High baseline perivascular space volume in basal ganglia is associated with attention and executive function decline in Parkinson's disease.

BACKGROUND: Pathologic perivascular spaces (PVS), the fluid-filled compartments surrounding brain vasculature, may underlie cognitive decline in Parkinson's disease (PD). However, whether this impacts specific cognitive domains has not been investigated. OBJECTIVES: This study examined the relationship of PVS volume at baseline with domain-specific and global cognitive change over 2 years in PD individuals. METHODS: A total of 39 individuals with PD underwent 3T T1w magnetic resonance imaging to determine PVS volume fraction (PVS volume normalized to total regional volume) within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, and superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of cognitive domains and global cognitive function at baseline and after 2 years. RESULTS: Higher basal ganglia PVS at baseline was associated with greater decline in attention, executive function, and global cognition scores. CONCLUSIONS: While previous reports have associated elevated PVS volume in the basal ganglia with decline in global cognition in PD, our findings show such decline may affect the attention and executive function domains.

Ophthalmic Artery Morphology and Hemodynamics Associated with White Matter Hyperintensity.

Purpose: To investigate morphological and hemodynamic characteristics of the ophthalmic artery (OA) in patients with white matter hyperintensity (WMH), and the association of the presence and severity of WMH with OA characteristics. Methods: This cross-sectional study included 44 eyes of 25 patients with WMH and 38 eyes of 19 controls. The Fazekas scale was adopted as criteria for evaluating the severity of white matter hyperintensities. The morphological characteristics of the OA were measured on the basis of three-dimensional reconstruction. The hemodynamic parameters of the OA were calculated using computational fluid dynamics simulations. Results: Compared with the control group, the diameter (16.0±0.27 mm vs. 1.71±0.18 mm, P=0.029), median blood flow velocity (0.12 m/s vs. 0.22 m/s, P<0.001), mass flow ratio (2.16% vs. 3.94%, P=0.012) and wall shear stress (2.65 Pa vs. 9.31 Pa, P<0.001) of the OA in patients with WMH were significantly decreased. After adjusting for confounding factors, the diameter, blood flow velocity, wall shear stress, and mass flow ratio of the OA were significantly associated with the presence of WMH. Male sex and high low-density protein level were associated with moderate-to-severe total WMH, and smoking was associated with the moderate-to-severe periventricular WMH. Conclusions: The diameter, blood flow velocity, mass flow ratio, and wall shear stress of the OA were independently associated with the presence of WMH. Atherosclerosis might be involved in the common mechanism of the occurrence of WMH and the OA changes.

Physical reserve and its underpinning functional neural networks moderate the relationship between white matter hyperintensity and postural balance in older adults with subcortical ischemic vascular cognitive impairment.

White matter hyperintensities (WMH) are markers of subcortical ischemic vascular cognitive impairment (SIVCI) associated with impaired postural balance. Physical reserve (PR) is a recently established construct that reflects one's capacity to maintain physical function despite brain pathology. This cross-sectional study aims to map functional networks associated with PR, and examining the relationship between PR, WMH, and postural balance. PR was defined in 22 community-dwelling older adults with SIVCI. Functional networks of PR were computed using general linear model. Subsequent analyses examined whether PR and relevant networks moderated the relationship between WMH and postural balance under two conditions-eyes open while standing on foam (EOF) or on floor (EONF). We found that PR and the relevant networks-frontoparietal network (FPN) and default mode network (DMN)-significantly moderated the association between WMH and postural balance. For individuals with high PR, postural balance remained stable regardless of the extent of WMH load; whereas for those with low PR, postural balance worsened as WMH load increased. These results suggest the attenuated effects of WMH on postural stability due to PR may be underpinned by functional neural network reorganization in the FPN and DMN as a part of compensatory processes.

Prolonged ventricular repolarization associated with mild cognitive impairment and white matter hyperintensities: a cross-sectional study.

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen's criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.

A proof of concept model to calculate white and grey matter AIS injuries in pedestrian collisions.

In the real world, the severity of traumatic injuries is measured using the Abbreviated Injury Scale (AIS) and is often estimated, in finite element human computer models, with the maximum principal strains (MPS) tensor. MPS can predict when a serious injury is reached, but cannot provide any AIS measures lower and higher from this. To overcome these limitations, a new organ trauma model (OTM2), capable of calculating the threat to life of any organ injured, is proposed. The OTM2 model uses a power method, namely peak virtual power, and defines brain white and grey matters trauma responses. It includes human age effect (volume and stiffness), localised impact contact stiffness and provides injury severity adjustments for haemorrhaging. The focus, in this case, is on real-world pedestrian brain injuries. OTM2 model was tested against three real-life pedestrian accidents and has proven to reasonably predict the post mortem (PM) outcome. Its AIS predictions are closer to the real-world injury severity than the standard maximum principal strain (MPS) methods currently used. This proof of concept suggests that OTM2 has the potential to improve forensic predictions as well as contribute to the improvement in vehicle safety design through the ability to measure injury severity. This study concludes that future advances in trauma computing would require the development of a brain model that could predict haemorrhaging.

Distinct grey and white matter changes are associated with the phenomenology of visual hallucinations in Lewy Body Disease.

Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a variety of phenomena, such as illusions, presence and passage hallucinations occurring at early stages of LBD. The neural mechanisms of visual hallucinations are largely unknown. The hodotopic model posits that the hallucination state is due to abnormal activity in specialized visual areas, that occurs in the context of wider network connectivity alterations and that phenomenology of VH, including content and temporal characteristics, may help identify brain regions underpinning these phenomena. Here we investigated both the topological and hodological neural basis of visual hallucinations integrating grey and white matter imaging analyses. We studied LBD patients with VH and age matched healthy controls (HC). VH were assessed using a North-East-Visual-Hallucinations-Interview that captures phenomenological detail. Then we applied voxel-based morphometry and tract based spatial statistics approaches to identify grey and white matter changes. First, we compared LBD patients and HC. We found a reduced grey matter volume and a widespread damage of white tracts in LBD compared to HC. Then we tested the association between CVH and MVH and grey and white matter indices. We found that CVH duration was associated with decreased grey matter volume in the fusiform gyrus suggesting that LBD neurodegeneration-related abnormal activity in this area is responsible for CVH. An unexpected finding was that MVH severity was associated with a greater integrity of white matter tracts, specifically those connecting dorsal, ventral attention networks and visual areas. Our results suggest that networks underlying MVH need to be partly intact and functional for MVH experiences to occur, while CVH occur when cortical areas are damaged. The findings support the hodotopic view and the hypothesis that MVH and CVH relate to different neural mechanisms, with wider implications for the treatment of these symptoms in a clinical context.

End-stage renal disease accompanied by mild cognitive impairment: A study and analysis of trimodal brain network fusion.

The function and structure of brain networks (BN) may undergo changes in patients with end-stage renal disease (ESRD), particularly in those accompanied by mild cognitive impairment (ESRDaMCI). Many existing methods for fusing BN focus on extracting interaction features between pairs of network nodes from each mode and combining them. This approach overlooks the correlation between different modal features during feature extraction and the potentially valuable information that may exist between more than two brain regions. To address this issue, we propose a model using a multi-head self-attention mechanism to fuse brain functional networks, white matter structural networks, and gray matter structural networks, which results in the construction of brain fusion networks (FBN). Initially, three networks are constructed: the brain function network, the white matter structure network, and the individual-based gray matter structure network. The multi-head self-attention mechanism is then applied to fuse the three types of networks, generating attention weights that are transformed into an optimized model. The optimized model introduces hypergraph popular regular term and L1 norm regular term, leading to the formation of FBN. Finally, FBN is employed in the diagnosis and prediction of ESRDaMCI to evaluate its classification performance and investigate the correlation between discriminative brain regions and cognitive dysfunction. Experimental results demonstrate that the optimal classification accuracy achieved is 92.80%, which is at least 3.63% higher than the accuracy attained using other methods. This outcome confirms the effectiveness of our proposed method. Additionally, the identification of brain regions significantly associated with scores on the Montreal cognitive assessment scale may shed light on the underlying pathogenesis of ESRDaMCI.

Deep brain stimulation of symptom-specific networks in Parkinson's disease.

Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease. Potentially, improving each symptom may require stimulation of different white matter tracts. Here, we study a large cohort of patients (N = 237 from five centers) to identify tracts associated with improvements in each of the four symptom domains. Tremor improvements were associated with stimulation of tracts connected to primary motor cortex and cerebellum. In contrast, axial symptoms are associated with stimulation of tracts connected to the supplementary motor cortex and brainstem. Bradykinesia and rigidity improvements are associated with the stimulation of tracts connected to the supplementary motor and premotor cortices, respectively. We introduce an algorithm that uses these symptom-response tracts to suggest optimal stimulation parameters for DBS based on individual patient's symptom profiles. Application of the algorithm illustrates that our symptom-tract library may bear potential in personalizing stimulation treatment based on the symptoms that are most burdensome in an individual patient.

C1-2 hypermobility and its impact on the spinal cord: a finite element analysis.

OBJECTIVE: The authors present a finite element analysis (FEA) evaluating the mechanical impact of C1-2 hypermobility on the spinal cord. METHODS: The Code_Aster program was used to perform an FEA to determine the mechanical impact of C1-2 hypermobility on the spinal cord. Normative values of Young's modulus were applied to the various components of the model, including bone, ligaments, and gray and white matter. Two models were created: 25° and 50° of C1-on-C2 rotation, and 2.5 and 5 mm of C1-on-C2 lateral translation. Maximum von Mises stress (VMS) throughout the cervicomedullary junction was calculated and analyzed. RESULTS: The FEA model of 2.5 mm lateral translation of C1 on C2 revealed maximum VMS for gray and white matter of 0.041 and 0.097 MPa, respectively. In the 5-mm translation model, the maximum VMS for gray and white matter was 0.069 and 0.162 MPa. The FEA model of 25° of C1-on-C2 rotation revealed maximum VMS for gray and white matter of 0.052 and 0.123 MPa. In the 50° rotation model, the maximum VMS for gray and white matter was 0.113 and 0.264 MPa. CONCLUSIONS: This FEA revealed significant spinal cord stress during pathological rotation (50°) and lateral translation (5 mm) consistent with values found during severe spinal cord compression and in patients with myelopathy. While this finite element model requires oversimplification of the atlantoaxial joint, the study provides biomechanical evidence that hypermobility within the C1-2 joint leads to pathological spinal cord stress.

The role of language-related functional brain regions and white matter tracts in network plasticity of post-stroke aphasia.

The neural mechanisms underlying language recovery after a stroke remain controversial. This review aimed to summarize the plasticity and reorganization mechanisms of the language network through neuroimaging studies. Initially, we discussed the involvement of right language homologues, perilesional tissue, and domain-general networks. Subsequently, we summarized the white matter functional mapping and remodeling mechanisms associated with language subskills. Finally, we explored how non-invasive brain stimulation (NIBS) promoted language recovery by inducing neural network plasticity. It was observed that the recruitment of right hemisphere language area homologues played a pivotal role in the early stages of frontal post-stroke aphasia (PSA), particularly in patients with larger lesions. Perilesional plasticity correlated with improved speech performance and prognosis. The domain-general networks could respond to increased "effort" in a task-dependent manner from the top-down when the downstream language network was impaired. Fluency, repetition, comprehension, naming, and reading skills exhibited overlapping and unique dual-pathway functional mapping models. In the acute phase, the structural remodeling of white matter tracts became challenging, with recovery predominantly dependent on cortical activation. Similar to the pattern of cortical activation, during the subacute and chronic phases, improvements in language functions depended, respectively, on the remodeling of right white matter tracts and the restoration of left-lateralized language structural network patterns. Moreover, the midline superior frontal gyrus/dorsal anterior cingulate cortex emerged as a promising target for NIBS. These findings offered theoretical insights for the early personalized treatment of aphasia after stroke.

Structural Neuroplasticity Effects of Singing in Chronic Aphasia.

Singing-based treatments of aphasia can improve language outcomes, but the neural benefits of group-based singing in aphasia are unknown. Here, we set out to determine the structural neuroplasticity changes underpinning group-based singing-induced treatment effects in chronic aphasia. Twenty-eight patients with at least mild nonfluent poststroke aphasia were randomized into two groups that received a 4-month multicomponent singing intervention (singing group) or standard care (control group). High-resolution T1 images and multishell diffusion-weighted MRI data were collected in two time points (baseline/5 months). Structural gray matter (GM) and white matter (WM) neuroplasticity changes were assessed using language network region of interest-based voxel-based morphometry (VBM) and quantitative anisotropy-based connectometry, and their associations to improved language outcomes (Western Aphasia Battery Naming and Repetition) were evaluated. Connectometry analyses showed that the singing group enhanced structural WM connectivity in the left arcuate fasciculus (AF) and corpus callosum as well as in the frontal aslant tract (FAT), superior longitudinal fasciculus, and corticostriatal tract bilaterally compared with the control group. Moreover, in VBM, the singing group showed GM volume increase in the left inferior frontal cortex (Brodmann area 44) compared with the control group. The neuroplasticity effects in the left BA44, AF, and FAT correlated with improved naming abilities after the intervention. These findings suggest that in the poststroke aphasia group, singing can bring about structural neuroplasticity changes in left frontal language areas and in bilateral language pathways, which underpin treatment-induced improvement in speech production.

Alterations of the cerebral microstructure in patients with noise-induced hearing loss: A diffusion tensor imaging study.

OBJECTIVE: To explore the changes in the cerebral microstructure of patients with noise-induced hearing loss (NIHL) using diffusion tensor imaging (DTI). METHOD: Overall, 122 patients with NIHL (mild [MP, n = 79], relatively severe patients [including moderate and severe; RSP, n = 32], and undetermined [lost to follow-up, n = 11]) and 84 healthy controls (HCs) were enrolled. All clinical data, including age, education level, hearing threshold, occupation type, noise exposure time, and some scale scores (including the Mini-Mental State Examination [MMSE], tinnitus handicap inventory [THI], and Hamilton Anxiety Scale [HAMA]), were collected and analyzed. All participants underwent T1WI3DFSPGR and DTI, and tract-based spatial statistics and region of interest (ROI) analysis were used for assessment. RESULTS: The final sample included 71 MP, 28 RSP, and 75 HCs. The HAMA scores of the three groups were significantly different (p < .05). The noise exposure times, hearing thresholds, and HAMA scores of the MP and RSP were significantly different (p < .05). The noise exposure time was positively correlated with the hearing threshold and negatively correlated with the HAMA scores (p < .05), whereas the THI scores were positively correlated with the hearing threshold (p < .05). DTI analysis showed that all DTI parameters (fractional anisotropy [FA], axial diffusivity [AD], mean diffusivity [MD], and radial diffusivity [RD]) were significantly different in the left inferior longitudinal fasciculus (ILF) and left inferior fronto-occipital fasciculus (IFOF) for the three groups (p < .05). In addition, the FA values were significantly lower in the bilateral corticospinal tract (CST), right fronto-pontine tract (FPT), right forceps major, left superior longitudinal fasciculus (temporal part) (SLF), and left cingulum (hippocampus) (C-H) of the MP and RSP than in those of the HCs (p < .05); the AD values showed diverse changes in the bilateral CST, left IFOF, right anterior thalamic radiation, right external capsule (EC), right SLF, and right superior cerebellar peduncle (SCP) of the MP and RSP relative to those of the HC (p < .05). However, there were no significant differences among the bilateral auditory cortex ROIs of the three groups (p > .05). There was a significant negative correlation between the FA and HAMA scores for the left IFOF/ILF, right FPT, left SLF, and left C-H for the three groups (p < .05). There was a significant positive correlation between the AD and HAMA scores for the left IFOF/ILF and right EC of the three groups (p < .05). There were significantly positive correlations between the RD/MD and HAMA scores in the left IFOF/ILF of the three groups (p < .05). There was a significant negative correlation between the AD in the right SCP and noise exposure time of the MP and RSP groups (p < .05). The AD, MD, and RD in the left ROI were significantly positively correlated with hearing threshold in the MP and RSP groups (p < .05), whereas FA in the right ROI was significantly positively correlated with the HAMA scores for the three groups (p < .05). CONCLUSION: The changes in the white matter (WM) microstructure may be related to hearing loss caused by noise exposure, and the WM structural abnormalities in patients with NIHL were mainly located in the syndesmotic fibers of the temporooccipital region, which affected the auditory and language pathways. This confirmed that the auditory pathways have abnormal structural connectivity in patients with NIHL.

Callosal Interhemispheric Communication in Mild Traumatic Brain Injury: A Mediation Analysis on WM Microstructure Effects.

BACKGROUND AND PURPOSE: Because the corpus callosum connects the left and right hemispheres and a variety of WM bundles across the brain in complex ways, damage to the neighboring WM microstructure may specifically disrupt interhemispheric communication through the corpus callosum following mild traumatic brain injury. Here we use a mediation framework to investigate how callosal interhemispheric communication is affected by WM microstructure in mild traumatic brain injury. MATERIALS AND METHODS: Multishell diffusion MR imaging was performed on 23 patients with mild traumatic brain injury within 1 month of injury and 17 healthy controls, deriving 11 diffusion metrics, including DTI, diffusional kurtosis imaging, and compartment-specific standard model parameters. Interhemispheric processing speed was assessed using the interhemispheric speed of processing task (IHSPT) by measuring the latency between word presentation to the 2 hemivisual fields and oral word articulation. Mediation analysis was performed to assess the indirect effect of neighboring WM microstructures on the relationship between the corpus callosum and IHSPT performance. In addition, we conducted a univariate correlation analysis to investigate the direct association between callosal microstructures and IHSPT performance as well as a multivariate regression analysis to jointly evaluate both callosal and neighboring WM microstructures in association with IHSPT scores for each group. RESULTS: Several significant mediators in the relationships between callosal microstructure and IHSPT performance were found in healthy controls. However, patients with mild traumatic brain injury appeared to lose such normal associations when microstructural changes occurred compared with healthy controls. CONCLUSIONS: This study investigates the effects of neighboring WM microstructure on callosal interhemispheric communication in healthy controls and patients with mild traumatic brain injury, highlighting that neighboring noncallosal WM microstructures are involved in callosal interhemispheric communication and information transfer. Further longitudinal studies may provide insight into the temporal dynamics of interhemispheric recovery following mild traumatic brain injury.

Associations of conservatism and jumping to conclusions biases with aberrant salience and default mode network.

AIM: While conservatism bias refers to the human need for more evidence for decision-making than rational thinking expects, the jumping to conclusions (JTC) bias refers to the need for less evidence among individuals with schizophrenia/delusion compared to healthy people. Although the hippocampus-midbrain-striatal aberrant salience system and the salience, default mode (DMN), and frontoparietal networks ("triple networks") are implicated in delusion/schizophrenia pathophysiology, the associations between conservatism/JTC and these systems/networks are unclear. METHODS: Thirty-seven patients with schizophrenia and 33 healthy controls performed the beads task, with large and small numbers of bead draws to decision (DTD) indicating conservatism and JTC, respectively. We performed independent component analysis (ICA) of resting functional magnetic resonance imaging (fMRI) data. For systems/networks above, we investigated interactions between diagnosis and DTD, and main effects of DTD. We similarly applied ICA to structural and diffusion MRI to explore the associations between DTD and gray/white matter. RESULTS: We identified a significant main effect of DTD with functional connectivity between the striatum and DMN, which was negatively correlated with delusion severity in patients, indicating that the greater the anti-correlation between these networks, the stronger the JTC and delusion. We further observed the main effects of DTD on a gray matter network resembling the DMN, and a white matter network connecting the functional and gray matter networks (all P < 0.05, family-wise error [FWE] correction). Function and gray/white matter showed no significant interactions. CONCLUSION: Our results support the novel association of conservatism and JTC biases with aberrant salience and default brain mode.

Disrupted topological properties of structural brain networks present a glutamatergic neuropathophysiology in people with narcolepsy.

STUDY OBJECTIVES: Growing evidences have documented various abnormalities of the white matter bundles in people with narcolepsy. We sought to evaluate topological properties of brain structural networks, and their association with symptoms and neuropathophysiological features in people with narcolepsy. METHODS: Diffusion tensor imaging was conducted for people with narcolepsy (n = 30) and matched healthy controls as well as symptoms assessment. Structural connectivity for each participant was generated to analyze global and regional topological properties and their correlations with narcoleptic features. Further human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data. RESULTS: A wide and dramatic decrease in structural connectivities was observed in people with narcolepsy, with descending network degree and global efficiency. These metrics were not only correlated with sleep latency and awakening features, but also reflected alterations of sleep macrostructure in people with narcolepsy. Network-based statistics identified a small hyperenhanced subnetwork of cingulate gyrus that was closely related to rapid eye movement sleep behavior disorder (RBD) in narcolepsy. Further imaging genetics analysis suggested glutamatergic signatures were responsible for the preferential vulnerability of connectivity alterations in people with narcolepsy, while additional PET/SPECT data verified that structural alteration was significantly correlated with metabotropic glutamate receptor 5 (mGlutR5) and N-methyl-D-aspartate receptor (NMDA). CONCLUSIONS: People with narcolepsy endured a remarkable decrease in the structural architecture, which was not only closely related to narcolepsy symptoms but also glutamatergic signatures.

Properties of white matter tract diffusivity in children with developmental dyslexia and comorbid attention deficit/hyperactivity disorder.

BACKGROUND: Developmental dyslexia (DD) and attention deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders. Individuals with DD or ADHD have both been shown to have deficits in white matter tracts associated with reading and attentional control networks. However, white matter diffusivity in individuals comorbid with both DD and ADHD (DD + ADHD) has not been specifically explored. METHODS: Participants were 3rd and 4th graders (age range = 7 to 11 years; SD = 0.69) from three diagnostic groups ((DD (n = 40), DD + ADHD (n = 22), and typical developing (TD) (n = 20)). Behavioral measures of reading and attention alongside measures of white matter diffusivity were collected for all participants. RESULTS: DD + ADHD and TD groups differed in mean fractional anisotropy (FA) for the left and right Superior Longitudinal Fasciculus (SLF)-Parietal Terminations and SLF-Temporal Terminations. Mean FA for the DD group across these SLF tracts fell between the lower DD + ADHD and higher TD averages. No differences in mean diffusivity nor significant brain-behavior relations were found. CONCLUSIONS: Findings suggest that WM diffusivity in the SLF increases along a continuum across DD + ADHD, DD, and TD.

SERS "hot spot" enhance-array assay for misfolded SOD1 correlated with white matter lesions and aging.

Misfolding of superoxide dismutase-1 (SOD1) has been correlated with many neurodegenerative diseases, such as Amyotrophic lateral sclerosis's and Alzheimer's among others. However, it is unclear whether misfolded SOD1 plays a role in another neurodegenerative disease of white matter lesions (WMLs). In this study, a sensitive and specific method based on SERS technique was proposed for quantitative detection of misfolded SOD1 content in WMLs. To fabricate the double antibodysandwich substrates for SERS detection, gold nanostars modified with capture antibody were immobilized on glass substrates to prepare active SERS substrates, and then SERS probes conjugated with a Raman reporter and a specific target antibody were coupled with active SERS substrates. This SERS substrates had been employed for quantitative detection of misfolded SOD1 levels in WMLs and exhibited excellent stability, reliability, and accuracy. Moreover, experimental results indicated that the level of misfolded SOD1 increased with the increase in age and the degree of WMLs. Hence, misfolded SOD1 may be a potential blood marker for WMLs and aging. Meanwhile, SERS-based gold nanostars have great clinical application potential in the screening, diagnosis and treatment of WMLs.

Multi-Contrast Magnetic Resonance Imaging of Visual White Matter Pathways in Patients With Glaucoma.

Purpose: Glaucoma is a disorder that involves visual field loss caused by retinal ganglion cell damage. Previous diffusion magnetic resonance imaging (dMRI) studies have demonstrated that retinal ganglion cell damage affects tissues in the optic tract (OT) and optic radiation (OR). However, because previous studies have used a simple diffusion tensor model to analyze dMRI data, the microstructural interpretation of white matter tissue changes remains uncertain. In this study, we used a multi-contrast MRI approach to further clarify the type of microstructural damage that occurs in patients with glaucoma. Methods: We collected dMRI data from 17 patients with glaucoma and 30 controls using 3-tesla (3T) MRI. Using the dMRI data, we estimated three types of tissue property metrics: intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (IsoV). Quantitative T1 (qT1) data, which may be relatively specific to myelin, were collected from all subjects. Results: In the OT, all four metrics showed significant differences between the glaucoma and control groups. In the OR, only the ICVF showed significant between-group differences. ICVF was significantly correlated with qT1 in the OR of the glaucoma group, although qT1 did not show any abnormality at the group level. Conclusions: Our results suggest that, at the group level, tissue changes in OR caused by glaucoma might be explained by axonal damage, which is reflected in the intracellular diffusion signals, rather than myelin damage. The significant correlation between ICVF and qT1 suggests that myelin damage might also occur in a smaller number of severe cases.

Effects of white matter hyperintensities distribution and clustering on late-life cognitive impairment.

White matter hyperintensities (WMH) are a key hallmark of subclinical cerebrovascular disease and are known to impair cognition. Here, we parcellated WMH using a novel system that segments WMH based on both lobar regions and distance from the ventricles, dividing the brain into a coordinate system composed of 36 distinct parcels ('bullseye' parcellation), and then investigated the effect of distribution on cognition using two different analytic approaches. Data from a well characterized sample of healthy older adults (58 to 84 years) who were free of dementia were included. Cognition was evaluated using 12 computerized tasks, factored onto 4 indices representing episodic memory, speed of processing, fluid reasoning and vocabulary. We first assessed the distribution of WMH according to the bullseye parcellation and tested the relationship between WMH parcellations and performance across the four cognitive domains. Then, we used a data-driven approach to derive latent variables within the WMH distribution, and tested the relation between these latent components and cognitive function. We observed that different, well-defined cognitive constructs mapped to specific WMH distributions. Speed of processing was correlated with WMH in the frontal lobe, while in the case of episodic memory, the relationship was more ubiquitous, involving most of the parcellations. A principal components analysis revealed that the 36 bullseye regions factored onto 3 latent components representing the natural aggrupation of WMH: fronto-parietal periventricular (WMH principally in the frontal and parietal lobes and basal ganglia, especially in the periventricular region); occipital; and temporal and juxtacortical WMH (involving WMH in the temporal lobe, and at the juxtacortical region from frontal and parietal lobes). We found that fronto-parietal periventricular and temporal & juxtacortical WMH were independently associated with speed of processing and episodic memory, respectively. These results indicate that different cognitive impairment phenotypes might present with specific WMH distributions. Additionally, our study encourages future research to consider WMH classifications using parcellations systems other than periventricular and deep localizations.