Internal Capsule Research Articles

Abstract TMP77: Robotic-Guided Implantation of 3D-Printed Hydrogel Scaffolds to Enhance Axonal Regeneration and Functional Recovery After Stroke: A Novel Minimally Invasive Surgical Approach

Ischemic strokes often disrupt white matter (WM) microstructure, particularly affecting the corticospinal tract (CST) in the internal capsule (IC), leading to significant motor deficits. While evidence shows that axon sprouting occurs post-stroke, it often follows erratic paths, limiting functional recovery. Recent advances in 3D-printed hydrogel scaffolds have shown promise in guiding axon regeneration in spinal cord injury models. We hypothesize that implanting these scaffolds at white matter sites affected by stroke, aligned with CST fibers, will enhance functional axonal regeneration and motor recovery. Our aim is to develop and validate a precise and clinically applicable scaffold delivery system for future human studies. We have developed a novel, minimally invasive stereotaxic method for the precise deployment of 1.3 mm diameter scaffolds within the IC of non-human primates (NHPs). Our approach utilizes a clinically available stereotactic robot (ROSA, ZimmerBiomet) combined with a linear cannula system (AlphaOmega) to plan scaffold placement. Then, we attempted to deploy scaffolds devices into thermally coagulated lesions in NHPs (n=2) and simulated lesions within hydrogel phantoms (n=2). Post-implant MRI, co-registered with high-resolution diffusion tensor imaging were applied to check for scaffold placement accuracy (n=4). We further complement the scaffold placement method by using a novel neurosurgical microrobot (Robeauté) designed for navigation along 3D nonlinear curves, with accuracy confirmed by CBCT imaging in phantom tests. Our implantation methods accurately placed scaffolds in the intended locations and orientations, aligning with CST fibers in both phantom models and NHP brains. The deviation angle between the scaffold and CST fibers was 17.83° (SD 6.71°, n=3). The scaffolds were precisely positioned within the IC, validating our approach. Our robot-guided method accurately steered them to their intended position, demonstrating minimal errors in targeted white matter regions. The methods described are poised for clinical translation, potentially extending the applicability of scaffold technology for improving motor function post-stroke. We are preparing NHPs for behavioral and upper limb motor assessments to evaluate the impact of scaffold implantation on axon regeneration, recovery, and performance. This research aims to enhance our understanding of ischemic stroke and develop innovative therapies to restore motor function in patients.

Abstract 34: White Matter Alteration after Stroke Is Correlated with Neuroinflammation: A Combined Fixel-based Diffusion MRI Analysis and 18F-THK-5351 PET Study

Introduction: Neuroinflammation plays a major role in post-stroke neuronal injury. Previous studies applied 18F-THK-5351 tau PET to identify the existence of neuroinflammation after infarction. Meanwhile, post-stroke microstructural degradation of white matter (WM) fibers can be observed using fixel-based analysis (FBA) of diffusion MRI (dMRI). We integrate 18F-THK-5351 tau PET and FBA-dMRI in ischemic stroke patients to investigate the relationship between poststroke neuroinflammation process and WM fiber alterations. Methods: 33 patients with lacunar infarcts received 18F-THK-5351 PET and dMRI (Siemens Biograph mMR PET-MR 3 Tesla scanner) at 3 months poststroke. 27 age-matched healthy controls were recruited. The reference region of 18F-THK-5351 PET was set at cerebellar cortex. FBA-dMRI metrics included microstructural fiber density (FD), fiber cross-section (FC, macrostructural morphometry), and combined-FD/FC (FDC, the overall fiber bundle connectivity). Clinical severity assessments included infarction volume, NIHSS, BI, and mRS. The whole-brain fixel-wise statistical analysis used the general linear model. Correlation anlaysis was for FBA metrics and clinical severity. Non-parametric testing >5000 permutations was used for multiple comparisons, p <0.05 using a strong family-wise error control as statistical significance. Results: All patients had lacunar infarcts at internal capsule, including 19 left and 14 right lacunes. The mean age was 64.9±7.7 in patients v.s. 61.3±9.4 in controls ( p =0.47). FBA-dMRI showed significant reductions in FD, FC, and FDC at corticospinal tract in patients compared to the controls. Tau PET demonstrated the highest uptake of 18F-THK-5351 at ischemia core. The spatial patterns of 18F-THK-5351 retention were highly consistent with the fixel metrics reduction distributions (Figure 1). Infarct volumes and clinical severity significantly negatively correlated with the fixel measures in patients. Larger infarct volume or more severity corresponds to lower FBA value (Figure 2). Conclusions: Integrating 18F-THK-5351 PET and FBA-dMRI demonstrates fiber-specific WM reductions associated with the neuroinflammation process, showing consistent spatial patterns between neuroinflammation and WM degeneration in stroke patients. Tract-specific WM reductions correlated with infarct volume and functional outcomes 3 month poststroke. Our findings have implications for understanding the mechanisms underlying functional impairment after ischemic stroke.

P-918. Rabies encephalitis: Spectrum of MRI findings and predicted probability of abnormality detection based on symptom duration

Abstract Background Rabies is a highly lethal infectious disease and is equivalent to a death sentence for the patient. With currently available tests, the ante-mortem diagnostic sensitivity is only ∼40%. Currently, there are only isolated case reports or small case series exploring the MRI features in rabies encephalitis. T2 TSE showing hyperintensities in bilateral basal ganglia (caudate nucleus, putamen and globus pallidus) and thalamus and corresponding DWI and ADC images showing true diffusion restriction Methods A prospective observational study was designed to explore the patterns of MRI abnormalities in rabies patients. A total of 31 patients were enrolled in the study, out of which 21 underwent Contrast-Enhanced Magnetic Resonance Imaging of Brain and spinal cord. FLAIR/T2 images showing hyperintensities in dorsal brainstem, cervical spinal cord Results Overall, MRI was normal in 10(47.6%) patients, whereas 11(52.4%) patients showed abnormalities. Abnormalities were detected in various brain regions with brainstem, spinal cord and basal ganglia being the most commonly affected regions. Other regions such as the cortex, sub-cortical white matter, limbic system, internal capsule, corona radiata, thalamus, and sub-thalamic region were also involved to varying degrees. Diffusion-weighted-imaging showed typical pattern of diffusion restriction in 6 cases (28.5%). No gadolinium contrast enhancement was observed in any patient. Overall, no significant difference in neuroimaging findings were observed between encephalitic and paralytic forms of rabies. In addition, univariate logistic regression analysis revealed that the likelihood of detecting abnormalities on MRI increases with the duration from the symptom onset. T2 hyperintensity in conus medullaris with contrast enhancing cauda equina nerve roots Conclusion Till date this is the largest prospective study (21 cases) exploring the MRI findings in the patients of rabies encephalitis. The study demonstrated certain patterns of brain imaging in rabies which in the appropriate clinical context could significantly aid in establishing the ante-mortem diagnosis of rabies encephalitis. At the same time, the study also highlights the fact that a normal MRI brain does not rule out the diagnosis and that the probability of finding specific abnormalities on MRI increases as the disease progresses. Univariable logistic regression to estimate predicted probability of appearance of MRI abnormality after appearance of 1st cardinal symptom Disclosures All Authors: No reported disclosures

COMPUTED TOMOGRAPHY CEREBRAL PERFUSION TO PREDICT FUNCTIONAL OUTCOME IN PAEDIATRIC HEAD INJURY: A COMPARITIVE STUDY OF VOXEL BASED AND WHOLE BRAIN PERFUSION.

This study evaluates the extent of perfusion abnormalities in pediatric traumatic head injury patients by using computed tomography perfusion (CTP) and compares the efficacy of voxel based and whole brain perfusion data clinically with functional outcome scales GOSE-P and MRS. In this Prospective study 100 eligible patients of age group 0-15 years were enrolled. Subjects were categorized into mild, moderate and severe traumatic brain injury using GCS.CT perfusion scans were performed at admission and at time of discharge. Both voxel-based and whole brain perfusion data were acquired at five regions of interest: orbitofrontal cortex, internal capsule, thalamus, caudate nucleus, and sensorimotor cortex for cerebral blood perfusion. The extent of perfusion abnormalities were noted in CTP scans. GOSE-P and MRS were utilised to clinically evaluate functional outcomes. Significant differences in CT perfusion findings between voxel-based and whole brain approaches were noted. Voxel-based scans demonstrated superior predictive value in severe cases, while whole brain scans were promising in moderate cases. GCS scores and specific CT parameters (CBF AND MTT) were also significant predictors of outcomes. The comparative analysis highlights the complementary roles of voxel-based and whole brain perfusion CT in predicting functional outcomes in pediatric head injury cases. Clinicians should consider both approaches when evaluating cerebral perfusion status and making treatment decisions. Further research is warranted to validate these findings and refine imaging protocols to optimize predictive accuracy in this vulnerable population.

Functional and structural connectivity of the subregions of the amygdala in ADHD children with or without ODD

ObjectivesThe current study aimed to investigate the structural and functional connectivity of the subregions of the amygdala in children with Attention Deficit/Hyperactivity Disorder (ADHD) only or comorbid with Oppositional Defiant Disorder (ODD).MethodsA total of 354 children with ADHD-only, 161 children with ADHD and ODD (ADHD + ODD), and 100 healthy controls were enrolled. The Child Behavior Checklist (CBCL) and the Behavior Rating Inventory of Executive Function (BRIEF) were filled out by caregivers. Analysis of covariance (ANCOVA) was performed to test group-wise differences in these behavioral measures. A subsample comprising 209 participants underwent a resting-state functional MRI scan and a diffusion-weighted imaging (DWI) scan. Functional connectivity and structural connectivity were calculated using bilateral subregions of the Amygdala as seeds. Between-group voxel-wise comparisons were conducted.ResultsThe ADHD + ODD group had more anxious/depressed moods, more delinquent and aggressive behaviors, more emotional control problems, and more inhibition deficits than the ADHD-only group (all PBonferroni−corrected < 0.05). Compared with the control and ADHD + ODD groups, the ADHD-only group displayed increased FC strength between the amygdala subregions and the left caudate, left putamen, and frontal cortex. Regarding structural connectivity (SC), the ADHD-only group demonstrated higher streamline density in the left internal capsule, corpus callosum, and the right superior corona radiata. The altered SC was associated with emotional problems in children with ADHD, while the altered FC was associated with other ADHD-related clinical features.ConclusionsAltered structural and functional connectivity of the subregions of the amygdala in children with ADHD compared with their healthy counterparts were respectively associated with ADHD-related behavioral and emotional problems.Clinical trial number: not applicable.

Genetic analysis of a child with Leukoencephalopathy with ataxia caused by a homozygous variant of CLCN2 gene and a literature review

To explore the clinical manifestations and genetic characteristics of a child with Leukoencephalopathy with ataxia (LKPAT) caused by a CLCN2 gene variant. A retrospective analysis was conducted on the clinical data of a child admitted to Hunan Children's Hospital in June 2024 due to "intermittent convulsions for 13 days". Peripheral blood samples were collected from the child and his parents for whole exome sequencing, followed by Sanger sequencing validation and pathogenicity analysis of candidate variants. Literature searches were performed using the keywords "CLCN2 gene" "chloride channel-2" "leukoencephalopathy with ataxia/LKPAT" "leukoencephalopathy" in both Chinese and English on CNKI, Wanfang, and PubMed databases. The search time was set from the establishment of the databases to July 31, 2024. Childhood-onset LKPAT literature was screened and analyzed. This study was approved by the Medical Ethics Committee of Hunan Children's Hospital (Ethics No. HCHLL-2024-351). The child was a 7-month-and-26-day-old male infant born to consanguineous parents, presenting with epileptic seizures and borderline development. Cranial MRI revealed symmetrical long T2 signal shadows in the posterior limb of the internal capsule, cerebral peduncle, pons, and middle peduncle of the cerebellum. Video electroencephalogram (EEG) showed an abnormal childhood EEG with one focal seizure. Whole exome sequencing revealed a homozygous c.2201dup (p.Glu735Ter) variant in the CLCN2 gene of the child. Sanger sequencing confirmed that the variant was inherited from both parents. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), this variant was classified as pathogenic (PVS1+PM3_Supporting+PM2_Supporting). A total of 8 relevant literature were retrieved, together with the present case, 16 childhood-onset LKPAT patients were cumulatively reported, which consisted of 9 males and 7 females. Twelve CLCN2 gene variants were involved, including 2 nonsense variants, 3 missense variants, 7 frameshifting variants, 2 c.61dup variants, and 5 c.1709G>A variants. The initial symptoms of the 16 patients included headache, ataxia, epileptic seizures, spasticity, developmental delay, lower back pain, hearing impairment, and intention tremor. Three patients had onset of the disease before the age of one, of which 2 had epileptic seizures as the initial symptom. The homozygous variant CLCN2: c.2201dup (p.Glu735Ter) is considered the pathogenic cause of LKPAT in this child, marking the first childhood-onset case reported in China. Genetic testing has facilitated the diagnosis of childhood-onset LKPAT and expanded the spectrum of CLCN2 gene mutations.

Remodeling and Characterization Analysis of Corticospinal Tract in Patients with Intracerebral Hemorrhage in the Basal Ganglia.

To investigate corticospinal tract (CST) injury and remodeling in patients with basal ganglia intracerebral hemorrhage (ICH) and explore the characterization capabilities of the corresponding parameters. In this prospective study, baseline, scale, and diffusion-weighted imaging (DWI) data were collected from patient cohorts. Participants were stratified into favorable (0-3 points) and unfavorable (4-6 points) prognosis groups, based on Modified Rankin Scale (mRS) after 3-6months. The analysis of DWI data was conducted employing FSL and DSI Studio software to compare CST injury between the prognosis groups and CST remodeling features. A partial correlation model was deployed to elucidate the characterization capability of CST-related parameters. Additionally, logistic regression analysis was applied to identify factors significantly influencing prognosis. A total of 65 patients were enrolled with a mean age of 53.52years and a median hematoma volume of 23.60ml. The 44 patients were classified within the favorable prognosis group, demonstrating a statistically significant difference in their lower mean age (P = 0.002). Additionally, 10 patients underwent DWI review with a mean age of 50.30years and a median hematoma volume of 18.56ml. The investigation uncovered evidence of CST damage versus remodeling at the group level, respectively, with statistical significance (FDR-corrected P < 0.05, 10,000 permutations). The fractional anisotropy (FA) ratio in the internal capsule region exhibited moderate correlation with motor function (r = 0.507, P < 0.001) and the 3- to 6-month mRS scores (r = - 0.318, P < 0.013). Furthermore, binary logistic regression analysis identified the FA rate in the internal capsule as a significant influencing factor of prognosis (odds ratio = 1.027, 95% confidence interval = 1.003-1.052, P = 0.025). Basal ganglia ICH can coincide with injury to the CST, which could undergo repair over time. Additionally, the FA ratio of the internal capsule is a potential biomarker to characterize residual motor function and provide prognostic information.

Involvement of the posterior limb of the internal capsule independently predicts the prognosis of patients with basal ganglia and thalamic hemorrhage.

Intracerebral hemorrhage (ICH) is the most lethal and devastating subtype of stroke. Basal ganglia hemorrhage and thalamic hemorrhage are the most common types of ICH, accounting for 50-70% of all ICH cases, leading to disability and death, and it involves the posterior limb of the internal capsule to varying degrees. In this study, we investigated the impact of varying degrees of the involvement of the posterior limb of the internal capsule on the prognosis of patients with basal ganglia and thalamic ICH and assessed whether it improves the predictive accuracy of the max-ICH score, an existing scale for ICH functional outcome. This is a multicenter, retrospective, observational study. We graded the involvement of the posterior limb of the internal capsule according to the degree of compression and injury (called iICH, ranging from 0 to 4). An unfavorable outcome was defined as a 90-day modified Rankin Scale (mRS) of > 2. Multivariate logistic regression analysis was used to identify independent risk factors associated with unfavorable prognosis. The discrimination was verified using receiver operating characteristic curve (ROC) analysis, while the calibration was verified by the Hosmer-Lemeshow test. Of the 305 patients included, 188 from Nanfang Hospital were assigned to the development cohort, and 117 from Heyuan People's Hospital and Huadu District People's Hospital were assigned to the validation cohort. In the development cohort, iICH was identified as an independent factor of a 90-day unfavorable outcome, and the area under the ROC (AUC) was 0.774. When combined with the iICH, the AUC of max-ICH was significantly elevated from 0.816 to 0.866. Comparable results were found in the validation cohort. Increased involvement of the posterior limb of the internal capsule is associated with a worse outcome in patients with basal ganglia and thalamic ICH.

Behavior Changes in Quinpirole Obsessive-Compulsive Disorder Rats Treated with 6-Hydroxydopamine and the Corresponding Dopaminergic Compulsive Loop Mechanism.

Recent studies suggest that the anterior limb of the internal capsule may be an area of convergence for multiple compulsion loops. In this study, the role of different dopaminergic compulsion loops in the mechanism of obsessive-compulsive disorder (OCD) was investigated by selectively damaging dopaminergic neurons or fibers in the corresponding targets with 6-hydroxydopamine (6-OHDA) and depicting the anatomical map of various compulsion loops located in the anterior limb of the internal capsule. A total of 52 male Sprague Dawley (SD) rats were exposed to either saline (1 mL/kg, NS group, n = 6) or quinpirole (QNP, dopamine D2-agonist, 0.5 mg/kg, n = 46) twice weekly for 5 weeks. After each injection, the rats were placed on an open field to analyze aspects of their behaviour, including the number of home base visits (NOH), average time between each home base visit (ATBO), and total distance travelled (TDM). After model setup, 46 QNP rats were divided randomly into five groups: 6-OHDA anterior limb of internal capsule (AC) stereotactic injection group (QNP+AC group, n = 10), 6-OHDA mediodorsal thalamic nucleus (MD) stereotactic injection group (QNP+MD group, n = 10), 6-OHDA nucleus accumbens (NAC) stereotactic injection group (QNP+NAC group, n = 10), saline stereotactic injection group (QNP+NS-S group, n = 10), and non-surgical group (QNP+Non-S group, n = 6). In the NS group, rats simultaneously received a 6-OHDA stereotactic injection (NS+6-OHDA-S group, n = 6: AC2, MD2, NAC2). All QNP-treated rats were then continued to be given QNP twice a week for 4 weeks, and their behaviour was observed after each infusion. After 4 weeks, immunofluorescence staining was used to monitor the distribution of dopamine neurons and nerve fibers in different areas of the intervention nerve loops, and quantitative analysis was performed. Compulsive behaviour declined gradually in the QNP+AC and QNP+NAC groups 3 and 4 weeks after surgery, with the QNP+AC group decreasing more rapidly. The QNP+MD group had decreased by 3 weeks after surgery but increased to almost the same level as pre-surgery at 4 weeks post-surgery. Postoperative fluorescence staining and quantitative analysis suggested the number of dopamine (DA) neurons or nerve fibers in the corresponding target area of the 6-OHDA injection were significantly reduced compared with the QNP+Non-S group. 6-OHDA selectively damages the targets of dopaminergic neurons or nerve fibers within the OCD loop, which somewhat alleviates compulsive behaviours. The results suggest that the AC might be the best target for therapeutic interventions for OCD.

Evaluation of gray-matter and white-matter microstructural abnormalities in children with growth hormone deficiency: a comprehensive assessment with synthetic magnetic resonance imaging.

Pediatric growth hormone deficiency (GHD) is a disease resulting from the impaired growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis, but the effects of GHD on children's behavior and brain microstructural structure alterations have not yet been fully clarified. We aimed to investigate the quantitative profiles of gray matter and white matter in pediatric GHD using synthetic magnetic resonance imaging (MRI). The data of 50 children with GHD and 50 typically developing (TD) children were prospectively collected. Group differences in brain volumetric parameters, individual-level T1 and T2 relaxometry values, and myelin volume fraction (MVF) were assessed. Subsequently, magnetic resonance-based indices with significant differences between groups were correlated with clinical variables via partial correlation. Compared with TD children, children with GHD showed significantly decreased whole-brain gray-matter volume [P false discovery rate (PFDR) <0.001] and increased non-gray-matter/white-matter/cerebrospinal fluid (NoN) volume (PFDR<0.001). For gray-matter microstructural profiles, altered T1 and T2 relaxometry values in children with GHD were mainly distributed in the default mode (PFDR<0.001) and central executive networks (PFDR<0.001). For white-matter microstructural profiles, widespread increased regional MVF was mainly distributed in the corpus callosum, corticospinal tract, internal capsule, external capsule, and cingulum (all PFDR values <0.001). Meanwhile, the T2 relaxation values in the left cuneus (r=0.400; P=0.005) and MVF in the right corticospinal tract (r=0.313; P=0.032) had a positive relationship with IGF-1. Altered T1 and T2 relaxometry values and MVF in gray and white matter indicate the relevance of the default mode, central executive, somatosensory, visual, and cerebellar networks underlying pediatric GHD, which may imply the involvement of the GH-IGF-1 axis and myelin in the pathophysiological mechanism of GHD. Moreover, the brain microstructure alteration in cortico-striatal-limbic loop might be influenced by the GH-IGF-1 axis and play an important role in the behavioral impairments in children with GHD.

The impact of cortical and subcortical volumes on major depression risk: A genetic study.

This study aimed to explore the causal relationship between brain cortical and subcortical structures and major depressive disorder (MDD) using the Mendelian Randomization (MR) method. Single nucleotide polymorphisms (SNPs) were used as instrumental variables to analyze subcortical brain volume, cortical thickness, and surface area as exposure factors, with MDD as the outcome. Multiple sensitivity analyses were conducted to validate the robustness of the results. MR analysis showed a significant negative correlation between subcortical brain volume and MDD. Specifically, the volumes of the caudate nucleus, hippocampus, intracranial region, and thalamus were inversely associated with the risk of MDD, indicating that larger subcortical brain volumes were linked to a lower risk of MDD. The thickness of the entorhinal cortex was also negatively correlated with MDD. At the same time, certain cortical regions showed significant positive correlations between surface area and MDD. Increased thickness of the entorhinal cortex and increased surface areas of the isthmus of the cingulate gyrus, middle temporal gyrus, and precuneus were associated with a higher risk of MDD. The sensitivity analyses revealed no significant heterogeneity or horizontal pleiotropy, and the results were consistent across different methods, confirming their robustness. The study found that increased volumes of the caudate nucleus, hippocampus, internal capsule, and thalamus in subcortical brain regions and increased thickness of the entorhinal cortex in cortical regions were associated with a reduced risk of MDD, while increased surface areas of the isthmus of the cingulate gyrus, middle temporal gyrus, and precuneus in cortical regions were linked to an elevated risk of MDD.

Myelin measurement in amyotrophic lateral sclerosis with synthetic MRI: A potential diagnostic and predictive method

Background: Myelin damage has recently been highlighted as a major causative factor of amyotrophic lateral sclerosis (ALS). Although myelin damage has been pathologically identified in ALS, it has not been clinically evaluated. This study aimed to quantify myelin volume using synthetic MRI to evaluate myelin damage in patients with ALS, and determine its association with clinical parameters.Methods: We evaluated patients with ALS (n = 35) and individuals (n = 16) without intracranial disease using synthetic magnetic resonance imaging (MRI) and measured total myelin volume (TMV), myelin fraction (MYF), and myelin partial volume (VMY) in the cerebral peduncle and the posterior limb of the internal capsule (PLIC). We also investigated factors associated with acquired quantitative values.Results: The TMV was significantly lower in the patients with ALS than in the control group (P = 0.045). The TMV (r = 0.42, P = 0.013) and MYF (r = 0.34, P = 0.047) significantly correlated with Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores in the patients, and MYF was independent of the traditional white matter lesion grading score. The VMY of the PLIC was significantly lower in the ALS than the control group (P = 0.018), and the ALS group significantly correlated with ALSFRS-R scores (r = 0.36, P = 0.033).Conclusions: Myelin damage can be quantified by synthetic MRI as reduced myelin volume, with the possibility of predicting prognoses in patients with ALS. Furthermore, myelin measurements in the PLIC might be a novel diagnostic marker for ALS.

Multidimensional structural analyses revealed a correlation between thalamic atrophy and white matter degeneration in idiopathic dystonia.

Although aberrant changes in grey and white matter are core features of idiopathic dystonia, few studies have explored the correlation between grey and white matter changes in this disease. This study aimed to investigate the coupling correlation between morphological and microstructural alterations in patients with idiopathic dystonia. Structural T1 imaging and diffusion tensor imaging were performed on a relatively large cohort of patients. Multidimensional structural analyses, including voxel-based analyses, voxel-based morphology, fixel-based analyses and surface-based morphometry, were performed to explore these structural alterations. Probabilistic tractography and correlation analyses were employed to examine these relationships. A total of 147 patients with idiopathic dystonia and 137 healthy controls were recruited in this study. There were no significant differences in the cortical morphometry between patients with idiopathic dystonia and healthy controls using voxel- and surface-based morphometry. However, the grey matter volume of the bilateral thalamus, fractional anisotropy in the right anterior corona radiata, right retrolenticular part of the internal capsule and right posterior corona radiata, and the fibre density and cross-section combined in the fibre tract connecting the left ventral posterolateral thalamic nucleus and left area 5 m, were significantly decreased in patients with idiopathic dystonia compared with those in healthy controls. Furthermore, the reduced grey matter volume in the right thalamus not only correlated with the disease duration but also with the reduced fractional anisotropy in the right posterior corona radiata and decreased the fibre density and cross-section combined in the fibre tract connecting the left ventral posterolateral thalamic nucleus and the left area 5 m in patients with idiopathic dystonia. These findings suggest that the thalamus is structurally impaired in idiopathic dystonia and that microstructural disruption in thalamocortical projections occurs secondary to thalamic atrophy.

Distinct impact modes of polygenic disposition to dyslexia in the adult brain.

Dyslexia is a common and partially heritable condition that affects reading ability. In a study of up to 35,231 adults, we explored the structural brain correlates of genetic disposition to dyslexia. Individual dyslexia-disposing genetic variants showed distinct patterns of association with brain structure. Independent component analysis revealed various brain networks that each had their own genomic profiles related to dyslexia susceptibility. Circuits involved in motor coordination, vision, and language were implicated. Polygenic scores for eight traits genetically correlated with dyslexia, including cognitive, behavioral, and reading-related psychometric measures, showed partial similarities to dyslexia in terms of brain-wide associations. Notably, microstructure of the internal capsule was consistently implicated across all of these genetic dispositions, while lower volume of the motor cortex was more specifically associated with dyslexia genetic disposition alone. These findings reveal genetic and neurobiological features that may contribute to dyslexia and its associations with other traits at the population level.

Therapeutic DBS for OCD Suppresses the Default Mode Network.

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 (3responders, 2 non-responders), we conducted a DBS On/Off cycling paradigm during the acquisition of functional MRI (23fMRI 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 ismediated by interruption of communication through structural white matter connections surrounding the DBS active contacts.

Diabetes may contribute to cognitive impairment in Parkinson's disease via damaging white matter tracts.

Parkinson's disease with dementia (PDD) severely affects the quality of life of patients with Parkinson's disease (PD) in the later stages. Recently, PD patients with diabetes were found to have a higher risk of cognitive decline and developing dementia with a faster progression, but the underlying mechanism remains unclear. Diabetes-related white matter damage may partially explain the mechanism by which diabetes participates in PDD. Seventy PD patients were included. PD patients underwent diffusion tensor imaging from The Second Affiliated Hospital of Chongqing Medical University were collected and were divided into four groups: PD with diabetes without dementia, PD with dementia without diabetes, PD without dementia and diabetes. Tract-based spatial statistics analysis and region-of-interest-based analysis were performed. Factorial analysis with diabetes and dementia taken as the main effects was performed, and the differences between the white matter fibers of PD patients from the four groups were also analyzed. The interaction between diabetes and dementia in the damage of white matter in PD patients was also analyzed. We found that both diabetes and dementia were found to be related to the damage in internal capsule, corona radiata, and thalamic radiation of the PD patients. There is an interaction between diabetes and dementia in the white matter damage of PD patients. Both diabetes and dementia were found to be related to the damage in internal capsule, corona radiata, and thalamic radiation of the PD patients. Diabetes may participate in cognitive decline in PD patients via damaging cognition-related white matter tracts.

Assessment of myelination development in neonatal rats using chemical exchange saturation transfer (CEST) 7-T MRI.

Myelination is a crucial process in the nervous system. This study aimed to evaluate the progression of myelin sheath development in different brain regions of neonatal rats at distinct developmental stages using Chemical Exchange Saturation Transfer (CEST) 7-T MRI. Male SD rats of different ages (3days, 1week, 2weeks, 3weeks, 1month, 2months) were selected for the study. Advanced in vivo MRI experiments were conducted using a 7-T MRI scanner. Custom MatLab scripts were employed to generate MR images and process the data. Myelin staining was used to assess myelin distribution in various brain regions. Statistical analysis was performed using repeated measures multivariate analysis of variance (MANOVA) and Spearman's rank correlation. The progression of myelination was significantly different in different brain regions (F(5, 30) = 3.34, P < 0.05), with the corpus callosum showing an accelerated rate of myelination. Within the first month alone, there was an increase of 46.1% in myelination (t(35) = 2.29, P < 0.05). The hypothalamus and internal capsule exhibited a more gradual yet consistent increase in myelination over the two-month period, with increases of 47.1% (t(35) = 2.27, P < 0.05) and 39.8% (t(35) = 2.59, P < 0.05), respectively. A substantial positive correlation was found between the MRI-based and histological measurements of myelination (r = 0.31, P < 0.05). This study demonstrates the potential of CEST 7-T MRI as a non-invasive tool for assessing myelination progression and provides insights into the differential myelination rates across various brain regions during early development.

7-Tesla magnetic resonance imaging for monitoring microstructural changes in the lenticulostriate artery-neural complex in patients with hypertension.

The lenticulostriate artery-neural complex (LNC), which includes the lenticulostriate artery (LSA) and surrounding neural structure, is a new concept proposed by neurologists and plays a pivotal role in hypertension-induced stroke. Conventional low-magnitude magnetic resonance imaging (MRI) has not been successfully used to reveal the microstructural changes of the LNC. This study aimed to evaluate the microstructural changes of the LNC in patients with prestroke hypertension using 7-Tesla (7-T) MRI and to identify the potential MRI biomarkers for monitoring hypertension-related neurological disorders. This prospective, cross-sectional study was conducted in Chongqing, China, from February 2023 to January 2024. Its protocol complied with the Declaration of Helsinki (revised in 2013) and was approved by the Medical Science Research Ethics Committee of Southwest Hospital, Third Military Medical University, and all participants provided written informed consent. Patients with hypertension (N=32) and age-matched healthy volunteers (N=30) were enrolled. All participants underwent 7-T MRI. The number, length, and tortuosity of the LSA were measured, as were the volumes of the basal ganglia, internal capsule, and thalamus. The relationship between the LSA features and the neural structure volumes was also analyzed through partial correlation analysis. The stem, lengths of the LSA, and volume of nerve structure in LNC showed significant differences between the two groups (P<0.05). In the right hemisphere, the stem number of LSA was higher than that in the healthy group (P<0.05). Furthermore, the volumes of the globus pallidus, putamen, thalamus, caudate nucleus, and internal capsule were found to be significantly larger in healthy participants than in patients with hypertension (P<0.05). The tortuosity of the LSA was positively correlated with the internal capsule volume in the left hemisphere (r=0.460; P<0.001) and the globus pallidus (r=0.517; P<0.001). For the right hemisphere, there was a positive correlation between the stems number in the LSA and the volume of the internal capsules (r=0.340; P=0.007) and the globus pallidus (r=0.299; P=0.018). The tortuosity of the LSA was positively correlated with the volume of the internal capsule (r=0.504; P<0.001) and globus pallidus (r=0.431; P<0.001). Meanwhile, we found the number of LSA branches entering the putamen was higher in healthy individuals than in patients with hypertension (P<0.01). Using 7-T MRI, we obtained ultrahigh-resolution images of the LNC and found that the microstructures of LNC were changed in the prestroke patients with hypertension. MRI monitoring of microstructural changes in LNC, including the number of LSA stems and the internal capsule and globus pallidus volume, may serve as predictive biomarkers for intracranial changes and potential complications caused by hypertension.

MCI Diagnosis and Neighborhood Disadvantage Predict Differences in White Matter Microstructure in a Rural Aging Cohort

AbstractBackgroundDiffusion magnetic resonance imaging (dMRI) studies show cerebral white matter alterations are associated with both mild cognitive impairment (MCI) and contextual psychosocial factors. However, these reports are almost exclusively based on older adults residing in metropolitan areas. Individuals living in rural communities face increased risk for Alzheimer’s disease and related dementias, but little is known regarding the sensitivity of dMRI markers to incident MCI or psychosocial stressors in this population. In a rural‐dwelling community cohort of older adults, this study evaluated associations between dMRI measures of white matter microstructure and both clinical MCI diagnosis and neighborhood disadvantage.MethodThe study sample included rural‐dwelling older adults (n=69) from the Nevada Exploratory Alzheimer’s Disease Research Center. Participants were characterized as cognitively unimpaired (CU; n=42) or diagnosed with MCI (n=27) based on clinical expert consensus, and all had dMRI data and Area Deprivation Index (ADI) measures of neighborhood disadvantage. dMRI data processing leveraged the MRtrix3 fixel‐based analysis framework and free water mapping to estimate voxel‐based measures of white matter organization, transformed to a sample template. Data analysis utilized voxel‐based analysis (VBA) to model differences in clinical diagnosis and ADI scores as predictors of fiber density, crossing fiber entropy, and extracellular free water, and free water‐corrected diffusion tensor parameters, accounting for differences in age, sex, and handedness.ResultsThe VBA models showed both MCI diagnosis and elevated neighborhood disadvantage predicted significantly greater (familywise error corrected p&lt;.05) free water and reduced crossing fiber entropy in centrum semiovale and internal capsule (Figure 1). Uncorrected models for both diagnosis and higher ADI level revealed widespread associations with dMRI measures of free water, tensor parameters, and fiber density that were nonsignificant following permutation‐based corrections.ConclusionThese preliminary findings reveal white matter alterations associated with consensus MCI diagnosis and to socioeconomic differences in a clinical cohort of rural‐dwelling older adults. The present results highlight the value of modeling extracellular cerebral spinal fluid or ‘free water’ as a marker of microstructural changes associated with both cognitive impairment and contextual psychosocial factors. Future efforts are needed to compare these effects between rural‐ and metropolitan‐dwelling older adults at risk for dementia.

White matter functional and structural alterations of spinocerebellar ataxia type 3: A longitudinal MRI study.

Widespread white matter (WM) microstructural abnormalities have been reported in patients with spinocerebellar ataxia type 3 (SCA3) using diffusion tensor imaging (DTI), whereas the ability of DTI to detect WM degeneration over short-term period remains insufficiently explored. Additionally, WM dysfunction remains entirely unknown in this disease. This study aims to investigate WM structural and functional alterations in SCA3, and provide promising progression biomarkers for short-term clinical trials. DTI and resting-state functional magnetic resonance imaging data of 52 SCA3 patients and 56 healthy controls (HCs) were collected at baseline. After a mean follow-up of 1year, MRI scans were performed on a subset of 28 SCA3 patients. Compared with HCs, widespread WM structural and functional abnormalities were observed in patients with SCA3. Between-group differences of both structural and functional MR metrics showed remarkable similarities, with large differences located in pons and corticospinal tracts, involving cerebellar WM, cerebellar and cerebral peduncles, medial lemniscus and bilateral posterior limb of internal capsule (PLIC). The longitudinal analysis further showed decreased ALFF in the right PLIC and increased mean diffusivity in the left inferior cerebellar peduncle and right medial lemniscus over time in SCA3 patients. These findings emphasized that pons and the CST were the most vulnerable WM areas in SCA3, and have the potential to become therapeutic targets of SCA3 for upcoming interventional trials. In addition, both DT metrics and WM ALFF were efficient progression biomarkers for SCA3 even in short-term period.