebral infarcts (SCIs) occur in 40% of children with sickle cell disease (SCD) by 18 years of age and are associated with cognitive dysfunction. SCIs localize to the border zone of the brain, but the significance of this localization is unclear. In adults with stroke, an infarct's disruption of white matter (WM) tracts, or structural disconnection, is more strongly associated with the functional impact of the infarct than the size of the lesion. We aim to define the WM tracts disconnected by SCIs and the relationship between structural disconnection and functional connectivity (FC) in SCD. Simulated and real-world data were used to test the hypothesis that specific WM tracts are vulnerable to disconnection if an infarct occurs in the region at highest risk for SCIs, and that FC will decrease with increased structural disconnection in SCD. Utilizing data from the Silent Infarct Transfusion (SITT) trial, the regions at greatest risk for SCIs were defined (risk region, PMID 30061156). A simulated dataset comprised of 1000 infarcts within the risk region and 1000 infarcts within the white matter outside of the risk region was created. The real-world dataset was comprised of 44 participants with SCD and SCIs (median age 13.0 [11.0, 15.8] years, 29 female/15 male). The Human Connectome Project (HCP) 842 atlas contains thousands of streamlines comprising 28 WM tracts (excluding brainstem and cerebellar tracts). The Lesion Connectivity Toolbox defined streamlines within the HCP 842 atlas that intersected with each individual lesion, permitting quantification of two measures of structural disconnection: tract-wise disconnection (the percentage of streamlines within each tract that intersect a lesion) and global disconnection (the average percentage of streamlines connecting each pair of gray matter (GM) parcels in the FC parcellation (PMID 25316338)). Tract density images (TDi) illustrate the number of streamlines impacted by a lesion within each voxel of the brain permitting computation of total lesion impact as the volume of the TDi image associated with each lesion. Resting state functional connectivity MRI was obtained in 27 of the real-world participants for computation of whole brain modularity as a metric of global FC. The WM tracts with the highest mean tract-wise disconnection due to lesions within the risk region were the posterior and mid-anterior corpus callosum, superior longitudinal fasciculus, frontal aslant tract, and middle longitudinal fasciculus while the inferior frontal occipital fasciclus, anterior commissure, inferior longitudinal fasciculus, posterior corpus callosum, and arculate fasciculus were most impacted by lesions outside of the risk region. Numerous tracts showed a significant difference in tract-wise disconnection resulting from lesions in the risk region vs. lesions outside the risk region. The tracts impacted due to real-world lesions were similar to tracts impacted from lesions within the risk region (Table 1). Despite lesioned volume being equivalent (p = 0.31) for simulated data within and outside the risk region, the average volume of lesion impact as measured by volume of the TDi image was significantly larger for lesions occurring inside the risk region (p < 0.001; Fig 1). In the real-world dataset, whole brain modularity, a metric of global FC, decreased as global structural disconnection increased (r = -0.49, p =0.009) Using simulated data that was validated with a real-world dataset, specific WM tracts vulnerable to SCIs were identified. Previous work on cerebral hemodynamics in SCD elucidated the mechanism of injury in the border zone, and these results demonstrate the significance of the localization of this injury to the border zone. SCIs have a far-reaching effect as lesions in the risk region within the border zone were associated with a greater volume of structural disconnection compared to lesions of the same size distributed outside the risk region. These results suggest that the regions in which the SCIs localize represent “high impact” areas of the brain, where a lesion of a given volume may intersect a large number of streamlines. Further, given the correlation between global structural disconnection and whole brain modularity, these data link structural disconnection with function of the brain, suggesting these “high impact” regions may also play a key role in mediating communication between functionally connected GM regions.

Structural connectivity of cytoarchitectonically distinct human left temporal pole subregions: a diffusion MRI tractography study.

The temporal pole (TP) is considered one of the major paralimbic cortical regions, and is involved in a variety of functions such as sensory perception, emotion, semantic processing, and social cognition. Based on differences in cytoarchitecture, the TP can be further subdivided into smaller regions (dorsal, ventrolateral and ventromedial), each forming key nodes of distinct functional networks. However, the brain structural connectivity profile of TP subregions is not fully clarified. Using diffusion MRI data in a set of 31 healthy subjects, we aimed to elucidate the comprehensive structural connectivity of three cytoarchitectonically distinct TP subregions. Diffusion tensor imaging (DTI) analysis suggested that major association fiber pathways such as the inferior longitudinal, middle longitudinal, arcuate, and uncinate fasciculi provide structural connectivity to the TP. Further analysis suggested partially overlapping yet still distinct structural connectivity patterns across the TP subregions. Specifically, the dorsal subregion is strongly connected with wide areas in the parietal lobe, the ventrolateral subregion with areas including constituents of the default-semantic network, and the ventromedial subregion with limbic and paralimbic areas. Our results suggest the involvement of the TP in a set of extensive but distinct networks of cortical regions, consistent with its functional roles.

Improved prediction of glioma-related aphasia by diffusion MRI metrics, machine learning, and automated fiber bundle segmentation.

White matter impairments caused by gliomas can lead to functional disorders. In this study, we predicted aphasia in patients with gliomas infiltrating the language network using machine learning methods. We included 78 patients with left-hemispheric perisylvian gliomas. Aphasia was graded preoperatively using the Aachen aphasia test (AAT). Subsequently, we created bundle segmentations based on automatically generated tract orientation mappings using TractSeg. To prepare the input for the support vector machine (SVM), we first preselected aphasia-related fiber bundles based on the associations between relative tract volumes and AAT subtests. In addition, diffusion magnetic resonance imaging (dMRI)-based metrics [axial diffusivity (AD), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and radial diffusivity (RD)] were extracted within the fiber bundles' masks with their mean, standard deviation, kurtosis, and skewness values. Our model consisted of random forest-based feature selection followed by an SVM. The best model performance achieved 81% accuracy (specificity = 85%, sensitivity = 73%, and AUC = 85%) using dMRI-based features, demographics, tumor WHO grade, tumor location, and relative tract volumes. The most effective features resulted from the arcuate fasciculus (AF), middle longitudinal fasciculus (MLF), and inferior fronto-occipital fasciculus (IFOF). The most effective dMRI-based metrics were FA, ADC, and AD. We achieved a prediction of aphasia using dMRI-based features and demonstrated that AF, IFOF, and MLF were the most important fiber bundles for predicting aphasia in this cohort.

The Influence of Life Stress and Sleep Disturbance on White Matter Integrity.

This study investigated whether sleep and stress mutually interact to induce changes in white matter integrity. Diffusion tensor imaging (DTI) was conducted on 36 participants (male=22, female=14; mean age=38.33±12.78 years). Participants were divided into three groups depending on their sleep quality and stress levels: poor sleepers with stress, poor sleepers without stress, and good sleepers. Sleep quality and stress level were evaluated using the Pittsburgh Sleep Quality Index and the Life Experiences Survey, respectively. Fractional anisotropy (FA) values were calculated employing DTI tractography. After controlling for age and sex, poor sleepers with stress exhibited a lower FA of the left inferior cerebellar peduncle (ICP) than did poor sleepers without stress (t=2.81, p=0.02). Poor sleepers without stress showed a higher FA of the right middle longitudinal fasciculus (MdLF) than did good sleepers (t=3.35, p=0.006). The current study reports the effects of sleep, stress, and their interaction on the white matter integrities of the ICP and MdLF. ICP change seems to be associated with sleep disturbances related to stress, while MdLF change would be associated with sleep disturbances unrelated to stress.

Visual networks: Electric brain stimulation and diffusion tensor imaging

ObjectiveThe present study investigated the networks of visual functional areas using electric brain stimulation (EBS) and diffusion tensor imaging (DTI). MethodsThirteen patients with intractable focal epilepsy in which visual functional areas were identified by EBS were enrolled. An electric stimulation at 50Hz was applied to electrodes during several tasks. DTI was used to identify subcortical fibers originating from the visual functional areas identified by EBS. ResultThe electrical stimulation induced three types of visual symptoms: visual illusions (change of vision), visual hallucinations (appearance of a new object), and blurred vision. Visual illusions were associated with stimulation of lateral temporo-parieto-occipital areas, and visual hallucinations with stimulation of lateral/basal temporal areas, the occipital lobe and the precuneus. Stimulus intensities eliciting visual illusions were significantly higher than those for visual hallucinations. Tractography revealed that the superior fronto-occipital fasciculus was associated with visual illusions and the middle longitudinal fasciculus with visual hallucinations, and both symptoms shared several subcortical fibers such as the vertical occipital fasciculus, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, inferior longitudinal fasciculus, optic radiations, and commissural fibers. ConclusionThe present study revealed the characteristic cortical regions and networks of visual functional areas. The results obtained provide information on human visual functions and are a practical guide for electrical cortical stimulation.

A narrative review of the anatomy and function of the white matter tracts in language production and comprehension.

Much is known about the role of cortical areas in language processing. The shift towards network approaches in recent years has highlighted the importance of uncovering the role of white matter in connecting these areas. However, despite a large body of research, many of these tracts' functions are not well-understood. We present a comprehensive review of the empirical evidence on the role of eight major tracts that are hypothesized to be involved in language processing (inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, extreme capsule, middle longitudinal fasciculus, superior longitudinal fasciculus, arcuate fasciculus, and frontal aslant tract). For each tract, we hypothesize its role based on the function of the cortical regions it connects. We then evaluate these hypotheses with data from three sources: studies in neurotypical individuals, neuropsychological data, and intraoperative stimulation studies. Finally, we summarize the conclusions supported by the data and highlight the areas needing further investigation.

Supramarginal Gyrus and Angular Gyrus Subcortical Connections: A Microanatomical and Tractographic Study for Neurosurgeons

Background and Objectives: This article aims to investigate the subcortical microanatomy of the supramarginal gyrus (SMG) and angular gyrus (AnG) using a microfiber dissection technique and diffusion tensor imaging (DTI)/fiber tractography (FT). The cortical and subcortical structures of this region are highly functional, and their lesions often present clinically. For this reason, the possibility of post-surgical deficits is high. We focused on the supramarginal gyrus and the angular gyrus and reviewed their anatomy from a topographic, functional and surgical point of view, and aimed to raise awareness especially for neurosurgeons. Methods: Four previously frozen, formalin-fixed human brains were examined under the operating microscope using the fiber dissection technique. Four hemispheres were dissected from medial to lateral under the surgical microscope. Brain magnetic resonance imaging (MRI) of 20 healthy adults was examined. Pre-central and post-central gyrus were preserved to achieve topographic dominance in dissections of brain specimens. Each stage was photographed. Tractographic brain magnetic resonance imaging of 10 healthy adults was examined radiologically. Focusing on the supramarginal and angular gyrus, the white matter fibers passing under this region and their intersection areas were examined. These two methods were compared anatomically from the lateral view and radiologically from the sagittal view. Results: SMG and AnG were determined in brain specimens. The pre-central and post-central gyrus were topographically preserved. The superior and medial temporal gyrus, and inferior and superior parietal areas were decorticated from lateral to medial. U fibers, superior longitudinal fasciculus II (SLF II), superior longitudinal fasciculus III (SLF III), arcuat fasciculus (AF) and middle longitudinal fasciculus (MdLF) fiber groups were shown and subcortical fiber structures belonging to these regions were visualized by the DTI/FT method. The subcortical fiber groups under the SMG and the AnG were observed anatomically and radiologically to have a dense and complex structure. Conclusions: Due to the importance of the subcortical connections of SMG and AnG on speech function, tumoral lesions and surgeries of this region are of particular importance. The anatomical architecture of the complex subcortical structure, which is located on the projection of the SMG and AnG areas, was shown with a DTI/FT examination under a topographic dominance, preserving the pre-central and post-central gyrus. In this study, the importance of the anatomical localization, connections and functions of the supramarginal and angular gyrus was examined. More anatomical and radiological studies are needed to better understand this region and its connections.

Contribution of White Matter Fiber Bundle Damage to Language Change After Surgery for Temporal Lobe Epilepsy.

In medically refractory temporal lobe epilepsy (TLE), 30%-50% of patients experience substantial language decline after resection in the language-dominant hemisphere. In this study, we investigated the contribution of white matter fiber bundle damage to language change at 3 and 12 months after surgery. We studied 127 patients who underwent TLE surgery from 2010 to 2019. Neuropsychological testing included picture naming, semantic fluency, and phonemic verbal fluency, performed preoperatively and 3 and 12 months postoperatively. Outcome was assessed using reliable change index (RCI; clinically significant decline) and change across timepoints (postoperative scores minus preoperative scores). Functional MRI was used to determine language lateralization. The arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus, middle longitudinal fasciculus (MLF), and uncinate fasciculus were mapped using diffusion MRI probabilistic tractography. Resection masks, drawn comparing coregistered preoperative and postoperative T1 MRI scans, were used as exclusion regions on preoperative tractography to estimate the percentage of preoperative tracts transected in surgery. Chi-squared assessments evaluated the occurrence of RCI-determined language decline. Independent sample t tests and MM-estimator robust regressions were used to assess the impact of clinical factors and fiber transection on RCI and change outcomes, respectively. Language-dominant and language-nondominant resections were treated separately for picture naming because postoperative outcomes were significantly different between these groups. In language-dominant hemisphere resections, greater surgical damage to the AF and IFOF was related to RCI decline at 3 months. Damage to the inferior frontal subfasciculus of the IFOF was related to change at 3 months. In language-nondominant hemisphere resections, increased MLF resection was associated with RCI decline at 3 months, and damage to the anterior subfasciculus was related to change at 3 months. Language-dominant and language-nondominant resections were treated as 1 cohort for semantic and phonemic fluency because there were no significant differences in postoperative decline between these groups. Postoperative seizure freedom was associated with an absence of significant language decline 12 months after surgery for semantic fluency. We demonstrate a relationship between fiber transection and naming decline after temporal lobe resection. Individualized surgical planning to spare white matter fiber bundles could help to preserve language function after surgery.

White Matter Correlates of Domain-Specific Working Memory.

Prior evidence suggests domain-specific working memory (WM) buffers for maintaining phonological (i.e., speech sound) and semantic (i.e., meaning) information. The phonological WM buffer's proposed location is in the left supramarginal gyrus (SMG), whereas semantic WM has been related to the left inferior frontal gyrus (IFG), the middle frontal gyrus (MFG), and the angular gyrus (AG). However, less is known about the white matter correlates of phonological and semantic WM. We tested 45 individuals with left hemisphere brain damage on single word processing, phonological WM, and semantic WM tasks and obtained T1 and diffusion weighted neuroimaging. Virtual dissections were performed for each participants' arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), middle longitudinal fasciculus (MLF), and uncinate fasciculus (UF), which connect the proposed domain-specific WM buffers with perceptual or processing regions. The results showed that the left ILF, MLF, IFOF, and the direct segment of the AF were related to semantic WM performance. Phonological WM was related to both the left ILF and the MLF. This work informs our understanding of the white matter correlates of WM, especially semantic WM, which has not previously been investigated. In addition, this work helps to adjudicate between theories of verbal WM, providing some evidence for separate pathways supporting phonological and semantic WM.

WHITE MATTER CHANGE NEAR CEREBRAL MICROBLEEDS AFTER MTBI INVOLVES AGE AND SEX DEPENDENT COGNITIVE DECLINE

Abstract We tested the null hypothesis that, after mild traumatic brain injury (mTBI), white matter changes near cerebral microbleeds (CMBs) are associated with cognitive decline. Magnetic resonance images were acquired from 62 adults with mTBI and from 203 matched healthy controls. A week post-injury, mTBI participants had 2.7±2.6 traumatic CMBs in WM, located 6.1±4.4 mm from the cortical mantle. About 6 months later, 97% of CMBs were associated with significant reductions (34%±11%, q < 0.05) in the fractional anisotropy (FA) of WM streamlines within ~1 cm of CMBs. Male sex and older age were significant risk factors for larger reductions (q < 0.05). CMBs in the corpus callosum, cingulum bundle, inferior and middle longitudinal fasciculi were associated with FA changes that were significantly and positively associated with changes in cognitive functions mediated by these structures (q < 0.05). These findings distinguish non-traumatic from traumatic CMBs according to CMB-related changes in surrounding WM. Our findings also challenge the assumption that traumatic CMBs are cognitively silent and identify older age and male sex as risk factors for mTBI-related cognitive decline in the presence of CMBs. In conclusion, mTBI with CMB findings on MRI can be described as a clinical endophenotype that warrants longitudinal mapping and quantification of cognitive function.

Beyond the Dorsal Column Medial Lemniscus in Proprioception and Stroke: A White Matter Investigation.

Proprioceptive deficits are common following stroke, yet the white matter involved in proprioception is poorly understood. Evidence suggests that multiple cortical regions are involved in proprioception, each connected by major white matter tracts, namely: Superior Longitudinal Fasciculus (branches I, II and III), Arcuate Fasciculus and Middle Longitudinal Fasciculus (SLF I, SLF II, SLF III, AF and MdLF respectively). However, direct evidence on the involvement of these tracts in proprioception is lacking. Diffusion imaging was used to investigate the proprioceptive role of the SLF I, SLF II, SLF III, AF and MdLF in 26 participants with stroke, and seven control participants without stroke. Proprioception was assessed using a robotic Arm Position Matching (APM) task, performed in a Kinarm Exoskeleton robotic device. Lesions impacting each tract resulted in worse APM task performance. Lower Fractional Anisotropy (FA) was also associated with poorer APM task performance for the SLF II, III, AF and MdLF. Finally, connectivity data surrounding the cortical regions connected by each tract accurately predicted APM task impairments post-stroke. This study highlights the importance of major cortico-cortical white matter tracts, particularly the SLF III and AF, for accurate proprioception after stroke. It advances our understanding of the white matter tracts responsible for proprioception.

Microstructural diffusivity (DTI) changes underlying visual short‐term memory deficits in Alzheimer's Disease detected by digital screening

AbstractBackgroundDeficits in visual short‐term memory (STM), rather than episodic long‐term memory, have recently been found to be associated with Alzheimer’s Disease (AD). However, the brain microstructural underpinning of selective abilities within visual STM remains poorly described.Method52 AD and 60 age‐matched healthy controls were recruited from the Oxford Centre for Cognitive Disorders. We used a novel digital visual STM task – the “What was where?” task (Figure 1) and extracted four metrics: Identification Accuracy (percentage of correctly identified items), Target detection (probability of correctly identifying the target), Misbinding (erroneously localizing an item to the remembered location of another item in memory) and Guessing (random guessing), (Figure 1). We then applied TBSS (Tract‐Based Spatial Statistics) to investigate in which areas of the brain microstructural disruption of physiological diffusivity correlated with behavioural performance.ResultIn AD patients, a core area including Forceps Major, left Optic Radiation (OR) and left Middle Longitudinal Fasciculus (MLF) was commonly associated with performance across all four metrics (Figure 2). Misbinding also involved the left MLF (part III), left inferior Fronto‐Occipital Fasciculus (IFOF) and left Vertical Occipital Fasciculus (VOF). Target detection additionally was associated with Superior Longitudinal Fasciculus (SLF), and Identification Accuracy with left Superior Thalamic Radiation (STR) in AD and also right OR in controls.ConclusionThere is a common shared area of altered diffusivity in AD patients that underlies a global impairment in visual STM, while distinct types of memory errors were associated with disruption of additional contribution of selective white matter fibers.

P01.19.A The temporo-parieto-occipital junction in the non-dominant hemisphere as a challenging hub for glioma surgery: functional and oncological outcomes

Abstract Background The temporo-parieto-occipital junction (TPOJ) in the non-dominant hemisphere is a complex region intersected by multiple white matter bundles (Optic radiations, Inferior-fronto-occipital tract, inferior-longitudinalis-tract, superior-longitudinalis-tract, vertical-occipital-tract, medial-dorsal-longitudinal-tract, parietal-aslant-tract), subserving several high-level neurological functions such as spatial recognition, visual agnosia, visual field, attention and working memory. Few data are available on the optimum brain mapping strategy to be adopted for resecting tumors involving this area. Ideally it should allow surgeon to effectively identify several tracts and safely preserve all functions. Material and Methods We developed a proper protocol to approach this complex area integrating, in awake condition, intraoperative visual test (iVT) to mapping visual field, semantic association test (SRAT) to prevent visual agnosia and preserve working memory, hand manipulation task (hMT) to preserve spatial abilities. We reviewed its efficacy in a series of 38 patients with tumors involving non-dominant TPOJ, looking to functional (neurologic-neuropsychological) and oncological (EOR) outcomes. we perform a lesion symptom map and a disconnectome analysis to evaluate what region predict a decline in neuropsychological function and which tract of white brain matter are correlated in the decline of performance. Results Feasibility was high and all patients were able to perform and complete the protocol, which lasted, on the average11 min cortically and 25 min subcortically. Specificity was >95%. Immediate post-operative deficits were documented in 87.4% of patients, permanent in 3.9% (visual field, visual spatial abilities). Attentive and emotional domains were those mostly affected in the neuropsychological evaluation. Lesion symptom mapping and disconnectomic analysis showed that the postoperative decrease in neuropsychological performance was associated with resection of a cluster of voxels corresponding to the anterior portion of the temporo-parietal junction. The white matter tracts mainly involved were the anterior and posterior segment of the middle longitudinal fasciculus (aMdLF and pMdLF) and the parietal aslant tract (PAT). Conclusion Effective and safe resection of tumors involving non-dominant TPOJ is feasible. The adoption of a specific brain mapping protocol in awake setting is recommended to achieve a full functional preservation and extend tumor resection. Further analysis should be performed to assess the role of this subcortical tracts.

The connectivity-based parcellation of the angular gyrus: fiber dissection and MR tractography study.

The angular gyrus (AG) wraps the posterior end of the superior temporal sulcus (STS), so it is considered a continuation of the superior temporal gyrus (STG)/ middle temporal gyrus (MTG) and forms the inferior parietal lobule (IPL) with the supramarginal gyrus (SMG). The AG was functionally divided in the literature, but there is no fiber dissection study in this context. This study divided AG into superior (sAG) and inferior (iAG) parts by focusing on STS. Red, blue silicone-injected eight and four non-silicone-injected human cadaveric cerebrums were dissected via the Klingler method focusing on the AG. White matter (WM) tracts identified during dissection were then reconstructed on the Human Connectome Project 1065 individual template for validation. According to this study, superior longitudinal fasciculus (SLF) II and middle longitudinal fasciculus (MdLF) are associated with sAG; the anterior commissure (AC), optic radiation (OR) with iAG; the arcuate fasciculus (AF), inferior frontooccipital fasciculus (IFOF), and tapetum (Tp) with both parts. In cortical parcellation of AG based on STS, sAG and iAG were associated with different fiber tracts. Although it has been shown in previous studies that there are functionally different subunits with AG parcellation, here, for the first time, other functions of the subunits have been revealed with cadaveric dissection and tractography images.

White matter degradation near cerebral microbleeds is associated with cognitive change after mild traumatic brain injury

To explore how cerebral microbleeds (CMBs) accompanying mild traumatic brain injury (mTBI) reflect white matter (WM) degradation and cognitive decline, magnetic resonance images were acquired from 62 mTBI adults (imaged ∼7 days and ∼6 months post-injury) and 203 matched healthy controls. On average, mTBI participants had a count of 2.7 ± 2.6 traumatic CMBs in WM, located 6.1 ± 4.4 mm from cortex. At ∼6-month follow-up, 97% of CMBs were associated with significant reductions (34% ± 11%, q < 0.05) in the fractional anisotropy of WM streamlines within ∼1 cm of CMB locations. Male sex and older age were significant risk factors for larger reductions (q < 0.05). For CMBs in the corpus callosum, cingulum bundle, inferior and middle longitudinal fasciculi, fractional anisotropy changes were significantly and positively associated with changes in cognitive functions mediated by these structures (q < 0.05). Our findings distinguish traumatic from non-traumatic CMBs by virtue of surrounding WM alterations and challenge the assumption that traumatic CMBs are neurocognitively silent. Thus, mTBI with CMB findings can be described as a clinical endophenotype warranting longitudinal cognitive assessment.

Track-weighted imaging analysis of white matter microstructures in healthy children: Sex and hemispheric differences.

Structural substrates of sex differences in human function and behavior have been elucidated in previous studies. Diffusion weighted magnetic resonance imaging (DW-MRI) is a widely used non-invasive imaging technique in studying human brain white matter structural organization. While many DW-MRI studies reporting sex differences in WM structure are based on diffusion tensor imaging (DTI) measures, tract specific microstructural differences require further investigation. In this study, we aim to investigate sex differences and sex-specific hemispheric differences in white matter microstructural development in healthy 8-year-old children based on novel track weighted imaging (TWI) analysis. Average pathlength map (APM) is a TWI contrast in which the average length of fibers passing through a voxel is utilized. In this study, we employed tract specific APM measures to evaluate sex differences in WM microstructural development. A total of 37 WM tracts were analyzed including 7 commissural tracts, 9 bilateral association tracts and 6 bilateral projection tracts. APM maps were generated for each tract. Tract-wise group tests were done using the mean values of APM maps. Sex differences were tested using general linear model based group comparisons. Age and total brain volume were included as covariates in the group analysis. Sex specific hemispheric differences were performed for the 15 bilateral tracts. One sample t-tests were done independently for left>right and right>left cases and the APM measures were controlled for age and total cerebral hemispheric volume. P-values<0.05 were considered significant after correcting for multiple comparisons accounting for the total number of tracts. Significant sex differences were revealed in APM measures between boys and girls in 11 WM tracts including rostral body of corpus callosum (CC), left inferior fronto-occipital fasciculus (IFOF), right cingulum, bilateral first and second segments of superior longitudinal fasciculus (SLF), right middle longitudinal fasciculus (MLF), bilateral fronto-pontine (FPT) and right parieto-occipital pontine tracts (POPT). The sex differences showed higher APM values for these 11 tracts in boys as compared to that of girls. In hemispheric differences analysis for both boys and girls, 2 tracts, arcuate fasciculus and optic radiation showed higher APM in left tracts as compared right; 5 tracts, IFOF, MLF, third segment of SLF, FPT and superior thalamic radiation showed higher APM in right tracts as compared to left. This indicates that boys and girls possess similar lateral asymmetries in these 7 tracts. Additionally, anterior thalamic radiation (ATR) showed higher APM in left tract and 4 tracts, first segment of SLF, POPT, inferior longitudinal fasciculus and cortico-spinal tract showed higher APM in right for boys. In girls, second segment of SLF and uncinate fasciculus showed higher APM in right hemisphere. These results indicate different lateral asymmetries between boys and girls for 7 tracts. Overall, boys showed higher average fiber length in most of the tracts, even after controlling for total brain volume.

Neural correlates of sleep quality in children: Sex-specific associations shown by brain diffusion tractography.

Sleep quality is important for healthy growth and development of children. We aimed to identify associations between sleep disturbances in healthy children without clinical diagnosis of sleep disorders and brain white matter (WM) microstructure using an advanced diffusion-weighted magnetic resonance imaging (DW-MRI) based tractography analysis, and to explore whether there are sex differences in these associations. Brain DW-MRI data were collected from sixty-two 8-year-old children (28 boys, 34 girls) whose parents also completed Children's Sleep Habits Questionnaire (CSHQ). Track-weighted imaging (TWI) measures were computed from the DW-MRI data for 37 WM tracts in each subject. Sex-specific partial correlation analyses were performed to evaluate correlations between TWI measures and a set of sleep disturbance scores derived from the CSHQ. Significant correlations (P<.05, FDR-corrected; r: .48-.67) were identified in 13 WM tracts between TWI and sleep disturbance scores. Sexually dimorphic differences in correlations between sleep disturbance scores and WM microstructure measurements were observed. Specifically, in boys, daytime sleepiness positively correlated with track-weighted mean or radial diffusivity in 10 WM tracts (bilateral arcuate fasciculus, left cingulum, right middle longitudinal fasciculus, and three bilateral segments of superior longitudinal fasciculus). In girls, total CSHQ score, night walking, or sleep onset delay negatively correlated with track-weighted fractional anisotropy or axial diffusivity in 4 WM tracts (bilateral inferior longitudinal fasciculus and uncinate fasciculus). The findings suggest that sleep disturbances without clinical diagnosis of sleep disorders are associated with lower WM microstructural integrity in children. Additionally, the associations possess unique patterns in boys and girls.

Age, Sex, and Cerebral Microbleeds Affect White Matter Integrity Across Adulthood After Mild Traumatic Brain Injury

The contributions of age, sex, and cerebral microbleeds (CMBs) to WM changes after mild traumatic brain injury (mTBI) have not been studied. We used diffusion tensor imaging (DTI) to map WM fractional anisotropy (FA) changes across the first ~6 months post-mTBI in 109 subjects aged 18-77 (46 females; age µ: 40 y, σ: 17 y) imaged within ~1 week post-injury and ~6 months later. After partialing out age, sex, and CMB counts, significant mean FA decreases were found in the anterior body, posterior body, and splenium of the corpus callosum (CC; p = 0.003, 0.009 and 0.015, respectively), left superficial frontal fasciculus (p = 0.008), and left branch of the corticospinal tract (CST; p = 0.007). Age contributed to mean FAs measured acutely in the CC body (p = 0.04), and chronically in the CC genu (p < 0.001), CC body (p = 0.01), and middle longitudinal fasciculi (p = 0.04), older adults exhibiting larger decreases. CMB counts were positively associated with mean FA decreases in the CC body (p = 0.04) and middle longitudinal fasciculi (p = 0.04). Significant age-by-sex and CMB count-by-age interactions mediated FA decreases in the CC genu (p = 0.02 and p = 0.03, respectively), older males exhibiting larger decreases. Thus, the CC, longitudinal fasciculi, superficial frontal WM and CST are particularly vulnerable to post-traumatic neurodegeneration moderated by age, sex and CMB count, men and older adults being at highest risk for adverse effects. Future research should investigate our findings relative to cognitive function.