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Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) is a circuit-based treatment for severe, refractory obsessive-compulsive disorder (OCD). The therapeutic effects of DBS are hypothesized to be mediated by direct modulation of a distributed cortico-striato-thalmo-cortical network underlying OCD symptoms. However, the exact underlying mechanism by which DBS exerts its therapeutic effects still remains unclear. In five participants receiving DBS for severe, refractory OCD (3 responders, 2 non-responders), we conducted a DBS On/Off cycling paradigm during the acquisition of functional MRI (23 fMRI runs) to determine the network effects of stimulation across a variety of bipolar configurations. We also performed tractography using diffusion-weighted imaging (DWI) to relate the functional impact of DBS to the underlying structural connectivity between active stimulation contacts and functional brain networks. We found that therapeutic DBS had a distributed effect, suppressing BOLD activity within regions such as the orbitofrontal cortex, dorsomedial prefrontal cortex, and subthalamic nuclei compared to non-therapeutic configurations. Many of the regions suppressed by therapeutic DBS were components of the default mode network (DMN). Moreover, the estimated stimulation field from the therapeutic configurations exhibited significant structural connectivity to core nodes of the DMN. Based upon these findings, we hypothesize that the suppression of the DMN by ALIC DBS is mediated by interruption of communication through structural white matter connections surrounding the DBS active contacts.

IntroductionWe investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle-aged adults.MethodsWe included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also had available brain MRI. Concentrations of leptin, soluble leptin receptor (sOB-R), and their ratio (free leptin index [FLI]), indicating leptin bioavailability, were measured using enzyme-linked immunosorbent assays. Cognitive and MRI measures were derived using standardized protocols.ResultsHigher sOB-R was associated with lower fractional anisotropy (FA, β = -0.114 ± 0.02, p

Recent work has identified a critical role for the hippocampus in reward-sensitive behaviors, including motivated memory, reinforcement learning, and decision-making. Animal histology and human functional neuroimaging have shown that brain regions involved in reward processing and motivation are more interconnected with the ventral/anterior hippocampus. However, direct evidence examining gradients of structural connectivity between reward regions and the hippocampus in humans is lacking. The present study used diffusion MRI (dMRI) and probabilistic tractography to quantify the structural connectivity of the hippocampus with key reward processing regions in vivo. Using a large sample of subjects (N = 628) from the human connectome dMRI data release, we found that connectivity profiles with the hippocampus varied widely between different regions of the reward circuit. While the dopaminergic midbrain (ventral tegmental area) showed stronger connectivity with the anterior versus posterior hippocampus, the ventromedial prefrontal cortex showed stronger connectivity with the posterior hippocampus. The limbic (ventral) striatum demonstrated a more homogeneous connectivity profile along the hippocampal long axis. This is the first study to generate a probabilistic atlas of the hippocampal structural connectivity with reward-related networks, which is essential to investigating how these circuits contribute to normative adaptive behavior and maladaptive behaviors in psychiatric illness. These findings describe nuanced structural connectivity that sets the foundation to better understand how the hippocampus influences reward-guided behavior in humans.

BACKGROUND: It is well-established that parental obesity is a strong risk factor for offspring obesity. Further, a converging body of evidence now suggests that maternal weight profiles may affect the developing offsprings brain in a manner that confers future obesity risk. Here, we investigated how pre-pregnancy maternal weight status influences the reward-related striatal areas of the offsprings brain during in utero development. METHODS: We used diffusion tensor imaging to quantify the microstructure of the striatal brain regions of interest in neonates (N = 116 [66 males, 50 females], mean gestational weeks at birth [39.88], SD = 1.14; at scan [43.56], SD = 1.05). Linear regression was used to test the associations between maternal pre-pregnancy body mass index (BMI) and infant striatal mean diffusivity. RESULTS: High maternal pre-pregnancy BMI was associated with higher mean MD values in the infants left caudate nucleus. Results remained unchanged after the adjustment for covariates. CONCLUSIONS: In utero exposure to maternal adiposity might have a growth-impairing impact on the mean diffusivity of the infants left caudate nucleus. Considering the involvement of the caudate nucleus in regulating eating behavior and food-related reward processing later in life, this finding calls for further investigations to define the prognostic relevance of early-life caudate nucleus development and weight trajectories of the offspring.

This study aimed to evaluate the effects of a 12-week intervention combining electroacupuncture (EA) with conventional cognitive rehabilitation (CR) on cognitive recovery and brain network topological properties in stroke patients. Thirty-four post-stroke cognitive impairment (PSCI) patients were randomly assigned to either an EA + CR group or a CR-only group, with both undergoing five weekly interventions for 12 weeks. Cognitive assessments and Diffusion Tensor Imaging tests were performed pre- and post-intervention. Primary outcomes included the Montreal Cognitive Assessment (MoCA), Digit Span Test (DST), Auditory Verbal Learning Test (AVLT-H), and Aphasia Screening Scale. Secondary outcomes measured brain network global and nodal properties. The EA + CR group showed significant improvements in MoCA (p < 0.001), AVLT-H (p = 0.004), and in areas like naming (p = 0.022), attention (p < 0.001), and delayed recall (p < 0.001). Local brain network metrics, such as clustering coefficients (Cp) and local efficiency (Eloc), were significantly higher (p < 0.05) in the EA + CR group, though global efficiency (Eglob) was unchanged. Improvements in Eloc were positively correlated with MoCA scores (r = 0.0716, p = 0.018). Specific brain regions, including the medial and paracentral cingulate gyrus, inferior temporal gyrus, and left supramarginal gyrus, exhibited significant nodal property differences, suggesting that EA may enhance cognitive recovery by targeting cognitively relevant regions. These findings indicate that EA, combined with CR, is a safe and effective treatment for cognitive impairment following stroke, potentially via structural brain network improvements. Clinical trial registration: https://clinicaltrials.gov/ , ChiCTR2200066160. [ABSTRACT FROM AUTHOR]

Purpose: To assess the predictive value of radiomics features extracted from structural MRI, dynamic contrast enhanced (DCE), and diffusion tensor imaging (DTI) in detecting O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with diffuse gliomas. Methods: Retrospective MRI data of 110 patients were enrolled in this study. The training dataset included 88 patients (mean age 52.84 ± 14.71, 47 females). The test dataset included 22 patients (mean age 50.64 ± 12.58, 12 females). A total of 2,782 radiomic features were extracted from structural MRI, DCE, and DTI within two region of interests (ROIs). Feature section was conducted using Pearson correlation and least absolute shrinkage and selection operator. Principal component analysis was utilized for dimensionality reduction. Support vector machine was employed for model construction. Two radiologists with 1 year and 5 years of experience evaluated the MGMT status in the test dataset as a comparison with the models. The chi-square test and independent samples t -test were used for assessing the statistical differences in patients' clinical characteristics. Results: On the training dataset, the model structural MRI + DCE achieved the highest AUC of 0.906. On the test dataset, the model structural MRI + DCE + DTI achieved the highest AUC of 0.868, outperforming two radiologists. Conclusion: The radiomics models have obtained promising performance in predicting MGMT promoter methylation status. Adding DCE and DTI features can provide extra information to structural MRI in detecting MGMT promoter methylation. [ABSTRACT FROM AUTHOR]

Objective: Amyotrophic lateral sclerosis (ALS) exhibits several different presentations and clinical phenotypes. Of these, classic ALS (ALS-Cl), which is the most common phenotype, presents with relatively equal amounts of upper motor neuron and lower motor neuron signs. Magnetic resonance imaging (MRI) provides a noninvasive way to assess central nervous system damage in these patients. To our knowledge no study is available where exploratory whole brain grey matter (GM) and white matter (WM) network analysis is performed considering only the ALS-Cl subgroup of ALS patients. Methods: GM voxel-based morphometry analysis and WM network analysis using graph theory was performed in the MRI dataset of 14 neurologic controls and 25 ALS-Cl patients. Results and Conclusions: No significant GM differences were observed between ALS-Cl and neurologic controls. WM network revealed significant (p < 0.05) reduction and increase in degree measure in several extramotor brain regions of ALS-Cl patients. Both global and local graph metrics revealed significant abnormal values in ALS-Cl patients when compared to neurologic controls. Significant WM changes in ALS-Cl patients with no significant GM changes suggest that neurodegeneration may onset as an "axonopathy" in this ALS subtype. [ABSTRACT FROM AUTHOR]

Background: The presence of diffuse brain damage in normal-appearing white matter (NAWM) and gray matter (NAGM) in neuromyelitis optica spectrum disorder (NMOSD) remains controversial. We aimed to address this controversy by applying a multiparametric MRI approach. Additionally, the association between MRI metrics and clinical variables was explored. Methods: In this cross-sectional study, we prospectively evaluated aquaporin-4-IgG positive NMOSD patients and healthy controls (HC) matched for age and sex. The clinical variables of interest were collected for each participant. The mean values of T1-w/T2-w ratio, magnetization transfer ratio (MTR), fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) were obtained in NAWM, NAGM, as well as in global and hypointense lesion masks. Global lesions refer to those typically associated with aquaporin-4-IgG positive NMOSD. Hypointense lesions were defined as areas of hypointense signal in both T1-w and fluid-attenuated inversion recovery (FLAIR) images. Results: In total, we included 105 participants (59 NMOSD patients and 46 HC). T1-w/T2-w ratio was lower in NAWM of NMOSD patients versus HC (1.83 ± 0.14 vs 1.89 ± 0.14; p = 0.029), while no significant differences were found in NAWM or NAGM across the other metrics: (p range: 0.079 to 0.973). Hypointense lesions showed lower T1-w/T2-w ratio, MTR, and FA, and higher diffusivity metrics as compared to global lesion masks (p < 0.001). T1-w/T2-w ratio in NAWM was inversely correlated with time to start immunosuppressive therapy (r = − 0.278; p = 0.036) and with MD (r = − 0.325; p = 0.014). Conclusion: Microstructural integrity loss seems to be confined to focal tissue damage in NMOSD. Decreased T1-w/T2-w ratio in NAWM may reflect subclinical water accumulation due to astrocyte and blood–brain barrier dysfunction. Hypointense lesions have shown a severe degree of microstructural damage. [ABSTRACT FROM AUTHOR]

The substantia nigra pars compacta (SNc), one of the main dopaminergic nuclei of the brain, exerts a regulatory function on the basal ganglia circuitry via the nigro-striatal pathway but its possible dopaminergic innervation of the thalamus has been only investigated in non-human primates. The impossibility of tract-tracing studies in humans has boosted advanced MRI techniques and multi-shell high-angular resolution diffusion MRI (MS-HARDI) has promised to shed more light on the structural connectivity of subcortical structures. Here, we estimated the possible dopaminergic innervation of the human thalamus via an MS-HARDI tractography of the SNc in healthy human young adults. Two MRI data sets were serially acquired using MS-HARDI schemes from ADNI and HCP neuroimaging initiatives in a group of 10 healthy human subjects (5 males, age range: 25–30 years). High resolution 3D-T1 images were independently acquired to individually segment the thalamus and the SNc. Starting from whole-brain probabilistic tractography, all streamlines through the SNc reaching the thalamus were counted, separately for each hemisphere, after excluding streamlines through the substantia nigra pars reticulata and all those reaching the basal ganglia, the cerebellum and the cortex. We found a reproducible structural connectivity between the SNc and the thalamus, with an average of ~12% of the total number of streamlines encompassing the SNc and terminating in the thalamus, with no other major subcortical or cortical structures involved. The first principal component map of dopamine receptor density from a normative PET image data set suggested similar dopamine levels across SNc and thalamus. This is the first quantitative report from in-vivo measurements in humans supporting the presence of a direct nigro-thalamic dopaminergic projection. While histological validation and concurrent PET-MRI remains needed for ultimate proofing of existence, given the potential role of this pathway, the possibility to achieve a good reproducibility of these measurements in humans might enable the monitoring of dopaminergic-related disorders, towards targeted personalized therapies. [ABSTRACT FROM AUTHOR]

Objective: To investigate differences in the microstructure of the spinothalamic tract (STT) white matter in people with chronic neck and shoulder pain (CNSP) using diffusion tensor imaging, and to assess its correlation with pain intensity and duration of the pain. Materials and methods: A 3.0T MRI scanner was used to perform diffusion tensor imaging scans on 31 people with CNSP and 24 healthy controls (HCs), employing the Automatic Fiber Segmentation and Quantification (AFQ) method to extract the STT and quantitatively analyze the fractional anisotropy (FA) and mean diffusivity (MD), reflecting the microstructural integrity of nerve fibers. Correlations of these differences with duration of pain and visual analog scale (VAS) scores were analyzed. Results: No significant differences in the mean FA or MD values of the bilateral STT were observed between people with CNSP and HCs (p > 0.05), as indicated by the two-sample t test. Further point-by-point comparison along 100 equidistant nodes within the STT pathway revealed significant reductions in FA values in the left (segments 12–18, 81–89) and right (segments 9–19, 76–80) STT in the CNSP group compared to HCs; significant increases in MD values were observed in the left (segments 1–13, 26–30, 71–91) and right (segments 8–17, 76–91) STT (p < 0.05, FWE corrected). Partial correlation analysis indicates that in people with CNSP, the FA values of the STT in regions with damaged white matter structure show a negative correlation with VAS scores and duration of pain, whereas MD values show a positive correlation with VAS scores and duration of pain. Conclusion: This study found that people with CNSP exhibit white matter microstructural abnormalities in the specific segments of STT. These abnormalities are associated with the patient's pain intensity and disease duration. The findings offer a new neuroimaging perspective on the pathophysiological basis of chronic pain in the ascending conduction process and its potential role in developing targeted intervention strategies. However, due to the limited sample size and the lack of statistical significance when analyzing the entire spinothalamic tract, these conclusions should be interpreted with caution. Further research with larger cohorts is necessary to validate these results. [ABSTRACT FROM AUTHOR]

The suicide rate for United States military veterans is 1.5× higher than that of non-veterans. To meaningfully advance suicide prevention efforts, research is needed to delineate factors that differentiate veterans with suicide attempt/s, particularly in high-risk groups, e.g., major depressive disorder (MDD), from those with suicidal ideation (no history of attempt/s). The current study aimed to identify clinical, neurocognitive, and neuroimaging variables that differentiate suicide-severity groups in veterans with MDD. Sixty-eight veterans with a DSM-5 diagnosis of MDD, including those with no ideation or suicide attempt (N = 21; MDD-SI/SA), ideation-only (N = 17; MDD + SI), and one-or-more suicide attempts (N = 30; MDD + SA; aborted, interrupted, actual attempts), participated in this study. Participants underwent a structured diagnostic interview, neurocognitive assessment, and 3 T-structural/diffusion tensor magnetic-resonance-imaging (MRI). Multinomial logistic regression models were conducted to identify variables that differentiated groups with respect to the severity of suicidal behavior. Relative to veterans with MDD-SI/SA, those with MDD + SA had significantly higher left cingulum fractional anisotropy, decreased attentional control on emotional-Stroop, and faster response time with intact accuracy on Go/No-Go. Relative to MDD + SI, MDD + SA had higher left cingulum fractional anisotropy and faster response time with intact accuracy on Go/No-Go. Findings are based on retrospective, cross-sectional data and cannot identify causal relationships. Also, a healthy control group was not included given the study's focus on differentiating suicide profiles in MDD. This study suggests that MRI and neurocognition differentiate veterans with MDD along the suicide-risk spectrum and could inform suicide-risk stratification and prevention efforts in veterans and other vulnerable populations. • Depressed veterans with history of suicide attempt exhibit cingulum alterations. • Attentional control skills help differentiate suicide-severity in depressed veterans. • Attentional control skills with suicide-specific information relates to suicidality. • MRI and neurocognition differentiate depressed veterans on the suicide-risk spectrum. [ABSTRACT FROM AUTHOR]

Hearing loss is considered a potentially modifiable risk factor for dementia. The sensory deprivation theory postulates that hearing loss adversely affects cognition in older adults through structural brain changes, but longitudinal studies are scarce. To find evidence for a possible detrimental effect of hearing loss on white matter microstructure, we carried out a longitudinal study in the population-based Rotterdam Study. A total of 1877 participants with a median age at baseline of 56.4 years (IQR: [52.2–60.0]) underwent audiometry and had longitudinal diffusion imaging data available with a mean follow-up of 4.0 years. A lower level of hearing acuity was associated with worse white matter microstructure in the left uncinate fasciculus and superior longitudinal fasciculus at baseline. Poorer hearing acuity was also associated with faster microstructural deterioration over time in the left superior longitudinal fasciculus. The strongest effects were observed for low-frequency hearing thresholds, while the high-frequency thresholds showed the weakest associations. These results suggest that hearing loss may contribute to the age-related decline in brain structure, consistent with the sensory deprivation theory. • Hearing loss has tract-specific rather than widespread effects on white matter. • Most pronounced effects are found in the superior longitudinal fasciculus. • Strength of associations varies across hearing threshold frequency range. • Addition of non-linear age effects better removes age confounding. [ABSTRACT FROM AUTHOR]

Background: PD is marked by both motor and non-motor symptoms, with its pathophysiology involving many neural pathways and brain regions beyond the dopaminergic system. While mainly gray matter changes have been noted, white matter changes also exist in PD. Habenula, known for its role in reward processing, mood regulation, motor functions, and cognition, is of interest due to its connection to mood disorders in PD. This study aims to explore diffusion metrics and structural connectivity changes in the habenula of newly diagnosed PD patients using 7 T MRI. Methods: 84 PDs and 38 HCs were recruited from Maastricht University Medical Centre. Clinical, demographic, and total Beck Depression Inventory (BDI) scores were recorded. A 7 T brain MRI was conducted. Diffusion metrics and structural connectivity were evaluated. Results: The mean diffusion metrics of Hb were not significantly different between the groups. However, in PD patients, there was an increase in mean structural connectivity from the right Hb to the right hippocampus (p = 0.006) and the right fusiform gyrus (p = 0.007). On the left side, enhanced connectivity was observed with the left pallidum (p = 0.040) and left accumbens (p = 0.009). In the PD group, a significant correlation was found between the BDI total score and increased structural connectivity from the right Hb to the left cingulate isthmus (R2 = 0.090, p = 0.003). Conclusion: This pioneering study examines diffusion metrics and structural connectivity of Hb in PD patients using high-resolution 7 T MRI. Our findings highlight the habenula's potential role in PD pathophysiology, with altered connectivity suggesting early neurodegenerative or compensatory processes. These results underscore the importance of the habenula as a biomarker for PD and its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

Purpose: The goal of glioma surgery is maximal tumor resection associated with minimal post-operative morbidity. Diffusion tensor imaging-tractography/fiber tracking (DTI-FT) is a valuable white-matter (WM) visualization tool for diagnosis and surgical planning. Still, it assumes a descriptive role since the main DTI metrics and parameters showed several limitations in clinical use. New applications and quantitative measurements were recently applied to describe WM architecture that surround the tumor area. The brain adjacent tumor area (BAT) is defined as the region adjacent to the gross tumor volume, which contains signal abnormalities on T2-weighted or FLAIR sequences. The DTI-FT analysis of the BAT can be adopted as predictive values and a guide for safe tumor resection. Methods: This is an observational prospective study on an extensive series of glioma patients who performed magnetic resonance imaging (MRI) with pre-operative DTI-FT analyzed on the BAT by two different software. We examined DTI parameters of Fractional anisotropy (FA mean, min-max), Mean diffusivity (MD), and the shape-metric "tract irregularity" (TI) grade, comparing it with the surgical series' clinical, radiological, and outcome data. Results: The population consisted of 118 patients, with a mean age of 60.6 years. 82 patients suffering from high-grade gliomas (69.5%), and 36 from low-grade gliomas (30.5%). A significant inverse relationship exists between the FA mean value and grading (p = 0.001). The relationship appears directly proportional regarding MD values (p = 0.003) and TI values (p = 0.005). FA mean and MD values are susceptible to significant variations with tumor and edema volume (p = 0.05). TI showed an independent relationship with grading regardless of tumor radiological features and dimensions, with a direct relationship with grading, ki67% (p = 0,05), PFS (p < 0.001), and EOR (p < 0.01). Conclusion: FA, MD, and TI are useful predictive measures of the clinical behavior of glioma, and TI could be helpful for tumor grading identification and surgical planning. [ABSTRACT FROM AUTHOR]

Purpose: To compare postmortem in situ with ex situ MRI parameters, including volumetry, diffusion tensor imaging (DTI), and relaxometry for assessing methodology‐induced alterations, which is a crucial prerequisite when performing MRI biomarker validation. Methods: MRI whole‐brain scans of five deceased patients with amyotrophic lateral sclerosis were performed at 3 T. In situ scans were conducted within 32 h after death (SD 18 h), and ex situ scans after brain extraction and 3 months of formalin fixation. The imaging protocol included MP2RAGE, DTI, and multi‐contrast spin‐echo and multi‐echo gradient‐echo sequences. Volumetry, fractional anisotropy, mean diffusivity, T1, T2, and T2*$$ {T}_2^{\ast } $$ have been assessed for specific brain regions. Results: When comparing ex situ to in situ values, the following results were obtained. Deep gray matter as well as the thalamus and the hippocampus showed a reduced volume. Fractional anisotropy was reduced in the cortex and the whole brain. Mean diffusivity was decreased in white matter and deep gray matter. T1 and T2 were reduced in all investigated structures, whereas T2*$$ {T}_2^{\ast } $$ was increased in the cortex. Conclusion: The results of this study show that the volumes and MRI parameters of several brain regions are potentially affected by tissue extraction and subsequent formalin fixation, suggesting that methodological alterations are present in ex situ MRI. To avoid overlap of indistinguishable methodological and disease‐related changes, we recommend performing in situ postmortem MRI as an additional intermediate step for in vivo MRI biomarker validation. [ABSTRACT FROM AUTHOR]

Background: It is difficult to distinguish between tumor progression (TP) and treatment-related abnormalities (TRA) in treated glioblastoma patients via conventional MRI, but this distinction is crucial for treatment decision making. Glioblastoma is known to exhibit an invasive growth pattern along white matter architecture and vasculature. This study quantified lesion development patterns in treated glioblastoma lesions and their relation to white matter microstructure to distinguish TP from TRA. Materials and methods: Glioblastoma patients with confirmed TP or TRA with T1-weighted contrast-enhanced and DTI MR scans from two posttreatment follow-up timepoints were reviewed. The contrast-enhancing regions were segmented, and the regions were coregistered to the DTI data. Lesion increase vectors were categorized into two groups: parallel (0–20 degrees) and perpendicular (70–90 degrees) to white matter. FA-values were also extracted. To test for a statistically significant difference between the TP and TRA groups, a Mann‒Whitney U test was performed. Results: Of 73 glioblastoma patients, fifteen were diagnosed with TRA, whereas 58 patients suffered TP. TP had a 25.8% (95% CI 24.1%-27.6%) increase in parallel lesions, and TRA had a 25.4% (95% CI 20.9%-29.9%) increase in parallel lesions. The perpendicular increase was 14.7% for TP (95% CI 13.0%-16.4%) and 18.0% (95% CI 13.5%-22.5%) for TRA. These results were not significantly different (p = 0.978). FA value for TP showed to be 0.248 (SD = 0.054) and for TRA it was 0.231 (SD = 0.075), showing no statistically significant difference (p = 0.121). Conclusions: Based on our results, quantifying posttreatment contrast-enhancing lesion development directionality with DTI in glioblastoma patients does not appear to effectively distinguish between TP and TRA. [ABSTRACT FROM AUTHOR]

Multiple neurocognitive processes are involved in the highly complex task of producing written words. Yet, little is known about the neural pathways that support spelling in healthy adults. We assessed the associations between performance on a difficult spelling-to-dictation task and microstructural properties of language-related white matter pathways, in a sample of 73 native English-speaking neurotypical adults. Participants completed a diffusion magnetic resonance imaging scan and a cognitive assessment battery. Using constrained spherical deconvolution modeling and probabilistic tractography, we reconstructed dorsal and ventral white matter tracts of interest, bilaterally, in individual participants. Spelling associations were found in both dorsal and ventral stream pathways. In high-performing spellers, spelling scores significantly correlated with fractional anisotropy (FA) within the left inferior longitudinal fasciculus, a ventral stream pathway. In low-performing spellers, spelling scores significantly correlated with FA within the third branch of the right superior longitudinal fasciculus, a dorsal pathway. An automated analysis of spelling errors revealed that high- and low- performing spellers also differed in their error patterns, diverging primarily in terms of the orthographic distance between their errors and the correct spelling, compared to the phonological plausibility of their spelling responses. The results demonstrate the complexity of the neurocognitive architecture of spelling. The distinct white matter associations and error patterns detected in low- and high- performing spellers suggest that they rely on different cognitive processes, such that high-performing spellers rely more on lexical-orthographic representations, while low-performing spellers rely more on phoneme-to-grapheme conversion. [ABSTRACT FROM AUTHOR]

Objective: Cognitive deficits in mild traumatic brain injury (mTBI) can persist over three months, and symptomatic patients may not be readily diagnosed. Although diffusion tensor imaging (DTI) can detect microstructural white matter tract (WMT) changes in mTBI, the underlying recovery process is not fully understood. We aimed to investigate WMT changes at 3 months post-mTBI between cognitively recovered (REC) and non-recovered (NREC) mTBI subjects using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). Methods: Fifty-seven mTBI subjects were divided into REC (n=16) and NREC (n=41) groups. Ten healthy controls (HC) were recruited. MRI and Neuropsychological Assessment Battery-Screening Module (S-NAB) performance were assessed at baseline and three months before subjects were classified as REC and NREC. DTI and NODDI parameters of 50 ROIs corresponding to WMTs were compared between REC, NREC and HC. Results: NODDI detected more significant changes (p<0.05) in multiple ROIs than DTI. Lower Neurite Density Index (NDI) was demonstrated in REC versus NREC at multiple ROIs. Increased Orientation Dispersion Index (ODI) and decreased Isotropic Volume Fraction (ISOVF) were detected at several WMTs in both groups. Conclusion: Reduced NDI in the overall mTBI cohort suggests axonal degeneration post-trauma. We postulate that at three months' timeline, there is a combination of axonal degeneration and astrogliosis, which is more extensive in NREC than REC. [ABSTRACT FROM AUTHOR]

Diffusion MRI was introduced in 1985, showing how the diffusive motion of molecules, especially water, could be spatially encoded with MRI to produce images revealing the underlying structure of biologic tissues at a microscopic scale. Diffusion is one of several Intravoxel Incoherent Motions (IVIM) accessible to MRI together with blood microcirculation. Diffusion imaging first revolutionized the management of acute cerebral ischemia by allowing diagnosis at an acute stage when therapies can still work, saving the outcomes of many patients. Since then, the field of diffusion imaging has expanded to the whole body, with broad applications in both clinical and research settings, providing insights into tissue integrity, structural and functional abnormalities from the hindered diffusive movement of water molecules in tissues. Diffusion imaging is particularly used to manage many neurologic disorders and in oncology for detecting and classifying cancer lesions, as well as monitoring treatment response at an early stage. The second major impact of diffusion imaging concerns the wiring of the brain (Diffusion Tensor Imaging, DTI), allowing to obtain from the anisotropic movement of water molecules in the brain white-matter images in 3 dimensions of the brain connections making up the Connectome. DTI has opened up new avenues of clinical diagnosis and research to investigate brain diseases, neurogenesis and aging, with a rapidly extending field of application in psychiatry, revealing how mental illnesses could be seen as Connectome spacetime disorders. Adding that water diffusion is closely associated to neuronal activity, as shown from diffusion fMRI, one may consider that diffusion MRI is ideally suited to investigate both brain structure and function. This article retraces the early days and milestones of diffusion MRI which spawned over 40 years, showing how diffusion MRI emerged and expanded in the research and clinical fields, up to become a pillar of modern clinical imaging. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adult patients with mild traumatic brain injury (mTBI) exhibit distinct phenotypes of emotional and cognitive functioning identified by latent profile analysis of clinical neuropsychological assessments. When discerned early after injury, these latent clinical profiles have been found to improve prediction of long-term outcomes from mTBI. The present study hypothesized that white matter (WM) microstructure is better preserved in an emotionally resilient mTBI phenotype compared with a neuropsychiatrically distressed mTBI phenotype. METHODS: The present study used diffusion magnetic resonance imaging to investigate and compare WM microstructure in major association, projection, and commissural tracts between the two phenotypes and over time. Diffusion magnetic resonance images from 172 patients with mTBI were analyzed to compute individual diffusion tensor imaging maps at 2 weeks and 6 months after injury. RESULTS: By comparing the diffusion tensor imaging parameters between the two phenotypes at global, regional, and voxel levels, emotionally resilient patients were shown to have higher axial diffusivity compared with neuropsychiatrically distressed patients early after mTBI. Longitudinal analysis revealed greater compromise of WM microstructure in neuropsychiatrically distressed patients, with greater decrease of global axial diffusivity and more widespread decrease of regional axial diffusivity during the first 6 months after injury compared with emotionally resilient patients. CONCLUSIONS: These results provide neuroimaging evidence of WM microstructural differences underpinning mTBI phenotypes identified from neuropsychological assessments and show differing longitudinal trajectories of these biological effects. These findings suggest that diffusion magnetic resonance imaging can provide short- and long-term imaging biomarkers of resilience.

BACKGROUND: Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging such as diffusion MRI (dMRI). Since SOR involves hypersensitivity to external stimuli, we test the hypothesis that children with SOR require compensatory neuroplasticity in the form of superior WM microstructural integrity to protect against internalizing behavior, leaving those with impaired WM microstructure vulnerable to somatization and depression. METHODS: Children ages 8-12 years old with neurodevelopmental concerns were assessed for SOR using a comprehensive structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment, and underwent 3 Tesla MRI with multishell multiband dMRI. Tract-based spatial statistics was used to measure diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics from global WM and nineteen selected WM tracts. Correlations of DTI and NODDI measures with measures of somatization and emotional disturbance from the Behavioral Assessment System for Children, 3rd edition (BASC-3), were computed in the SOR group and in matched children with neurodevelopmental concerns but not SOR. RESULTS: Global WM fractional anisotropy (FA) is negatively correlated with somatization and with emotional disturbance in the SOR group but not the non-SOR group. Also observed in children with SOR are positive correlations of radial diffusivity (RD) and free water fraction (FISO) with somatization and, in most cases, emotional disturbance. These effects are significant in boys with SOR, whereas the study is underpowered for girls. The most affected white matter are medial lemniscus and internal capsule sensory tracts, although effects of SOR are observed in many cerebral, cerebellar, and brainstem tracts. CONCLUSION: White matter microstructure is related to affective behavior in children with SOR.

PHN is one of the most common clinical complications of herpes zoster (HZ), the pathogenesis of which is unclear and poorly treated clinically, and many studies now suggest that postherpetic neuralgia (PHN) pain may be related to central neurologic mechanisms. This study aimed to investigate the white matter structural networks and changes in the organization of the rich-club in HZ and PHN. Diffusion imaging (DTI) data from 89 PHN patients, 76 HZ patients, and 66 healthy controls (HCs) were used to construct corresponding structural networks. Using graph-theoretic analysis, changes in the overall and local characteristics of the structural networks and rich-club organization were analyzed, and their correlations with clinical scales were analyzed. Compared with HCs, PHN patients had reduced global efficiency (Eg), reduced local efficiency (Eloc), a reduced clustering coefficient (Cp), a longer characteristic path length (Lp), and reduced nodal efficiency (Ne) in several brain regions, including the right posterior cingulate gyrus, the right supraoccipital gyrus, the bilateral postcentral gyrus, and the right precuneus; HZ patients had reduced Eg, a longer Lp, and reduced right orbital frontalis suprachiasmatic Ne. Moreover, HZ and PHN patients showed a significant reduction in the strength of rich-club connections. Compared with HZ patients, the intensities of the rich-club and feeder connections were lower in the PHN patients. Moreover, the changes in the structural networks and rich-club organization topology indices of the patients in the HZ and PHN patients were significantly correlated with disease duration, pain scores, and emotional changes. The structural networks of HZ and PHN patients exhibited reduced network transmission efficiency and rich-club connectivity, possibly due to structural damage to the white matter, and this was more obvious in PHN patients. The rich-club connectivity of HZ patients showed incomplete compensation in the acute pain stage. [ABSTRACT FROM AUTHOR]

Abstract Background Synaptic degeneration, axonal injury, and white matter disintegration are among the pathological events in Alzheimer’s disease (AD), for which growth-associated protein 43 (GAP-43) and diffusion tensor imaging (DTI) could be an indicator. In this study, the cerebrospinal fluid (CSF) GAP-43 clinical trajectories and their association with progression and AD hallmarks with white matter microstructural changes were evaluated. Methods A total number of 133 participants were enrolled in GAP-43 and DTI values were compared between groups, both cross-sectionally and longitudinally with two and four-year follow-ups. Subsequently, the correlation between GAP-43 levels in the CSF and DTI values was investigated using Spearman’s correlation. Results The CSF level of GAP-43 is negatively correlated with the mean diffusivity measures in Fornix (Cres)/Stria terminals in early and late MCI (rs=-0.478 p = 0.021 and rs=-0.425 p = 0.038). Additionally, the CSF level of GAP-43 is negatively correlated with fractional anisotropy in the cingulum in late MCI (rs=-0.437 p = 0.033). Moreover, the axial diffusivity in superior corona radiate (rs=-0.562 p = 0.005 and rs=-0.484 p = 0.036) and radial diffusivity in superior fronto-occipital fasciculus was negatively correlated with GAP-43 level in the early and mid-MCI participants (rs=-0.520 p = 0.011 and rs=-0.498 p = 0.030). Conclusions Presynaptic marker GAP-43 in combination with DTI can be used as a novel biomarker to identify microstructural synaptic degeneration in the early MCI. In addition, it can be used as a biomarker for tracking the progression of AD and monitoring treatment efficacy.

Background: Diffuse astrocytomas preferentially infiltrate eloquent areas affecting the outcome. A preoperative understanding of isocitrate dehydrogenase (IDH) status may offer opportunities for specific targeted therapies impacting treatment management. The aim of this study was to analyze clinical, topographical, radiological in WHO 2 astrocytomas with different IDH status and the long-term patient’s outcome. Methods: A series of confirmed WHO 2 astrocytoma patients (between 2005 and 2015) were retrospectively analyzed. MRI sequences (FLAIR) were used for tumor volume segmentation and to create a frequency map of their locations into the Montreal Neurological Institute (MNI) space. The Brain-Grid (BG) system (standardized radiological tool of intersected lines according to anatomical landmarks) was used as an overlay for infiltration analysis of each tumor. Long-term follow-up was used to perform a survival analysis. Results: Forty patients with confirmed IDH status (26 IDH-mutant, IDHm/14 IDH-wild type, IDHwt) according to WHO 2021 classification were included with a mean follow-up of 7.8 years. IDHm astrocytomas displayed a lower number of BG-voxels (P < 0.05) and were preferentially located in the anterior insular region. IDHwt group displayed a posterior insular and peritrigonal location. IDHwt group displayed a shorter OS compared with IDHm (P < 0.05), with the infiltration of 7 or more BG-voxels as an independent factor predicting a shorter OS. Conclusions: IDHm and IDHwt astrocytomas differed in preferential location, number of BG-voxels and OS at long follow-up time. The number of BG-voxels affected the OS in IDHwt was possibly reflecting higher tumor invasiveness. We encourage the systematic use of alternative observational tools, such as gradient maps and the Brain-Grid analysis, to better detect differences of tumor invasiveness in diffuse low-grade gliomas subtypes.

Background: Brain structure changes after long-term adaptation to the high-altitude environment; however, related studies are few, results are in consistent, and long-term effects on cognitive function and pathophysiological mechanisms are unclear. Therefore, diffusion tensor imaging (DTI) was used to investigate the damage to white matter fiber tracts and correlations between brain structural abnormalities and cognitive function. Methods: Forty healthy Han people living on the high-altitude and 40 healthy Han people living on the plains were enrolled in this study and underwent magnetic resonance imaging, emotional state assessment, and cognitive function tests. The sex, age, education level, and social status of the two groups were not different. The tract-based spatial statistics (TBSS) method was used to analyze the DTI parameters of the white matter fiber tracts of the two groups. Moreover, the partial correlation method (age and sex as covariates) was used to analyze the correlations between the intergroup differences in the DTI parameters and a series of clinical indicators of emotional state and cognitive function. Two-sample t tests, Mann-Whitney U test, generalized linear model, or chi-square tests were used for statistical analysis. Results: Compared with those individuals in the plain group, the scores on the PSQI, SDS, SAS, PHQ-9, and GAD-7 of individuals in the high-altitude group were higher, while the scores on the DST-Backwards, MoCA, and MMSE in the high-altitude group were lower. The fractional anisotropy (FA) value of the body of the corpus callosum in the high-altitude group was lower than that in the plain group. The FA value of the body of the corpus callosum in the plain group was negatively correlated with the Logical Memory, while no significant correlation was found in the high-altitude group. Conclusion: This study revealed that long-term exposure to a high-altitude environment could lead to a series of changes in sleep, emotion, and cognitive function and irreversible damage to the white matter microstructure of the body of the corpus callosum, which is the related brain region responsible for logical memory. The absence of logical memory impairment in the healthy Han Chinese population living on the high-altitude in this study may be due to the existence of adaptive compensation after long-term high-altitude exposure. [ABSTRACT FROM AUTHOR]

It is known that abnormal functional connectivity (FC) in schizophrenia (SZ) is closely related to structural connectivity (SC). We speculate that indirect SC also have an impact on FC in SZ patients. Conventional single-layer network has limitations for studying the relationship between indirect SC and FC. Thus, this study constructed a multiplex network based on structural connectivity and functional connectivity (SC-FC). The SC-FC bandwidth and SC-FC cost are used to analyze the impact of indirect SC on FC. Moreover, this paper proposed mediation ability, mediation cost, mediated strength and mediated cost to quantify the effects of mediator nodes and mediated nodes on indirect SC. The results show that SZ patients exhibit lower SC-FC bandwidth and SC-FC cost compared to healthy controls (HC), which could be caused by the limbic and subcortical network (LSN), default mode network (DMN) and visual network (VN). The mediator and mediated nodes in indirect SC of SZ patients also showed diminished effects. These findings suggest that functional communication ability and cost in SZ patients are influenced by indirect SC. This study provides new perspectives for understanding the relationship between indirect SC and FC, and provides strong evidence for interpreting the physiological mechanisms of SZ patients. • Construction of multiplex network based on structural connectivity (SC) and functional connectivity (FC). • Using SC-FC bandwidth and SC-FC cost to analyze how indirect SC affects FC. • The SC-FC bandwidth and SC-FC cost of SZ patients were significantly reduced at whole-brain and module levels. • The role of nodes in affecting FC was quantified from mediator and mediated perspectives. • Results suggest that indirect SC in SZ patients results in reduced functional communication ability and cost. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether individuals with subjective cognitive decline (SCD) have changes in whole-brain network characteristics and intracerebral node characteristics in the structural network, and whether there is a difference between SCD with and without Apolipoprotein E4 (APOEε4). Methods: This cross-sectional study included 36 individuals without SCD without APOEε4 (healthy control, HC group), 21 individuals with SCD with APOEε4 (APOEε4+ group), and 33 individuals with SCD without APOEε4 (APOEε4-group). The white matter structural network was constructed using the fractional anisotropy (FA) based deterministic fiber tracking method. Graph theory was used to analyze the whole-brain network characteristics and intracerebral node characteristics of the three groups. Results: Regarding the whole-brain network characteristics, all three groups exhibited small-worldness in their structural networks. The clustering coefficient (Cp) and local efficiency (Eloc) in the APOEε4+ and APOEε4- groups were significantly lower than in the HC group (p < 0.05), but no significant difference in Cp or Eloc was observed between the APOEε4+ and APOEε4- groups. Regarding intracerebral node characteristics, there were significant differences in some brain regions, mainly the default mode network (DMN), the occipital lobe, the temporal lobe, and subcortical regions. The change in intracerebral node characteristics was different between the APOEε4+ group and the APOEε4- group. Conclusions: Individuals with SCD demonstrate changes in whole-brain network characteristics and intracerebral node characteristics in the structural network. Moreover, differences exist between APOEε4+ and APOEε4- individuals. [ABSTRACT FROM AUTHOR]

Neurological disease due to single-gene defects represents a targetable entity for adeno-associated virus (AAV)-mediated gene therapy. The delivery of AAV-mediated gene therapy to the brain is challenging, owing to the presence of the blood–brain barrier. Techniques in gene transfer, such as convection-enhanced intraparenchymal delivery and image-guided delivery to the cerebrospinal fluid spaces of the brain, have led the field into highly accurate delivery techniques, which provide correction of genetic defects in specific brain regions or more broadly. These techniques commonly use magnetic resonance imaging (MRI), computed tomography, and fluoroscopic guidance. Even more, the neuroimaging changes evaluated by MRI, MR spectroscopy, diffusion tensor imaging, and functional MRI can serve as important biomarkers of therapy effect and overall disease progression. Here, we discuss the role of neuroimaging in delivering AAV vectors and monitoring the effect of gene therapy. [ABSTRACT FROM AUTHOR]

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Diffusion magnetic resonance imaging (MRI) has been utilized to probe the renal microstructures but investigating the three-dimensional (3D) tubular network still presents significant challenges due to the complicated architecture of kidney. This study aims to assess whether high angular resolution diffusion imaging (HARDI) could improve the reconstruction of 3D tubular architectures. Kidneys from both mice and rats were imaged using 3D diffusion-weighted pulse sequences at 9.4 T. Five healthy mouse kidneys were scanned at an isotropic spatial resolution of 40 mm, with a b value of 1500 s/ mm2 across 46 diffusion encoding directions. The study employed diffusion tensor imaging (DTI) and generalized Q-sampling imaging (GQI) to examine the tubular orientation distributions and tractography, validated by conventional histology. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified and compared among the inner medullar (IM), outer medullar (OM), and cortex (CO) at different angular resolutions. FA values, estimated with 6 diffusion-weighted images (DWIs), were significantly overestimated by 49.9% (p < 0.001) in IM, 179.4% (p < 0.001) in OM, and 225.5% (p < 0.001) in CO, compared to using 46 DWIs. In contrast, MD exhibited less variations to angular resolution variations (3.4% in IM, 4.2% in OM, and 4.6% in CO). Both DTI and GQI at high angular resolution successfully traced renal tubular structures throughout the kidney, with GQI demonstrating superior performance in generating more continuous tracts. Furthermore, disrupted renal tubule structures were observed in a chronic kidney disease (CKD) rat model. HARDI, especially when combined with the GQI approach, holds promise in tracking complicated 3D tubule architectures and may serve as a potent tool for kidney disease research. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (CSVD) is a syndrome of pathology, imaging, and clinical manifestations caused primarily by a variety of functional or structural lesions in the small blood vessels of the brain. CSVD contributes to approximately 45% of dementia and 25% of ischemic strokes worldwide and is one of the most important causes of disability. The disease progresses insidiously, and patients often have no typical symptoms in the early stages, but have an increased risk of stroke, death, and poor long-term prognosis. Therefore, early diagnosis of CSVD is particularly important. Neuroimaging is the most important diagnostic tool used for CSVD. Therefore, it is important to explore the imaging mechanisms of CSVD for its early diagnosis and precise treatment. In this article, we review the principles and analysis methods of DTI, analyze the latest DTI studies on CSVD, clarify the disease-lesion mapping relationships between cerebral white matter (WM) microstructural damage and CSVD, explore the pathogenic mechanisms and preclinical imaging features of CSVD, and summarize the latest research directions of CSVD and research methods to provide a comprehensive and objective imaging basis for the diagnosis and treatment of CSVD. [ABSTRACT FROM AUTHOR]

Background: Synaptic degeneration, axonal injury, and white matter disintegration are among the pathological events in Alzheimer's disease (AD), for which growth-associated protein 43 (GAP-43) and diffusion tensor imaging (DTI) could be an indicator. In this study, the cerebrospinal fluid (CSF) GAP-43 clinical trajectories and their association with progression and AD hallmarks with white matter microstructural changes were evaluated. Methods: A total number of 133 participants were enrolled in GAP-43 and DTI values were compared between groups, both cross-sectionally and longitudinally with two and four-year follow-ups. Subsequently, the correlation between GAP-43 levels in the CSF and DTI values was investigated using Spearman's correlation. Results: The CSF level of GAP-43 is negatively correlated with the mean diffusivity measures in Fornix (Cres)/Stria terminals in early and late MCI (rs=-0.478 p = 0.021 and rs=-0.425 p = 0.038). Additionally, the CSF level of GAP-43 is negatively correlated with fractional anisotropy in the cingulum in late MCI (rs=-0.437 p = 0.033). Moreover, the axial diffusivity in superior corona radiate (rs=-0.562 p = 0.005 and rs=-0.484 p = 0.036) and radial diffusivity in superior fronto-occipital fasciculus was negatively correlated with GAP-43 level in the early and mid-MCI participants (rs=-0.520 p = 0.011 and rs=-0.498 p = 0.030). Conclusions: Presynaptic marker GAP-43 in combination with DTI can be used as a novel biomarker to identify microstructural synaptic degeneration in the early MCI. In addition, it can be used as a biomarker for tracking the progression of AD and monitoring treatment efficacy. [ABSTRACT FROM AUTHOR]