Projection Fibers Research Articles

PBN-PVT projections modulate negative affective states in mice.

Long-lasting negative affections dampen enthusiasm for life, and dealing with negative affective states is essential for individual survival. The parabrachial nucleus (PBN) and thalamic paraventricular nucleus (PVT) are critical for modulating affective states in mice. However, the functional roles of PBN-PVT projections in modulating affective states remain elusive. Here, we show that PBN neurons send dense projection fibers to the PVT and form direct excitatory synapses with PVT neurons. Activation of the PBN-PVT pathway induces robust behaviors associated with negative affective states without affecting nociceptive behaviors. Inhibition of the PBN-PVT pathway reduces aversion-like and fear-like behaviors. Furthermore, the PVT neurons innervated by the PBN are activated by aversive stimulation, and activation of PBN-PVT projections enhances the neuronal activity of PVT neurons in response to the aversive stimulus. Consistently, activation of PVT neurons that received PBN-PVT projections induces anxiety-like behaviors. Thus, our study indicates that PBN-PVT projections modulate negative affective states in mice.

Edge Density Imaging Identifies White Matter Biomarkers of Late-Life Obesity and Cognition.

Alzheimer disease (AD) and obesity are related to disruptions in the white matter (WM) connectome. We examined the link between the WM connectome and obesity and AD through edge-density imaging/index (EDI), a tractography-based method that characterizes the anatomical embedding of tractography connections. A total of 60 participants, 30 known to convert from normal cognition or mild-cognitive impairment to AD within a minimum of 24 months of follow up, were selected from the Alzheimer disease Neuroimaging Initiative (ADNI). Diffusion-weighted MR images from the baseline scans were used to extract fractional anisotropy (FA) and EDI maps that were subsequently averaged using deterministic WM tractography based on the Desikan-Killiany atlas. Multiple linear and logistic regression analysis were used to identify the weighted sum of tract-specific FA or EDI indices that maximized correlation to body-mass-index (BMI) or conversion to AD. Participants from the Open Access Series of Imaging Studies (OASIS) were used as an independent validation for the BMI findings. The edge-density rich, periventricular, commissural and projection fibers were among the most important WM tracts linking BMI to FA as well as to EDI. WM fibers that contributed significantly to the regression model related to BMI overlapped with those that predicted conversion; specifically in the frontopontine, corticostriatal, and optic radiation pathways. These results were replicated by testing the tract-specific coefficients found using ADNI in the OASIS-4 dataset. WM mapping with EDI enables identification of an abnormal connectome implicated in both obesity and conversion to AD.

Clinical applications of brain diffusion-tensor imaging and fiber tractography

Background Diffusion-tensor imaging (DTI) and fiber tractography are relatively recent MRI techniques that have opened an entirely new noninvasive window on the white matter (WM) connectivity of the human brain. Since their introduction, they have rapidly evolved and found application in essentially every disorder involving the WM. Aim The aim of this work was to study the clinical applications of DTI and fiber tractography in various neoplastic and nonneoplastic brain lesions, as well as to demonstrate their role in preoperative mapping of WM tracts in relation to brain lesions. Patients and methods A prospective study was conducted for 2 years on 40 patients presenting to Alexandria University with variable intracranial lesions related to WM tracts who underwent DTI and fiber tractography. The study included 25 males and 15 females. The age of the patients ranged from 6 to 76 years (mean age, 40.7 years). Qualitative analysis of DTI data was performed using directionally encoded color maps and three-dimensional tractography reconstruction. Results According to visual analysis multiple projection, association and/or commissural WM fiber tracts were involved; the most common was the corticospinal tract in 25 (62.5%) cases. WM tract involvement patterns were deviated/splayed tracts in 31 (64.6%) cases, infiltrated in nine (18.8%) cases, edematous in five (10.4%) cases, and interrupted in three (6.3%) cases. Conclusion DTI and fiber tractography are valuable noninvasive techniques providing qualitative information aiding in lesion characterization, determining WM integrity, and essential in the surgical planning for patients with intrinsic brain lesions.

Spectrum of Clinical and Imaging Characteristics of 48 X-Linked Adrenoleukodystrophy Patients: Our Experience from a University Hospital.

X-linked adrenoleukodystrophy (X-ALD) occurs due to the mutation in the ABCD1-gene. Our study was to correlate the clinical, radiological, and biochemical features in a cohort of X-ALD patients. We retrospectively analyzed 48 (M: F: 47:1) biochemically confirmed cases of X-ALD, classified them as cerebral ALD (childhood, adolescent, and adult), adrenomyeloneuropathy, Addisonian only. The Magnetic Resonance Imaging (MRI) of the radiological patterns was classified based on Loes classification. The various clinical phenotypes were childhood cerebral X-ALD (58.3%), adolescent cerebral X-ALD (14.6%), adult-cerebral X-ALD (20.8%), Addisonian variant (4.2%), and adrenomyeloneuropathy (AMN) (2.1%). The imaging features were posterior white matter (Pattern-1) observed in 33 (68.75%) patients, cerebellar white matter (Pattern-4) noted in 5 subjects, anterior white matter (Pattern-2) observed in 3 patients, combined parieto-occipital and frontal white matter (Pattern-5) observed in 3 patients, isolated projection fiber (Pattern-3) observed in 1 patient. Rare features of the involvement of optic tract, anterior and lateral columns of cervicodorsal cord, bilateral central tegmental tracts, basal ganglia, and tigroid appearance were observed. This is a comprehensive clinical, biochemical, and imaging analysis with follow-up information of one of the largest series of X-ALD patients. The knowledge regarding the clinical features, typical and atypical imaging patterns is of vital importance for early diagnosis and treatment.

Orexin neuropeptides modulate the hippocampal-dependent memory through basolateral amygdala interconnections.

Orexin neuropeptides have functional roles in hippocampal-dependent memory formation via the consolidation and retrieval of passive avoidance and spatial memories. The effects of these neuropeptides have been confirmed on the induction of long-term potentiation (LTP). The orexinergic system seems to have modulatory effects by sending projection fibers to several brain parts, such as the hippocampus and amygdala. Orexin neuropeptides activate the neural circuits of the basolateral amygdala during different arousal events with various emotional loads. Therefore, this system plays a vital role in creating appropriate behavioral reactions and responses particular to the situation. This review aimed to report new progression and advances in the hippocampus function in memory by focusing on its relationship with the amygdala through the orexinergic system.

Neural correlates in the development of and recovery from dysphagia after supratentorial stroke: A prospective tractography study

BackgroundSwallowing impairment after stroke may be related to the state of the corticobulbar tract (CBT), which is the motor projection fiber responsible for deglutition, but evidence is still lacking regarding which parameter could relate to poststroke swallowing recovery as measured by videofluroscope findings. This prospective study evaluated diffusion tensor imaging (DTI) parameters among dysphagic stroke patients compared with those of nondysphagia stroke patients and age-matched healthy subjects and followed swallowing recovery in dysphagic patients as assessed with the Modified Barium Swallow Impairment Profile (MBSImP©). MethodsDiffusion tractography was performed in 69 subjects, consisting of 27 S patients with dysphagia, 18 healthy subjects and 24 S patients with no evidence of dysphagia. DTI was performed within 14 days of stroke onset. Follow-up DTI was performed in the dysphagic group at three months. The tract volume (TV) of the CBT and frontal operculum as determined by fractional anisotropy (FA) was compared among the 3 groups. Correlations of these parameters with initial dysphagia severity and swallowing parameters at baseline and 3 months postonset were assessed. ResultsAll stroke patients showed lower CBT TV on the affected and unaffected sides than those in the control group, even in those who showed no evidence of clinical dysphagia. The dysphagia group showed a greater reduction in CBT TV on the affected side (P < 0.001). Receiver operating characteristic analysis showed that cutoff values of 4.1 cm3 for TV and 0.24 for FA from the affected side could classify dysphagia with good accuracy (AUC = 0.77, 0.75, respectively) and specificity levels. FA values in the unaffected frontal operculum showed a significant correlation (rho = −0.40, P = 0.02) with swallowing outcome as observed by the total scores of MBSImP©. In addition, these values proved to be significant variables to predict swallowing outcome in multiple regression analysis (R2 = 0.6317, adjR2 = 0.5815, F = 12.58, p < 0.001, AIC = 203.65). ConclusionsEven when clinical dysphagia is not apparent, individuals with a supratentorial stroke may show reduced CBT parameters compared to healthy controls. Supratentorial stroke may manifest with dysphagia if a certain extent of CBT volume and white matter tract integrity is involved, with a greater degree of CBT injury in the affected sides determining poststroke dysphagia severity. In contrast, recovery was independent of the affected parameters, and an initial lower FA value in the unaffected frontal operculum was indicative of a poorer 3-month dysphagia outcome. DTI parameters obtained within two weeks of stroke onset may help classify those with dysphagia, predict recovery and help plain therapeutic strategies to maintain the adaptive role of the white matter tract, which is crucial in swallowing recovery.

Prevalence of white matter pathways coming into a single white matter voxel orientation: The bottleneck issue in tractography.

Characterizing and understanding the limitations of diffusion MRI fiber tractography is a prerequisite for methodological advances and innovations which will allow these techniques to accurately map the connections of the human brain. The so‐called “crossing fiber problem” has received tremendous attention and has continuously triggered the community to develop novel approaches for disentangling distinctly oriented fiber populations. Perhaps an even greater challenge occurs when multiple white matter bundles converge within a single voxel, or throughout a single brain region, and share the same parallel orientation, before diverging and continuing towards their final cortical or sub‐cortical terminations. These so‐called “bottleneck” regions contribute to the ill‐posed nature of the tractography process, and lead to both false positive and false negative estimated connections. Yet, as opposed to the extent of crossing fibers, a thorough characterization of bottleneck regions has not been performed. The aim of this study is to quantify the prevalence of bottleneck regions. To do this, we use diffusion tractography to segment known white matter bundles of the brain, and assign each bundle to voxels they pass through and to specific orientations within those voxels (i.e. fixels). We demonstrate that bottlenecks occur in greater than 50‐70% of fixels in the white matter of the human brain. We find that all projection, association, and commissural fibers contribute to, and are affected by, this phenomenon, and show that even regions traditionally considered “single fiber voxels” often contain multiple fiber populations. Together, this study shows that a majority of white matter presents bottlenecks for tractography which may lead to incorrect or erroneous estimates of brain connectivity or quantitative tractography (i.e., tractometry), and underscores the need for a paradigm shift in the process of tractography and bundle segmentation for studying the fiber pathways of the human brain.

White matter diffusion abnormalities observed in cognitively normal elderly before conversion to mild cognitive impairment

AbstractBackgroundDifferences in white matter (WM) microstructure, as measured with diffusion tensor imaging (DTI), have been observed between cognitively normal, mild cognitively impaired (MCI), and Alzheimer’s disease (AD) patient groups. With increased focus on early intervention for AD, detection of preclinical changes is paramount; however, due to difficulties in predicting future conversion, few studies have investigated WM deterioration prior to symptom onset. Using DTI data from the Vallecas project (an 8‐year longitudinal study of healthy elderly individuals), we determine if WM changes can be found in cognitively normal individuals before conversion to MCI.MethodsFrom a baseline cohort of 824 cognitively normal 70‐85 year olds, 65 individuals converted to MCI over the study duration (mean age 77.0±4.29 years, 58% female). 65 non‐converters were matched by age, sex, and years of education to act as controls. DTI scans from one year before conversion were analysed using tract‐based spatial statistics implemented in FSL. Fractional anisotropy (FA), mean diffusivity (MD), and mode of anisotropy (MO) were compared between groups using non‐parametric permutation tests. A second comparison between future converters and all 759 non‐converters (mean age 74.0±3.92 years, 65% female) was also conducted, using age, sex, and years of education as covariates.ResultsIn the unmatched comparisons, controls had higher FA in the left forceps minor (ForMin) and anterior corona radiata (CR) (p&lt;0.05), and higher MO along the corpus callosum (CC) and ForMin (p&lt;0.01). Future converters had higher FA in the left posterior CR and corticospinal tract (p&lt;0.05), higher MD in the left anterior CR (p&lt;0.05), and higher MO along the bilateral projection fibres (p&lt;0.01). In the matched comparison, only MO differences were observed, with higher MO in controls along the body of the CC (p&lt;0.05), and higher MO in future converters in the left projection fibres and the splenium of the CC (p&lt;0.01). All significant results were FWE‐corrected.ConclusionsOur results suggest that frontal commissural fibres begin to deteriorate in cognitively normal subjects destined to convert to MCI, whilst also demonstrating selective preservation of projection fibres. We also find that MO is a sensitive measure of white matter microstructural changes presaging cognitive decline, even in preclinical populations.

Cortical thinning and white matter abnormalities relate to longitudinal neuropsychiatric symptoms differentially in predementia and dementia stages

AbstractBackgroundSubjects with cognitive impairment and dementia often suffer from neuropsychiatric symptoms (NPS). Recent studies reported the association between brain structural damages and NPS. However, little is known about how domains of NPS map to region‐specific multimodal macro‐ and micro‐structural brain changes and whether the patterns vary across different cognitive stages. Importantly, most existing evidence is cross‐sectional. Here, we sought to investigate how baseline cortical thickness (CTh) and white matter (WM) microstructure influenced longitudinal progression of NPS in predementia and dementia.MethodLongitudinal neuropsychiatric inventory (NPI) total severity and subsyndrome scores (Hyperactivity, Psychosis, Affective, Apathy) over 5 years were reported in 334 memory‐clinic patients (187 cognitive impairment no dementia (CIND) and 147 dementia). All participants underwent T1‐weighted structural and diffusion MRI at baseline. A free‐water (FW) imaging method was applied to derive individual‐level WM‐FW and tissue‐compartment maps from diffusion‐MRI. The grey matter (GM) CTh was derived using Freesurfer. We examined the association of baseline WM‐FW, WM‐tissue or GM‐CTh with baseline/longitudinal NPI (total severity and sub‐syndrome) using general linear models.ResultIn CIND, higher total NPI severity was associated with widespread WM‐FW increases (fronto‐parietal projection, temporal and callosal fibres) and more focal tissue fractional‐anisotropy (FAt) reductions (fronto‐parietal/callosal fibres) cross‐sectionally (Fig‐1). Specifically, such WM‐measures were associated with affective and hyperactive sub‐syndromes, but not with psychosis and apathy. No NPI‐cortical thickness association was detected in CIND. By contrast, in dementia, GM‐CTh in frontal executive and default mode and central sensory networks, but not WM‐alteration, was related to higher total NPI severity (Fig‐2). Also, GM‐CTh was associated with apathy and psychosis, but not with affective and hyperactive sub‐syndromes.Furthermore, baseline WM‐measures were associated with longitudinal changes in total NPI severity (Fig‐3) and affective and hyperactive in CIND. By contrast, no association was found between GM‐CTh and longitudinal NPI (total and subsyndromes) in dementia.ConclusionThis study demonstrated that WM‐abnormalities, which were early marker of disease, were related to NPS in CIND, while GM‐CTh was associated with NPS in dementia. Early identification and interventions should be developed for timely management of affective and hyperactive disorders, followed up by close monitoring of the progression of cerebral structural disruptions.

The diffuse distribution of Nav1.2 on mid-axonal regions is a marker for unmyelinated fibers in the central nervous system

Unmyelinated fibers in the central nervous system are known to exist in hippocampal mossy fibers, cerebellar parallel fibers and striatal projection fibers. Previously, we and others reported diffuse distribution of Nav1.2, a voltage-gated sodium channel α-subunit encoded by the SCN2A gene, on unmyelinated striatal projection fibers. Mutations in the SCN2A gene are associated with epilepsies and autism. In this study, we investigated the distribution of Nav1.2 on the unmyelinated fibers in the corpus callosum and stria terminalis by immunohistochemistry and immunoelectron microscopy analysis, suggesting that diffuse localization of Nav1.2 on mid-axonal regions can be a useful marker for unmyelinated fibers.

Diffusion Tensor Imaging Along the Perivascular Space Index in Different Stages of Parkinson's Disease.

Background: The aim of this study was to evaluate the glymphatic system activity in patients with Parkinson’s disease (PD) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) methods.Methods: In total, 71 patients with idiopathic PD and 36 age- and sex-matched normal controls (NCs) were involved. Patients with PD were divided into early (n = 35) and late (n = 36) subgroups, based on Hoehn and Yahr (HY) stages. We calculated the diffusivity along the perivascular spaces (ALPS), as well as projection fibers and association fibers separately, to acquire the ALPS index. Enlarged perivascular spaces (EPVS) and periventricular white matter hyperintensities were also rated. Differences in ALPS index between the PD group and NCs and between two PD subgroups and NCs were compared. In addition, a multivariate logistic regression analysis was conducted to investigate the association between ALPS index and clinical variables.Results: Patients with PD revealed lower ALPS index than NCs (p = 0.010). The late PD group exhibited significantly lower ALPS index than NCs (p = 0.006). However, there were no marked differences noticed in ALPS index between NCs and early PD group and between the two PD subgroups. In the early PD group, there was a significantly positive correlation between ALPS index and Mini-Mental State Examination (MMSE) score (β = 0.021, p = 0.029) and a negative correlation between ALPS index and EPVS score (β = −0.050, p = 0.034), after controlling for multiple variables. In the late PD group, ALPS index was inversely associated with age (β = −0.012, p = 0.004).Conclusion: Impairment of the glymphatic system is involved in PD. DTI-ALPS index could be a promising biomarker of glymphatic system in PD.

Three-Dimensionally Printed Surgical Simulation Tool for Brain Mapping Training and Preoperative Planning.

Brain mapping is the most reliable intraoperative tool for identifying surrounding functional cortical and subcortical brain parenchyma. Brain mapping procedures are nuanced and require a multidisciplinary team and a well-trained neurosurgeon. Current training methodology involves real-time observation and operation, without widely available surgical simulation. To develop a patient-specific, anatomically accurate, and electrically responsive biomimetic 3D-printed model for simulating brain mapping. Imaging data were converted into a 2-piece inverse 3D-rendered polyvinyl acetate shell forming an anatomically accurate brain mold. Functional and diffusion tensor imaging data were used to guide wire placement to approximate the projection fibers from the arm and leg areas in the motor homunculus. Electrical parameters were generated, and data were collected and processed to differentiate between the 2 tracts. For validation, the relationship between the electrical signal and the distance between the probe and the tract was quantified. Neurosurgeons and trainees were interviewed to assess the validity of the model. Material testing of the brain component showed an elasticity modulus of 55 kPa (compared to 140 kPa of cadaveric brain), closely resembling the tactile feedback a live brain. The simulator's electrical properties approximated that of a live brain with a voltage-to-distance correlation coefficient of r2=0.86. Following 32 neurosurgeon interviews, ∼96% considered the model to be useful for training. The realistic neural properties of the simulator greatly improve representation of a live surgical environment. This proof-of-concept model can be further developed to contain more complicated tractography, blood and cerebrospinal fluid circulation, and more in-depth feedback mechanisms.

Gliomas are confined to a fiber tract – Concept and clinical implications

A novel classification of white fibers of the brain has been proposed based on the direction and depth of the various fiber bundles. The implications of this classification for glioma surgery are presented. Using fiber dissection techniques described by Klingler, the various association, commissural and projection fiber bundles of the brain were studied. The fibers were studied by the naked eye and with the use of magnification. The white fibers of the cerebrum were divided architecturally into five groups- four horizontal groups and one vertical group, based on three dimensional understanding of the white fibers. The four horizontal groups are the superficial, middle, deep and central groups and the vertical group included the projection fibres. The association fibers constitute the superficial, middle and deep groups. The commissural fibers form the central group. In this article, the course of the major fiber bundles of the brain is discussed. The cortical structures and subcortical networks that are involved in major human functions are presented. The implications of the proposed classification of white fibers in the surgical management of gliomas are discussed. Deciphering the cortical and subcortical anatomy of the brain is crucial to avoid neurological morbidity while performing intra-axial brain tumor surgery.

Brain age estimation at tract group level and its association with daily life measures, cardiac risk factors and genetic variants

Brain age can be estimated using different Magnetic Resonance Imaging (MRI) modalities including diffusion MRI. Recent studies demonstrated that white matter (WM) tracts that share the same function might experience similar alterations. Therefore, in this work, we sought to investigate such issue focusing on five WM bundles holding that feature that is Association, Brainstem, Commissural, Limbic and Projection fibers, respectively. For each tract group, we estimated brain age for 15,335 healthy participants from United Kingdom Biobank relying on diffusion MRI data derived endophenotypes, Bayesian ridge regression modeling and 10 fold-cross validation. Furthermore, we estimated brain age for an Ensemble model that gathers all the considered WM bundles. Association analysis was subsequently performed between the estimated brain age delta as resulting from the six models, that is for each tract group as well as for the Ensemble model, and 38 daily life style measures, 14 cardiac risk factors and cardiovascular magnetic resonance imaging features and genetic variants. The Ensemble model that used all tracts from all fiber groups (FG) performed better than other models to estimate brain age. Limbic tracts based model reached the highest accuracy with a Mean Absolute Error (MAE) of 5.08, followed by the Commissural (hbox {MAE}=5.23), Association (hbox {MAE}=5.24), and Projection (hbox {MAE}=5.28) ones. The Brainstem tracts based model was the less accurate achieving a MAE of 5.86. Accordingly, our study suggests that the Limbic tracts experience less brain aging or allows for more accurate estimates compared to other tract groups. Moreover, the results suggest that Limbic tract leads to the largest number of significant associations with daily lifestyle factors than the other tract groups. Lastly, two SNPs were significantly (p value < 5hbox {E}{-}8) associated with brain age delta in the Projection fibers. Those SNPs are mapped to HIST1H1A and SLC17A3 genes.

Ultrastructural Evidence for Oxytocin and Oxytocin Receptor at the Spinal Dorsal Horn: Mechanism of Nociception Modulation

Oxytocin is a hypothalamic neuropeptide involved in the inhibition of nociception transmission at spinal dorsal horn (SDH) level (the first station where the incoming peripheral signals is modulated). Electrophysiological, behavioral, and pharmacological data strongly support the role of this neuropeptide and its receptor (the oxytocin receptor, OTR) as a key endogenous molecule with analgesic properties. Briefly, current data showed that oxytocin release from the hypothalamus induces OTR activation at the SDH, inducing selective inhibition of the nociceptive Aδ- and C-fibers (probably peptidergic) activity, but not the activity of proprioceptive fibers (i.e. Aβ-fibers). The above inhibition could be a direct presynaptic mechanism, or a mechanism mediated by GABAergic interneurons. However, the exact anatomical localization of oxytocin and OTR remains unclear. In this context, the present study set out to analyze the role of OTRs, GABAergic cells and CGRP fibers in the SDH in rats by using electron microscopy. Ultrastructural analyses of the SDH tissue show that: (i) oxytocin and OTR are found in asymmetrical synapsis; (ii) OTR is found in GABAergic interneurons (near unmyelinated fibers), CGRPergic fibers and glial cells; (iii) whereas oxytocin is present in supraspinal descending projection fibers. These anatomical data strongly support the notion that oxytocin released at the SDH could presynaptically inhibit the nociceptive input from the peripheral primary afferent fibers. This inhibitory action could be direct or use a GABA interneuron. Furthermore, our findings that OTR is exhibited in glial tissue at the SDH requires further exploration in nociception assays.

Exploring Signatures of Neurodegeneration in Early-Onset Older-Age Bipolar Disorder and Behavioral Variant Frontotemporal Dementia.

Introduction: Older-age bipolar disorder (OABD) may involve neurocognitive decline and behavioral disturbances that could share features with the behavioral variant of frontotemporal dementia (bvFTD), making the differential diagnosis difficult in cases of suspected dementia.Objective: To compare the neuropsychological profile, brain morphometry, and structural connectivity patterns between patients diagnosed with bvFTD, patients classified as OABD with an early onset of the disease (EO-OABD), and healthy controls (HC).Methods: bvFTD patients (n = 25, age: 66 ± 7, female: 64%, disease duration: 6 ± 4 years), EO-OABD patients (n = 17, age: 65 ± 9, female: 71%, disease duration: 38 ± 8 years), and HC (n = 28, age: 62 ± 7, female: 64%) were evaluated through neuropsychological tests concerning attention, memory, executive function, praxis, and language. Brain morphometry was analyzed through surface-based morphometry (SBM), while structural brain connectivity was assessed through diffusion tensor imaging (DTI).Results: Both bvFTD and EO-OABD patients showed lower performance in neuropsychological tests of attention, verbal fluency, working memory, verbal memory, and praxis than HC. Comparisons between EO-OABD and bvFTD showed differences limited to cognitive flexibility delayed recall and intrusion errors in the memory test. SBM analysis demonstrated that several frontal, temporal, and parietal regions were altered in both bvFTD and EO-OABD compared to HC. In contrast, comparisons between bvFTD and EO-OABD evidenced differences exclusively in the right temporal pole and the left entorhinal cortex. DTI analysis showed alterations in association and projection fibers in both EO-OABD and bvFTD patients compared to HC. Commissural fibers were found to be particularly affected in EO-OABD. The middle cerebellar peduncle and the pontine crossing tract were exclusively altered in bvFTD. There were no significant differences in DTI analysis between EO-OABD and bvFTD.Discussion: EO-OABD and bvFTD may share an overlap in cognitive, brain morphometry, and structural connectivity profiles that could reflect common underlying mechanisms, even though the etiology of each disease can be different and multifactorial.

Track-Density Ratio Mapping With Fiber Types in the Cerebral Cortex Using Diffusion-Weighted MRI.

The nerve fibers are divided into three categories: projection, commissural, and association fibers. This study demonstrated a novel cortical mapping method based on these three fiber categories using MR tractography data. The MR fiber-track data were extracted using the diffusion-weighted 3T-MRI data from 19 individuals’ Human Connectome Project dataset. Anatomical MR images in each dataset were parcellated using FreeSurfer software and Brainnetome atlas. The 5 million extracted tracks per subject by MRtrix software were classified based on the basic cortical structure (cortical area in the left and right hemisphere, subcortical area), after the tracks validation procedure. The number of terminals for each categorized track per unit-sized cortical area (1 mm3) was defined as the track-density in that cortical area. Track-density ratio mapping with fiber types was achieved by mapping the density-dependent color intensity for each categorized tracks with a different primary color. The mapping results showed a highly localized, unique density ratio map determined by fiber types. Furthermore, the quantitative group data analysis based on the parcellation information revealed that the majority of nerve fibers in the brain are association fibers, particularly in temporal, inferior parietal, and occipital lobes, while the projection and commissural fibers were mainly located in the superior part of the brain. Hemispheric asymmetries in the fiber density were also observed, such as long association fiber in the Broca’s and Wernicke’s areas. We believe this new dimensional brain mapping information allows us to further understand brain anatomy, function.

Compact Kähler manifolds with no projective specialization

We show the existence of a compact Kähler manifold which does not fit in a proper flat family over an irreducible base with one projective (possibly singular) fiber. We also give a topological version of this statement. This strengthens our earlier counterexamples to the Kodaira algebraic approximation problem.

Occipital Intralobar fasciculi: a description, through tractography, of three forgotten tracts

Diffusion MRI paired with tractography has facilitated a non-invasive exploration of many association, projection, and commissural fiber tracts. However, there is still a scarcity of research studies related to intralobar association fibers. The Dejerines’ (two of the most notable neurologists of 19th century France) gave an in-depth description of the intralobar fibers of the occipital lobe. Unfortunately, their exquisite work has since been sparsely cited in the modern literature. This work gives a modern description of many of the occipital intralobar lobe fibers described by the Dejerines. We perform a virtual dissection and reconstruct the tracts using diffusion MRI tractography. The dissection is guided by the Dejerines’ treatise, Anatomie des Centres Nerveux. As an accompaniment to this article, we provided a French-to-English translation of the treatise portion concerning five intra-occipital tracts, namely: the stratum calcarinum, the stratum proprium cunei, the vertical occipital fasciculus of Wernicke, the transverse fasciculus of the cuneus and the transverse fasciculus of the lingual lobule of Vialet. It was possible to reconstruct all but one of these tracts. For completeness, the recently described sledge runner fasciculus, although not one of the Dejerines’ tracts, was identified and successfully reconstructed.

Progression of phosphorylated α‐synuclein in Macaca fuscata

Prion‐like spreading of abnormal proteins is proposed to occur in neurodegenerative diseases, and the progression of α‐synuclein (α‐syn) deposits has been reported in the brains of animal models injected with synthetic α‐syn fibrils or pathological α‐syn prepared from patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, α‐syn transmission in nonhuman primates, which are more similar to humans, has not been fully clarified. Here, we injected synthetic human α‐syn fibrils into the left striatum of a macaque monkey (Macaca fuscata). At 3 months after the injection, we examined neurodegeneration and α‐syn pathology in the brain using α‐syn epitope‐specific antibodies, antiphosphorylated α‐syn antibodies (pSyn#64 and pSer129), anti‐ubiquitin antibodies, and anti‐p62 antibodies. Immunohistochemical examination with pSyn#64, pSer129, and α‐syn epitope‐specific antibodies revealed Lewy bodies, massive α‐syn‐positive neuronal intracytoplasmic inclusions (NCIs), and neurites in the left putamen. These inclusions were also positive for ubiquitin and p62. LB509, a human‐specific α‐syn antibody targeting amino acid residues 115–122, showed limited immunoreactivity around the injection site. The left substantia nigra (SN) and the bilateral frontal cortex also contained some NCIs and neurites. The left hemisphere, including parietal/temporal cortex presented sparse α‐syn pathology, and no immunoreactivity was seen in olfactory nerves, amygdala, hippocampus, or right parietal/temporal cortex. Neuronal loss and gliosis in regions with α‐syn pathology were mild, except for the left striatum and SN. Our results indicate that abnormal α‐syn fibrils propagate throughout the brain of M. fuscata via projection, association, and commissural fibers, though the progression of α‐syn pathology is limited.