Fiber Tracts Research Articles

Microsurgical Resection of a Midbrain Cavernous Malformation via the Paramedian Supracerebellar Infratentorial Translateral Mesencephalic Sulcus Approach Using the Dynamic Lateral Semisitting Position: Two-Dimensional Operative Video with 3-Dimensional Anatomical Models.

Brainstem cavernous malformations are relatively rare lesions with a higher tendency of hemorrhage than supratentorial cavernous malformations. Due to the compact arrangement of fiber tracts and nuclei of the region, any hemorrhagic event can cause severe neurological deficits. This eloquent architecture of the area also makes any surgical attempt challenging. Anatomical location and dimension of the lesion, presence of hemorrhage, age, and the neurological status of the patient need to be considered before determining the appropriate course of treatment. A surgical approach is preferred for young symptomatic patients with at least 1 previous episode of bleeding. Subtemporal and supracerebellar infratentorial approaches can be used to access these lesions.1-5 We present a 44-year-old woman with a hemorrhagic tegmental cavernous malformation presenting with imbalance and right-sided hemiparesis (Video 1). The paramedian supracerebellar infratentorial translateral mesencephalic sulcus approach is used to resect the lesion with the patient in a dynamic lateral semisitting position. The paramedian variant of the supracerebellar infratentorial approach provides a relatively bridging vein-free corridor compared with midline approaches.6 With the patient in the semisitting position, gravity retraction of the brain provided a natural corridor with a clear surgical field. In the dynamic lateral semisitting position, we aimed to reduce the risk of venous air embolism associated with the sitting position by keeping the patient in the lateral decubitus position during the dural and extradural phases of the surgery.7.

Targeting GABA signaling in type 1 diabetes and its complications- an update on the state of the art.

Type 1 diabetes (T1D) is an autoimmune disease that leads to the progressive destruction of insulin-producing β cells, resulting in lifelong insulin dependence and a range of severe complications. Beyond conventional glycemic control, innovative therapeutic strategies are needed to address the underlying disease mechanisms. Recent research has highlighted gamma-aminobutyric acid (GABA) as a promising therapeutic target for T1D due to its dual role in modulating both β cell survival and immune response within pancreatic islets. GABA signaling supports β cell regeneration, inhibits α cell hyperactivity, and promotes α-to-β cell transdifferentiation, contributing to improved islet function. Moreover, GABA's influence extends to mitigating T1D complications, including nephropathy, neuropathy, and retinopathy, as well as regulating central nervous system pathways involved in glucose metabolism. This review consolidates the latest advances in GABA-related T1D therapies, covering animal preclinical and human clinical studies and examining the therapeutic potential of GABA receptor modulation, combination therapies, and dietary interventions. Emphasis is placed on the translational potential of GABA-based approaches to enhance β cell viability and counteract autoimmune processes in T1D. Our findings underscore the therapeutic promise of GABA signaling modulation as a novel approach for T1D treatment and encourage further investigation into this pathway's role in comprehensive diabetes management.

White Matter Fiber Bundle Alterations Correlate with Gait and Cognitive Impairments in Parkinson's Disease based on HARDI Data.

The neuroanatomical basis of white matter fiber tracts in gait impairments in individuals suffering from Parkinson's Disease (PD) is unclear. Twenty-four individuals living with PD and 29 Healthy Controls (HCs) were included. For each participant, two-shell High Angular Resolution Diffusion Imaging (HARDI) and high-resolution 3D structural images were acquired using the 3T MRI. Diffusion-weighted data preprocessing was performed using the orientation distribution function to trace the main fiber tracts in PD individuals. Clinical characteristics between the two groups were compared, and the correlation between the FA value and behavioral data was analyzed. Quantitative gait and clinical parameters were recorded in PD at ON and OFF states, respectively. The mean tract-specific FA values of the right Cingulum Cingulate (rCC) were statistically different between the PD group and the HC group (p =0.047). The FA value of 34-58 equidistant nodes in rCC was positively correlated with Mini-Mental State Examination (MMSE) (r=0.527, p=0.024), Berg Balance Scale (BBS)-OFF (r=0.480, p =0.040), and BBS-ON (r=0.528, p =0.024) scores, while it was negatively correlated with the MDS-UPDRS-III-ON score (r=-0.502, p =0.030). Regarding the gait analysis, the FA value was significantly correlated with velocity, cadence, and stride time of the pace and rhythm domains in both 'ON' and 'OFF' states, respectively (p<0.05). This study served as an initial exploration to establish that HARDI sequences could be employed as a robust tool for analyzing microstructural alterations in white matter fiber bundles among PD patients, although the sample size was small. We confirmed microstructural integrity impairment of rCC to be significantly associated with both gait and cognitive deficits in patients with PD. Early detection of microstructural changes in rCC and targeted treatment can help improve behavioral disorders. In the future, we intend to further integrate multimodal data with assessments of patient behavior both prior to and following intervention. We will validate our findings within an independent cohort to monitor disease progression and evaluate the efficacy of therapeutic interventions.

Advances in diagnostic imaging and interventional treatment of aphasia after basal ganglia stroke.

Post-stroke basal ganglia aphasia is an unusual and transient form of aphasia resulting from basal ganglia damage. It is commonly believed that the generation of language function primarily resides in regular language regions of the brain; however, recent findings indicate a prevalence of basal ganglia stroke aphasia as high as 22%. Subcortical structures (e.g., basal ganglia) also play an important role in language processing. Aphasia seriously affects the quality of life and functional outcomes of patients, and early diagnosis and intervention are important for the prognosis of and rehabilitation from aphasia after basal ganglia stroke. In recent years, the main diagnostic methods for basal ganglia aphasia include diffusion tensor imaging, diffusion spectral imaging, and functional magnetic resonance imaging, which explore the changes in patients with basal ganglia aphasia compared to those without from the perspectives of fiber tract imaging and brain function alteration, respectively, and are able to predict the recovery of patients before and after treatment. Treatment for post-stroke basal ganglia aphasia includes transcranial magnetic stimulation, a recent emerging therapeutic technique, in addition to conventional medications and speech rehabilitation. Consequently, understanding this condition is crucial. This review delves into its causes, imaging methods, and therapeutic interventions, offering a systematic and comprehensive analysis of these aspects.

Fast Neuronal Calcium Signals in Brain Slices Loaded With Fluo-4 AM Ester.

Staining brain slices with acetoxymethyl ester (AM) Ca2+ dyes is a straightforward procedure to load multiple cells, and Fluo-4 is a commonly used high-affinity indicator due to its very large dynamic range. It has been shown that this dye preferentially stains glial cells, providing slow and large Ca2+ transients, but it is questionable whether and at which temporal resolution it can also report Ca2+ transients from neuronal cells. Here, by electrically stimulating mouse hippocampal slices, we resolved fast neuronal signals corresponding to 1%-3% maximal fluorescence changes. Specifically, by recording Ca2+ fluorescence at 2000 frames/s from multiple sites both in the CA3 and in the CA1 regions, we observed that the signal measured near the stimulating electrode, positioned on the mossy fibre pathway, was not blocked by perfusion with 10 μM NBQX and 50 μM AP5, preventing excitatory synaptic transmission. In contrast, this signal was fully blocked by additional perfusion with 1 μM tetrodotoxin, inhibiting voltage-gated Na+ channels and neuronal action potentials. We also present recordings obtained in the presence of 10 μM of the GABAA receptor antagonist bicuculline, or of 50 μM of the voltage-gated K+ channel inhibitor 4-aminopyridine, exhibiting a wide propagation of the signal from CA3 to CA1 regions under conditions that mimic epileptic seizures. Altogether, while Fluo-4 AM remains a preferable indicator for reporting Ca2+ signals from astrocytes at slow temporal resolution, we demonstrated that it can be also utilised for analysing fast neuronal network activity elicited by electrical stimulation in brain slices.

A review on recent advancement and pharmacological management of migraine

Modern theories suggest that the primary disorder in migraine takes place within the CNS and that this inspires adjustments in blood vessels within pain-producing intracranial meningeal systems that deliver upward push to headache pain. Migraine is now concept of as a neurovascular ailment it has been proposed that genetic abnormalities may be answerable for changing the response threshold to migraine particular trigger elements in the mind of a migraine compared to a normal individual. the exact nature of the principal disorder that is produced in migraine continues to be not clear and can contain spreading despair-like phenomena and activation of mind stem monoaminergic nuclei that are a part of the primary autonomic, vascular and ache control facilities. it is commonly notion that local vasodilatation of intracranial extracerebral blood vessels and a consequent stimulation of surrounding trigeminal sensory nervous ache pathways is a key mechanism underlying the era of headache ache related to migraine. This activation of the Trigeminovascular device’ is idea to reason the release of vasoactive sensory neuropeptides, mainly CGRP, that boom the ache reaction. The activated trigeminal nerves deliver nociceptive records to significant neurons within the mind stem trigeminal sensory nuclei that in turn relay the ache alerts to better facilities in which headache pain is perceived. it's been hypothesized that these significant neurons may become sensitized as a migraine assault progresses.The ‘triptan’ anti-migraine marketers (e.g. sumatriptan, rizatriptan, zolmitriptan naratriptan) are serotonergic agonists which have been proven to act selectively via inflicting vasoconstriction through 5-HT1B receptors which are expressed in human intracranial arteries and by way of inhibiting nociceptive transmission via an movement at five-HT1D receptors on peripheral trigeminal sensory nerve terminals within the meninges and crucial terminals in brain stem sensory nuclei. these 3 complementary web sites of movement underlie the clinical effectiveness of the 5-HT1B/1D agonists towards migraine headache pain and its related signs and symptoms

Integrating Metabolomics and Transcriptomics to Analyse and Reveal the Regulatory Mechanisms of Mung Bean Polyphenols on Intestinal Cell Damage Under Different Heat Stress Temperatures.

Polyphenols represent a new strategy of dietary intervention for heat stress regulation. The metabolic and genetic effects of three heat stress-regulated mung bean polyphenols on mouse small intestinal epithelial Mode-k cells were investigated by metabolomics-transcriptomics correlation analysis at different heat stress levels. Lipid metabolism, energy metabolism, and nervous system pathways were the key metabolic regulatory pathways. Under the heat stresses of 39 °C, 41 °C, and 43 °C, the key pathways regulated by mung bean polyphenols on intestinal epithelial Mode-k cells were choline metabolism, pyrimidine metabolism, and the retrograde endorphin signalling pathway in cancer, respectively. FoxO, Rap1, and PI3K-Akt signalling pathways were the key environmental regulatory signalling pathways. Mung bean polyphenols can alleviate heat stress-induced cells at 39 °C by inhibiting cell apoptosis and promoting lipid and amino acid accumulation. Mung bean polyphenols can alleviate the threat of cell death caused by heat stress at 41 °C by regulating heat shock proteins, inhibiting mitochondrial function and some nerve disease-related genes. The threat of cell death by heat stress at 43 °C can be alleviated by regulating nerve-related genes. This study confirmed that mung bean polyphenols can regulate heat stress. The results provide a reference for analysing the mechanism of dietary polyphenol regulating heat stress.

Autologous Serum and Recombinant Nerve Growth Factor in the Complex Treatment of Neurotrophic Keratitis

Neurotrophic keratitis is a frequent complication of neurosurgical interventions caused by a loss of corneal sensitivity due to damage of the trigeminal nerve pathway. The article presents a clinical case of a successful treatment of a neurotrophic corneal ulcer developed after removal of a giant trigeminal neurinoma. Treatment with autologous serum instillations made it possible to achieve ulcer healing and unstable corneal epithelialization. Stable epithelialization was achieved after temporary replacement of the autologous serum topical application with recombinant human nerve growth factor. In addition to ulcer healing and complete corneal epithelialization, regeneration of nerve fibers was noted (according to cornea confocal microscopy data).

Automated White Matter Fiber Tract Segmentation for the Brainstem

ABSTRACTThis study aimed to develop an automatic segmentation method for brainstem fiber bundles. We utilized the brainstem as a seed region for probabilistic tractography based on multishell, multitissue constrained spherical deconvolution in 40 subjects from the Human Connectome Project (HCP). All tractography data were registered into a common space to construct a brainstem fiber cluster atlas. A total of 100 fiber clusters were identified and annotated. Cortical parcellation–based fiber selection was then performed to extract fibers within the annotated clusters that projected to their corresponding cortical regions. This atlas was applied for automatic brainstem fiber bundle segmentation in 10 HCP subjects and 8 patients with brainstem cavernous malformations. The spatial overlap between automatic and manual reconstruction was assessed. Ultimately, eight fiber bundles were identified in the brainstem atlas on the basis of their trajectories: the corticospinal tract (CST), corticobulbar tract, frontopontine tract, parieto‐occipital‐pontine tract, medial lemniscus, and superior, middle, and inferior cerebellar peduncles. The mean and standard deviation of the weighted dice (wDice) scores between the automatic and manual reconstructions were 0.9076 ± 0.0950 for the affected CST, 0.9388 ± 0.0439 for the contralateral CST, 0.9130 ± 0.0588 for the affected medial lemniscus, and 0.9600 ± 0.0243 for the contralateral medial lemniscus. This proposed method effectively distinguishes major brainstem fiber bundles across subjects while reducing labor costs and interoperator variability inherent to manual reconstruction. Additionally, this method is robust in that it allows for the visualization and identification of fiber tracts surrounding brainstem cavernous malformations.

A novel approach in MRI signal processing for unveiling the intricacies of brain axonal organization.

This article introduces an innovative methodology to unveil the intricacies of white matter fiber pathways in the brain using diffusion MRI. Relying on the rationale that traditional methods observe a significant decrease in signal intensity values in the direction of higher diffusivity, our novel approach strategically selects for diffusion-sensitizing gradient directions (dSGDs, representing the directions along which signals are generated) aligned with reduced signal intensities. By treating these selected directions as maximum diffusivity directions, we generate uniformly distributed gradient directions (GDs) around them, which are subsequently employed in the reconstruction process. This approach addresses the shortcomings of existing methods. It improves upon the uniform gradient directions (UGDs) approach, which suffers from gradient direction redundancy, and the adaptive gradient directions (AGDs) approach, which requires solving the linear system twice per voxel. Proposed method simultaneously addresses both limitations, offering a more efficient and streamlined process. The effectiveness of our proposedmethodology is rigorously evaluated through simulations and experiments involving real data, showcasing its superior performance in uncovering the complex white matter fiber pathways in the brain.

Identification and Characterization of the Y-Organ of Orange Mud Crab Scylla Olivacea.

The Y-organs (YOs) synthesize and secrete molting hormones, and thus regulate crustacean growth and reproduction. However, the YOs of the orange mud crab Scylla olivacea is yet to be described due to its minute size and ambiguous feature. This study describes the location, morphological characteristics, histology, and the changes of YOs at different molt stages, and examines invitro ecdysteroid secreted by the YOs of S. olivacea. Mature male crabs (> 90 mm carapace width, CW) were used to identify the location of the YOs while male juveniles (50-65 mm CW) at three molt stages (intermoult, premoult, postmoult) were dissected for the characterization of 20-Hydroxyecdysone (20E) levels. The yellowish-white, compact, and oval-shaped YOs are located in pairs at the anterior cephalothorax region, beneath the mandibular external adductor muscle, anterior to the branchial chamber space, and around the end of the nerve tract. The YOs index and YO's cell diameter increased from postmoult to premoult; YO's diameter increased only during premoult stage. Under electron microscopy, the YO's surface morphology is rough, bumpy, network-like, and porous, with several lacunar system tubules. High concentrations of haemolymph 20E during premoult correlated with the changes in the characteristics of YOs at this stage. The presence of ecdysteroid in YOs was confirmed by high performance liquid chromatography (HPLC). The characteristics of the YOs of S. olivacea are similar to the YO descriptions of other brachyurans. The successful identification and characterization of YOs will spearhead future research on understanding its role in molt regulation of mud crabs, consequently contributing to the development and progress of crab culture and soft-shell crab industries.

Regional differences in three-dimensional fiber organization, smooth muscle cell phenotype, and contractility in the pregnant mouse cervix.

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous contractions, distension had a minimal effect on contractility, and the upper cervix had forceful contractions in response to labor-inducing agents (oxytocin and prostaglandin E2). These findings identify regional differences in cervix contractility related to contractile SMC content and fiber organization, which could be targeted with diagnostic technologies and for therapeutic intervention.

Rationale and design of a large trial of perioperative ketamine for prevention of chronic post-surgical pain

BackgroundChronic post-surgical pain (CPSP) is recognised as one of the most common and debilitating complications of major surgery. Progression from acute to chronic pain after surgery involves sensitisation of central nervous system pathways with the N-methyl-D-aspartate (NMDA) receptor having a central role. Ketamine is a potent, non-selective NMDA antagonist commonly used for management of acute postoperative pain. Inconsistent but largely supportive evidence from small trials of a preventative effect of perioperative ketamine on CPSP risk suggests that a confirmative large trial is needed.MethodsThe ROCKet (Reduction Of Chronic Post-surgical Pain with Ketamine) Trial is a multicentre, double-blind, placebo-controlled, individually randomised superiority trial conducted in 36 hospitals across Australia, New Zealand, and Hong Kong. The trial aims to recruit 4884 patients undergoing abdominal, thoracic, or major orthopaedic surgery. Eligible participants are randomised equally to perioperative intravenous ketamine or placebo for up to 72 h. Incidence of pain in the area of the index surgery is measured by structured telephone interview at 3 months (primary trial endpoint) and 12 months. Pain severity, nature, and associated psychological and quality of life indices are measured using the modified Brief Pain Inventory short form, Neuropathic Pain Questionnaire, Kessler K-10 Psychological Distress Scale, Pain Catastrophising Scale, EQ-5D-3L, and measures of healthcare utilisation and costs. The trial is being conducted by the Department of Critical Care, University of Melbourne, and the Australian and New Zealand College of Anaesthetists Clinical Trials Network. The trial is funded by the Australian National Health and Medical Research Council.DiscussionThe ROCKet trial will clarify the effectiveness of ketamine in primary prevention of CPSP. In addition, it will provide high-quality, prospective data on the epidemiology of CPSP which will better inform further research into prevention and management of CPSP.Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12617001619336) on the date of 12/11/2017.

Tay-Sachs and Sandhoff Diseases: Diffusion tensor imaging and correlational fiber tractography findings differentiate late-onset GM2 Gangliosidosis.

GM2 gangliosidosis is lysosomal storage disorder caused by deficiency of the heterodimeric enzyme β-hexosaminidase A. Tay-Sachs disease is caused by variants in HEXA encoding the α-subunit and Sandhoff disease is caused by variants in HEXB encoding the β-subunit. Due to shared clinical and biochemical findings, the two have been considered indistinguishable. We applied diffusion tensor imaging (DTI) and correlational fiber tractography to assess phenotypic differences in these two diseases. 40 DTI scans from 16 Late-Onset GM2 patients ( NCT00029965 ) with either Sandhoff (n = 4), or Tay-Sachs (n = 12) disease. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), and quantitative anisotropy (QA) were calculated in fiber tracts throughout the whole brain, arcuate fasciculus, corpus callosum, and cerebellum. Correlational tractography was also performed to identify fiber tracts with group wide differences in DTI metrics between Tay-Sachs and Sandhoff patients. A linear mixed effects model was used to analyze the differences between Tay-Sachs and Sandhoff patients. Tay-Sachs patients had higher MD in the left cerebellum ( p = 0.003703), right cerebellum ( p = 0.003435), superior cerebellar peduncle (SCP, p = 0.007332), and vermis ( p = 0.01007). Sandhoff patients had higher FA in the left cerebellum ( p = 0.005537), right cerebellum ( p = 0.01905), SCP ( p = 0.02844), and vermis ( p = 0.02469). Correlational fiber tractography identified fiber tracts almost exclusively in cerebellar pathways with higher FA and QA, and lower MD, AD, and RD in Sandhoff patients compared to Tay-Sachs patients. Our study shows neurobiological differences between these two related disorders. To our knowledge, this is the first study using correlational tractography in a lysosomal storage disorder demonstrating these differences. This result indicates a greater burden of cerebellar pathology in Tay-Sachs patients compared with Sandoff patients.

Forceps minor control of social behaviour.

The PRISM project, funded by the EU's Innovative Medicines Initiative, has identified a transdiagnostic, pathophysiological relationship between the integrity of the default mode network (DMN) and social dysfunction. To explore the causal link between DMN integrity and social behaviour, we employed a preclinical back-translation approach, using focal demyelination of the forceps minor to disrupt DMN connectivity in mice. By applying advanced techniques such as functional ultrasound imaging and automated analysis of social behaviour, we demonstrated that reduced DMN connectivity leads to impaired social interactions and increased anxiety in mice. Notably, these effects were reversible, indicating that the forceps minor, a critical fibre tract connecting key DMN regions in the prefrontal cortex, plays a crucial role in social function. This study provides direct evidence for a causal relationship between DMN integrity and social dysfunction, with potential implications for developing targeted treatments in precision psychiatry.

Understanding Cognitive Aging Through White Matter: A Fixel-Based Analysis.

Diffusion-weighted imaging (DWI) has been frequently used to examine age-related deterioration of white matter microstructure and its relationship to cognitive decline. However, typical tensor-based analytical approaches are often difficult to interpret due to the challenge of decomposing and (mis)interpreting the impact of crossing fibers within a voxel. We hypothesized that a novel analytical approach capable of resolving fiber-specific changes within each voxel (i.e., fixel-based analysis [FBA])-would show greater sensitivity relative to the traditional tensor-based approach for assessing relationships between white matter microstructure, age, and cognitive performance. To test our hypothesis, we studied 636 cognitively normal adults aged 65-80 years (mean age = 69.8 years; 71% female) using diffusion-weighted MRI. We analyzed fixels (i.e., fiber-bundle elements) to test our hypotheses. A fixel provides insight into the structural integrity of individual fiber populations in each voxel in the presence of multiple crossing fiber pathways, allowing for potentially increased specificity over other diffusion measures. Linear regression was used to investigate associations between each of three fixel metrics (fiber density, cross-section, and density × cross-section) with age and cognitive performance. We then compared and contrasted the FBA results to a traditional tensor-based approach examining voxel-wise fractional anisotropy. In a whole-brain analysis, significant associations were found between fixel-based metrics and age after adjustments for sex, education, total brain volume, site, and race. We found that increasing age was associated with decreased fiber density and cross-section, namely in the fornix, striatal, and thalamic pathways. Further analysis revealed that lower fiber density and cross-section were associated with poorer performance in measuring processing speed and attentional control. In contrast, the tensor-based analysis failed to detect any white matter tracts significantly associated with age or cognition. Taken together, these results suggest that FBAs of DWI data may be more sensitive for detecting age-related white matter changes in an older adult population and can uncover potentially clinically important associations with cognitive performance.

Reduced Neurite Arborization in Primary Dopaminergic Neurons in Autism-Like Shank3B-Deficient Mice.

Despite many studies on dopamine changes in autism, specific alterations in midbrain dopamine neurons projecting to the striatum and cortex remain unclear. Mouse models with diverse SH3 domain and ankyrin repeat containing protein 3 (Shank3) deficiencies are used for investigating autistic symptoms and underlying neurobiological mechanisms. SHANK3 belongs to postsynaptic proteins crucial for synapse formation during development, and disruptions in SHANK3 structure could lead to impaired neurite outgrowth and altered dendritic arborization and morphology. Therefore, we aimed to investigate whether Shank3 deficiency (Shank3B) leads to changes in the morphology of primary neuronal cell cultures from dopaminergic brain regions of neonatal mouse pups and whether it results in alterations in synaptic proteins in dopaminergic nerve pathway projection areas (striatum, frontal cortex). Significantly reduced neurite outgrowth was observed in primary dopaminergic neurons from the midbrain and striatum of Shank3-deficient compared to WT mice. A decrease in Synapsin I immunofluorescence signal in the cortical neurons isolated from Shank3-deficient mice was found, although neurite arborization changes were less severe. Importantly, the deficit in the length of the longest neurite was confirmed in primary cortical neurons isolated from Shank3-deficient mice. No changes in the gene expression of synaptic proteins were observed in the striatum and frontal cortex of Shank3-deficient mice, but an altered gene expression profile of dopaminergic receptors was found. These results show structural changes of dopaminergic neurons, which may explain autistic symptomatology in the used model and provide a basis for understanding the long-term development of autistic symptoms.

Peaks and Distributions of White Matter Tract-related Strains in Bicycle Helmeted Impacts: Implication for Helmet Ranking and Optimization.

Traumatic brain injury (TBI) in cyclists is a growing public health problem, with helmets being the major protection gear. Finite element head models have been increasingly used to engineer safer helmets often by mitigating brain strain peaks. However, how different helmets alter the spatial distribution of brain strain remains largely unknown. Besides, existing research primarily used maximum principal strain (MPS) as the injury parameter, while white matter fiber tract-related strains, increasingly recognized as effective predictors for TBI, have rarely been used for helmet evaluation. To address these research gaps, we used an anatomically detailed head model with embedded fiber tracts to simulate fifty-one helmeted impacts, encompassing seventeen bicycle helmets under three impact locations. We assessed the helmet performance based on four tract-related strains characterizing the normal and shear strain oriented along and perpendicular to the fiber tract, as well as the prevalently used MPS. Our results showed that both the helmet model and impact location affected the strain peaks. Interestingly, we noted that differenthelmets did not alter strain distribution, except for one helmet under one specific impact location. Moreover, our analyses revealed that helmet ranking outcome based on strain peaks was affected by the choice of injury metrics (Kendall's Tau coefficient: 0.58-0.93). Significant correlations were noted between tract-related strains and angular motion-based injury metrics. This study provided new insights into computational brain biomechanics and highlighted the helmet ranking outcome was dependent on the choice of injury metrics. Our results also hinted that the performance of helmets could be augmented by mitigating the strain peak and optimizing the strain distribution with accounting the selective vulnerability of brain subregionsand more research was needed to develop region-specific injury criteria.

Alterations of White Matter Microstructure in Migraine Patients Vary in the Peri-ictal Phases.

Alterations in white matter (WM) microstructure are commonly found in migraine patients. Here, we employ a longitudinal study of episodic migraine without aura using diffusion magnetic resonance imaging (dMRI) to investigate whether such WM microstructure alterations vary through the different phases of the pain cycle. Fourteen patients with episodic migraine without aura related with menstruation were scanned through four phases of their (spontaneous) migraine cycle (interictal, preictal, ictal, and postictal). Fifteen healthy controls were studied in the corresponding phases of the menstrual cycle. Multishell dMRI data were acquired and preprocessed to obtain maps of diffusion parameters reflecting WM microstructure. After a whole-brain analysis comparing patients with controls, a region-of-interest analysis was performed to determine whether the patients' microstructural changes varied across the migraine cycle in specific WM tracts. Compared with controls, patients showed reduced axial diffusivity (AD) in several WM tracts across the whole brain in the interictal phase and increased fractional anisotropy (FA) in commissural fibers in the ictal phase. Interestingly, AD returned to baseline levels during peri-ictal phases in specific projection and association fibers. In contrast, FA values decreased in the ictal phase away from normal values in a few commissural and projection tracts. Widespread WM fiber tracts suffer structural variations across the migraine cycle, suggesting microstructural changes potentially associated with limbic and salience functional networks and highlighting the importance of the cycle phase in imaging studies of migraine.

Optimized uniform sampling and validation of fiber tracts from magnetic resonance tractography for in vivo architectural measurement of human forearm muscles.

In vivo muscle architectural parameters can be calculated from the fiber tracts using magnetic resonance (MR) tractography. However, the reconstructed tracts may be unevenly distributed within the muscle volume and there lacks commonly used metric to quantitatively evaluate the validity of the tracts. Our objective is to measure forearm muscle architecture by uniformly sampling fiber tracts from the candidate streamlines in MR tractography and validate the reconstructed fiber tracts qualitatively and quantitatively. We proposed farthest streamline sampling (FSS) to uniformly sample fiber tracts from the candidate streamlines. The method was evaluated on the MR data acquired from 12 healthy subjects for 17 forearm muscles and was compared with two conventional methods through uniform coverage performance. Anatomical correctness was verified by: 1. visually assessing fiber orientation, 2. checking whether architectural parameters were within physiological ranges and 3. classifying architectural types. The proposed FSS yielded optimal uniform coverage performance among the three methods (P<0.05). FSS reduced the sampling of long tracts (10% fiber length reduction, P<0.05), and the estimated architectural parameters were within the physiological ranges (P<0.05). The tractography visually matched cadaveric specimens. The architectural types of 16 muscles were correctly classified except for the palmaris longus, which exhibited a linear arrangement of fiber endpoints (R2 = 0.95±0.02, P<0.001). The proposed FSS method reconstructed uniformly distributed fiber tracts and the anatomical correctness of the reconstructed tracts was verified. The novel methods allow for accurate in vivo muscle architectural measurement, which was demonstrated through the characterization of architectural properties in human forearm muscles.