Connectomic insights into the impact of 1p/19q co-deletion in dominant hemisphere insular glioma patients.

Objectives: This study aimed to elucidate the influences of 1p/19q co-deletion on structural connectivity alterations in patients with dominant hemisphere insular diffuse gliomas. Methods: We incorporated 32 cases of left insular gliomas and 20 healthy controls for this study. Using diffusion MRI, we applied correlational tractography, differential tractography, and graph theoretical analysis to explore the potential connectivity associated with 1p/19q co-deletion. Results: The study revealed that the quantitative anisotropy (QA) of key deep medial fiber tracts, including the anterior thalamic radiation, superior thalamic radiation, fornix, and cingulum, had significant negative associations with 1p/19q co-deletion (FDR = 4.72 × 10-5). These tracts are crucial in maintaining the integrity of brain networks. Differential analysis further supported these findings (FWER-corrected p < 0.05). The 1p/19q non-co-deletion group exhibited significantly higher clustering coefficients (FDR-corrected p < 0.05) and reduced betweenness centrality (FDR-corrected p < 0.05) in regions around the tumor compared to HC group. Graph theoretical analysis indicated that non-co-deletion patients had increased local clustering and decreased betweenness centrality in peritumoral brain regions compared to co-deletion patients and healthy controls (FDR-corrected p < 0.05). Additionally, despite not being significant through correction, patients with 1p/19q co-deletion exhibited lower trends in weighted average clustering coefficient, transitivity, small worldness, and global efficiency, while showing higher tendencies in weighted path length compared to patients without the co-deletion. Conclusion: The findings of this study underline the significant role of 1p/19q co-deletion in altering structural connectivity in insular glioma patients. These alterations in brain networks could have profound implications for the neural functionality in patients with dominant hemisphere insular gliomas.

A sensorimotor-association axis of thalamocortical connection development.

Human cortical development follows a sensorimotor-to-association sequence during childhood and adolescence1-6. The brain's capacity to enact this sequence over decades indicates that it relies on intrinsic mechanisms to regulate inter-regional differences in the timing of cortical maturation, yet regulators of human developmental chronology are not well understood. Given evidence from animal models that thalamic axons modulate windows of cortical plasticity7-12, here we evaluate the overarching hypothesis that structural connections between the thalamus and cortex help to coordinate cortical maturational heterochronicity during youth. We first introduce, cortically annotate, and anatomically validate a new atlas of human thalamocortical connections using diffusion tractography. By applying this atlas to three independent youth datasets (ages 8-23 years; total N = 2,676), we reproducibly demonstrate that thalamocortical connections develop along a maturational gradient that aligns with the cortex's sensorimotor-association axis. Associative cortical regions with thalamic connections that take longest to mature exhibit protracted expression of neurochemical, structural, and functional markers indicative of higher circuit plasticity as well as heightened environmental sensitivity. This work highlights a central role for the thalamus in the orchestration of hierarchically organized and environmentally sensitive windows of cortical developmental malleability.

Unveiling the axonal connectivity between the precuneus and temporal pole: Structural evidence from the cingulum pathways.

Neuroimaging studies have consistently demonstrated concurrent activation of the human precuneus and temporal pole (TP), both during resting-state conditions and various higher-order cognitive functions. However, the precise underlying structural connectivity between these brain regions remains uncertain despite significant advancements in neuroscience research. In this study, we investigated the connectivity of the precuneus and TP by employing parcellation-based fiber micro-dissections in human brains and fiber tractography techniques in a sample of 1065 human subjects and a sample of 41 rhesus macaques. Our results demonstrate the connectivity between the posterior precuneus area POS2 and the areas 35, 36, and TG of the TP via the fifth subcomponent of the cingulum (CB-V) also known as parahippocampal cingulum. This finding contributes to our understanding of the connections within the posteromedial cortices, facilitating a more comprehensive integration of anatomy and function in both normal and pathological brain processes. PRACTITIONER POINTS: Our investigation delves into the intricate architecture and connectivity patterns of subregions within the precuneus and temporal pole, filling a crucial gap in our knowledge. We revealed a direct axonal connection between the posterior precuneus (POS2) and specific areas (35, 35, and TG) of the temporal pole. The direct connections are part of the CB-V pathway and exhibit a significant association with the cingulum, SRF, forceps major, and ILF. Population-based human tractography and rhesus macaque fiber tractography showed consistent results that support micro-dissection outcomes.

Establishing connectivity through microdissections of midbrain stimulation-related neural circuits.

Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomofunctional mechanisms governing human behaviour, in addition to the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. Although the ventral tegmental area has been targeted successfully with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region is not fully understood. Here, using fibre microdissections in human cadaveric hemispheres, population-based high-definition fibre tractography and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain and prefrontal cortex, which is implicated in the treatment of obsessive-compulsive disorder, major depressive disorder, Alzheimer's disease, cluster headaches and aggressive behaviours.

brainlife.io: a decentralized and open-source cloud platform to support neuroscience research.

Neuroscience is advancing standardization and tool development to support rigor and transparency. Consequently, data pipeline complexity has increased, hindering FAIR (findable, accessible, interoperable and reusable) access. brainlife.io was developed to democratize neuroimaging research. The platform provides data standardization, management, visualization and processing and automatically tracks the provenance history of thousands of data objects. Here, brainlife.io is described and evaluated for validity, reliability, reproducibility, replicability and scientific utility using four data modalities and 3,200 participants.

Diffusion and functional MRI in surgical neuromodulation.

Surgical neuromodulation has witnessed significant progress in recent decades. Notably, deep brain stimulation (DBS), delivered precisely within therapeutic targets, has revolutionized the treatment of medication-refractory movement disorders and is now expanding for refractory psychiatric disorders, refractory epilepsy, and post-stroke motor recovery. In parallel, the advent of incisionless treatment with focused ultrasound ablation (FUSA) can offer patients life-changing symptomatic relief. Recent research has underscored the potential to further optimize DBS and FUSA outcomes by conceptualizing the therapeutic targets as critical nodes embedded within specific brain networks instead of strictly anatomical structures. This paradigm shift was facilitated by integrating two imaging modalities used regularly in brain connectomics research: diffusion MRI (dMRI) and functional MRI (fMRI). These advanced imaging techniques have helped optimize the targeting and programming techniques of surgical neuromodulation, all while holding immense promise for investigations into treating other neurological and psychiatric conditions. This review aims to provide a fundamental background of advanced imaging for clinicians and scientists, exploring the synergy between current and future approaches to neuromodulation as they relate to dMRI and fMRI capabilities. Focused research in this area is required to optimize existing, functional neurosurgical treatments while serving to build an investigative infrastructure to unlock novel targets to alleviate the burden of other neurological and psychiatric disorders.

White matter microstructure organization across the transition to fatherhood.

The transition to parenthood remains an understudied window of potential neuroplasticity in the adult brain. White matter microstructural (WMM) organization, which reflects structural connectivity in the brain, has shown plasticity across the lifespan. No studies have examined how WMM organization changes from the prenatal to postpartum period in men becoming fathers. This study investigates WMM organization in men transitioning to first-time fatherhood. We performed diffusion-weighted imaging to identify differences in WMM organization, as indexed by fractional anisotropy (FA). We also investigated whether FA changes were associated with fathers' postpartum mental health. Associations between mental health and WMM organization have not been rarely examined in parents, who may be vulnerable to mental health problems. Fathers exhibited reduced FA at the whole-brain level, especially in the cingulum, a tract associated with emotional regulation. Fathers also displayed reduced FA in the corpus callosum, especially in the forceps minor, which is implicated in cognitive functioning. Postpartum depressive symptoms were linked with increases and decreases in FA, but FA was not correlated with perceived or parenting stress. Findings provide novel insight into fathers' WMM organization during the transition to parenthood and suggest postpartum depression may be linked with fathers' neuroplasticity during the transition to parenthood.

An Open Resource: MR and light sheet microscopy stereotaxic atlas of the mouse brain.

We have combined MR histology and light sheet microscopy (LSM) of five postmortem C57BL/6J mouse brains in a stereotaxic space based on micro-CT yielding a multimodal 3D atlas with the highest spatial and contrast resolution yet reported. Brains were imaged in situ with multi gradient echo (mGRE) and diffusion tensor imaging (DTI) at 15 µm resolution (∼ 2.4 million times that of clinical MRI). Scalar images derived from the average DTI and mGRE provide unprecedented contrast in 14 complementary 3D volumes, each highlighting distinct histologic features. The same tissues scanned with LSM and registered into the stereotaxic space provide 17 different molecular cell type stains. The common coordinate framework labels (CCFv3) complete the multimodal atlas. The atlas has been used to correct distortions in the Allen Brain Atlas and harmonize it with Franklin Paxinos. It provides a unique resource for stereotaxic labeling of mouse brain images from many sources.

Probabilistic coverage of the frontal aslant tract in young adults: Insights into individual variability, lateralization, and language functions.

The frontal aslant tract (FAT) is a crucial neural pathway of language and speech, but little is known about its connectivity and segmentation differences across populations. In this study, we investigate the probabilistic coverage of the FAT in a large sample of 1065 young adults. Our primary goal was to reveal individual variability and lateralization of FAT and its structure-function correlations in language processing. The study utilized diffusion MRI data from 1065 subjects obtained from the Human Connectome Project. Automated tractography using DSI Studio software was employed to map white matter bundles, and the results were examined to study the population variation of the FAT. Additionally, anatomical dissections were performed to validate the fiber tracking results. The tract-to-region connectome, based on Human Connectome Project-MMP parcellations, was utilized to provide population probability of the tract-to-region connections. Our results showed that the left anterior FAT exhibited the most substantial individual differences, particularly in the superior and middle frontal gyrus, with greater variability in the superior than the inferior region. Furthermore, we found left lateralization in FAT, with a greater difference in coverage in the inferior and posterior portions. Additionally, our analysis revealed a significant positive correlation between the left FAT inferior coverage area and the performance on the oral reading recognition (p = .016) and picture vocabulary (p = .0026) tests. In comparison, fractional anisotropy of the right FAT exhibited marginal significance in its correlation (p = .056) with Picture Vocabulary Test. Our findings, combined with the connectivity patterns of the FAT, allowed us to segment its structure into anterior and posterior segments. We found significant variability in FAT coverage among individuals, with left lateralization observed in both macroscopic shape measures and microscopic diffusion metrics. Our findings also suggested a potential link between the size of the left FAT's inferior coverage area and language function tests. These results enhance our understanding of the FAT's role in brain connectivity and its potential implications for language and executive functions.

Associations of depression and perceived physical fatigability with white matter integrity in older adults.

BACKGROUNDS: Fatigability is prevalent in older adults. However, it is often associated with depressed mood. We aim to investigate these two psychobehavioral constructs by examining their underpinning of white matter structures in the brain and their associations with different medical conditions. METHODS: Twenty-seven older adults with late-life depression (LLD) and 34 cognitively normal controls (CN) underwent multi-shell diffusion MRI. Fatigability was measured with the Pittsburgh Fatigability Scale. We examined white matter integrity by measuring the quantitative anisotropy (QA), a fiber tracking parameter with better accuracy than the traditional imaging technique. RESULTS: We found those with LLD had lower QA in the 2nd branch of the left superior longitudinal fasciculus (SLF-II), and those with more physical fatigability had lower QA in more widespread brain regions. In tracts associated with more physical fatigability, the lower QA in left acoustic radiation and left superior thalamic radiation correlated with higher blood glucose (r = - 0.46 and - 0.49). In tracts associated with depression, lower QA in left SLF-II correlated with higher bilirubin level (r = - 0.58). DISCUSSION: Depression and fatigability were associated with various white matter integrity changes, which correlated with biochemistry biomarkers all related to inflammation.

Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation.

Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourette's syndrome, the supplementary motor area in Parkinson's disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain.

Assessing Postoperative Motor Risk in Insular Low-Grade Gliomas Patients: The Potential Role of Presurgery MRI Corticospinal Tract Shape Measures.

BACKGROUND: Insular low-grade gliomas (LGGs) are surgically challenging due to their proximity to critical structures like the corticospinal tract (CST). PURPOSE: This study aims to determine if preoperative CST shape metrics correlate with postoperative motor complications in insular LGG patients. STUDY TYPE: Retrospective. POPULATION: 42 patients (mean age 40.26 ± 10.21 years, 25 male) with insular LGGs. FIELD STRENGTH/SEQUENCE: Imaging was performed using 3.0 Tesla MRI, incorporating T1-weighted magnetization-prepared rapid gradient-echo, T2-weighted space dark-fluid with spin echo (SE), and diffusional kurtosis imaging (DKI) with gradient echo sequences, all integrated with echo planar imaging. ASSESSMENT: Shape metrics of the CST, including span, irregularity, radius, and irregularity of end regions (RER and IER, respectively), were compared between the affected and healthy hemispheres. Total end region radius (TRER) was determined as the sum of RER 1 and RER 2. The relationships between shape metrics and postoperative short-term (4 weeks) and long-term (>8 weeks) motor disturbances assessing by British Medical Research Council grading system, was analyzed using multivariable regression models. STATISTICAL TESTING: Paired t-tests compared CST metrics between hemispheres. Logistic regression identified associations between these metrics and motor disturbances. The models were developed using all available data and there was no independent validation dataset. Significance was set at P < 0.05. RESULTS: Short-term motor disturbance risk was significantly related to TRER (OR = 199.57). Long-term risk significantly correlated with IER 1 (OR = 59.84), confirmed as a significant marker with an AUC of 0.78. Furthermore, the CST on the affected side significantly had the greater irregularity, larger TRER and RER 1, and smaller span compared to the healthy side. DATA CONCLUSION: Preoperative evaluation of TRER and IER 1 metrics in the CST may serve as a tool for assessing the risk of postoperative motor complications in insular LGG patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Functional and structural connectivity correlates of semantic verbal fluency deficits in first-episode psychosis.

INTRODUCTION: Semantic verbal fluency (SVF) impairments are debilitating and present early in the course of psychotic illness. Deficits within frontal, parietal, and temporal brain regions contribute to this deficit, as long-range communication across this functionally integrated network is critical to SVF. This study sought to isolate disruptions in functional and structural connectivity contributing to SVF deficits during first-episode psychosis in the schizophrenia spectrum (FESz). METHODS: Thirty-three FESz and 34 matched healthy controls (HC) completed the Animal Naming Task to assess SVF. Magnetoencephalography was recorded during an analogous covert SVF task, and phase-locking value (PLV) used to measure functional connectivity between inferior frontal and temporoparietal structures bilaterally. Diffusion imaging was collected to measure fractional anisotropy (FA) of the arcuate fasciculus, the major tract connecting frontal and temporoparietal language areas. RESULTS: SVF scores were lower among FESz compared to HC. While PLV and FA did not differ between groups overall, FESz exhibited an absence of the left-lateralized nature of both measures observed in HC. Among FESz, larger right-hemisphere PLV was associated with worse SVF performance (ρ = -0.51) and longer DUP (ρ = -0.50). DISCUSSION: In addition to worse SVF, FESz exhibited diminished leftward asymmetry of structural and functional connectivity in fronto-temporoparietal SVF network. The relationship between theta-band hyperconnectivity and poorer performance suggests a disorganized executive network and may reflect dysfunction of frontal cognitive control centers. These findings illustrate an aberrant pattern across the distributed SVF network at disease onset and merit further investigation into development of asymmetrical hemispheric connectivity and its failure among high-risk populations.

Exploring MGMT methylation-driven structural connectivity changes in insular gliomas: a tractography and graph theoretical analysis.

OBJECTIVES: This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres. METHODS: We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level. RESULTS: The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.019) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides. CONCLUSION: Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.

The anatomy of the four streams of the prefrontal cortex. Preliminary evidence from a population based high definition tractography study.

The model of the four streams of the prefrontal cortex proposes 4 streams of information: motor through Brodmann area (BA) 8, emotion through BA 9, memory through BA 10, and emotional-related sensory through BA 11. Although there is a surge of functional data supporting these 4 streams within the PFC, the structural connectivity underlying these neural networks has not been fully clarified. Here we perform population-based high-definition tractography using an averaged template generated from data of 1,065 human healthy subjects acquired from the Human Connectome Project to further elucidate the structural organization of these regions. We report the structural connectivity of BA 8 with BA 6, BA 9 with the insula, BA 10 with the hippocampus, BA 11 with the temporal pole, and BA 11 with the amygdala. The 4 streams of the prefrontal cortex are subserved by a structural neural network encompassing fibers of the anterior part of the superior longitudinal fasciculus-I and II, corona radiata, cingulum, frontal aslant tract, and uncinate fasciculus. The identified neural network of the four streams of the PFC will allow the comprehensive analysis of these networks in normal and pathological brain function.

A preliminary study on corticospinal tract morphology in incidental and symptomatic insular low-grade glioma: implications for post-surgical motor outcomes.

OBJECTIVE: Our study aimed to investigate the shape and diffusion properties of the corticospinal tract (CST) in patients with insular incidental and symptomatic low-grade gliomas (LGGs), especially those in the incidental group, and evaluate their association with post-surgical motor function. METHODS: We performed automatic fiber tracking on 41 LGG patients, comparing macroscopic shape and microscopic diffusion properties of CST between ipsilateral and contralateral tracts in both incidental and symptomatic groups. A correlation analysis was conducted between properties of CST and post-operative motor strength grades. RESULTS: In the incidental group, no significant differences in mean diffusion properties were found between bilateral CST. While decreased anisotropy of the CST around the superior limiting sulcus and increased axial diffusivity of the CST near the midbrain level were noted, there was no significant correlation between pre-operative diffusion metrics and post-operative motor strength. In comparison, we found significant correlations between the elongation of the affected CST in the preoperative scans and post-operative motor strength in short-term and long-term follow ups (p = 1.810 × 10-4 and p = 9.560 × 10-4, respectively). CONCLUSIONS: We found a significant correlation between CST shape measures and post-operative motor function outcomes in patients with incidental insular LGGs. CST morphology shows promise as a potential prognostic factor for identifying functional deficits in this patient population.

Mapping the Impact of Approximate Gradient Nonlinearity Fields Correction on Tractography.

Nonlinear gradients impact diffusion weighted MRI by introducing spatial variation in estimated diffusion tensors. Recent studies have shown that increasing signal-to-noise ratios and the use of ultra-strong gradients may lead to clinically significant impacts on analyses due to these nonlinear gradients in microstructural measures. These effects can potentially bias tractography results and cause misinterpretation of data. Herein, we characterize the impact of an "approximate" gradient nonlinearity correction technique in tractography using empirically derived gradient nonlinear fields. This technique scales the diffusion signal by the change in magnitude due to the gradient nonlinearities, without concomitant correction of gradient direction errors. The impact of this correction on tractography is assessed through white matter bundle segmentation and connectomics via bundle-wise volume, fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity, primary eigenvector, and length; as well as the modularity, global efficiency, and characteristic path length connectomics graph measures. We investigate the differences between (1) these measures directly and (2) the within session variability of these measures before and after approximate correction in 61 subjects from the MASiVar pediatric reproducibility dataset. We find approximate correction results is little to no differences on the population level, but large differences on the subject-specific level for both the measures directly and their within session variability. Thus, this study suggests though approximate correction of gradient nonlinearities may not change tractography findings on the population level, subject-specific interpretations may exhibit large fluctuations. A limitation is the lack of comparison with the empirical voxel-wise gradient table correction.

Brain MRI Segmentation using Template-Based Training and Visual Perception Augmentation.

Deep learning models usually require sufficient training data to achieve high accuracy, but obtaining labeled data can be time-consuming and labor-intensive. Here we introduce a template-based training method to train a 3D U-Net model from scratch using only one population-averaged brain MRI template and its associated segmentation label. The process incorporated visual perception augmentation to enhance the model's robustness in handling diverse image inputs and mitigating overfitting. Leveraging this approach, we trained 3D U-Net models for mouse, rat, marmoset, rhesus, and human brain MRI to achieve segmentation tasks such as skull-stripping, brain segmentation, and tissue probability mapping. This tool effectively addresses the limited availability of training data and holds significant potential for expanding deep learning applications in image analysis, providing researchers with a unified solution to train deep neural networks with only one image sample.

Differential and correlational tractography as tract-based biomarkers in mild traumatic brain injury: A longitudinal MRI study.

We evaluated the fiber bundles in mild traumatic brain injury (mTBI) patients using differential and correlational tractography in a longitudinal analysis. Diffusion MRI data were acquired in 34 mTBI patients at 7 days (acute stage) and 3 months or longer (chronic stage) after mTBI. Trail Making Test A (TMT-A) and Digital Symbol Substitution Test changes were used to evaluate the cognitive performance. Longitudinal correlational tractography showed decreased anisotropy in the corpus callosum during the chronic mTBI stage. The changes in anisotropy in the corpus callosum were significantly correlated with the changes in TMT-A (false discovery rate [FDR] = 0.000094). Individual longitudinal differential tractography found that anisotropy decreased in the corpus callosum in 30 mTBI patients. Group cross-sectional differential tractography found that anisotropy increased (FDR = 0.02) in white matter in the acute mTBI patients, while no changes occurred in the chronic mTBI patients. Our study confirms the feasibility of using correlational and differential tractography as tract-based monitoring biomarkers to evaluate the disease progress of mTBI, and indicates that normalized quantitative anisotropy could be used as a biomarker to monitor the injury and/or repairs of white matter in individual mTBI patients.