Neuroimage-Clinical最新文献

Objective

The pathogenesis of depression in patients with Parkinson’s disease (PD) is poorly understood. Therefore, this study aimed to explore the changes in γ-aminobutyric acid (GABA) and glutamate plus glutamine (Glx) levels in patients with PD with or without depression determined using MEscher-GArwood Point Resolved Spectroscopy (MEGA-PRESS).

Materials and methods

A total of 83 patients with primary PD and 24 healthy controls were included. Patients with PD were categorized into depressed PD (DPD, n = 19) and nondepressed PD (NDPD, n = 64) based on the 17-item Hamilton Depression Rating Scale. All participants underwent T1-weighted imaging and MEGA-PRESS sequence to acquire GABA+ and Glx values. The MEGA-PRESS sequence was conducted using 18.48 mL voxels in the left thalamus and medial frontal cortex. The GABA+, Glx, and creatine values were quantified using Gannet 3.1 software.

Results

The GABA+ and Glx values were not significantly disparate between patients with PD and controls in the thalamus and medial frontal cortex. However, the levels of N-acetyl aspartate/creatine and choline/creatine in the left thalamus were significantly lower in patients with PD than in controls (P = .031, P = .009). The GABA+/Water and GABA+/Creatine in the medial frontal cortex were higher in DPD than in NDPD (P = .001, P = .004). The effects of depression on Glx or other metabolite levels were not evident, and no significant difference in metabolite values was noted in the left thalamus among all groups (P > .05).

Conclusions

GABA+ levels increased in the medial frontal cortex in DPD, which may be more closely related to depressive pathology. Thus, alterations in GABAergic function in special brain structures may be related to the clinical manifestations of PD symptoms, and hence mediating this function might help in treating depression in PD.

Introduction

AD and CVD, which frequently co-occur, are leading causes of age-related cognitive decline. We assessed how demographic factors, socioeconomic status (SES) as indicated by education and occupation, vascular risk factors, and a range of biomarkers associated with both CVD (including white matter hyperintensities [WMH], diffusion MRI abnormalities, infarctions, and microbleeds) and AD (comprising amyloid-PET and tau-PET) collectively influence cognitive function.

Methods

In this cross-sectional population study, structural equation models were utilized to understand these associations in 449 participants (mean age (SD) = 74.5 (8.4) years; 56% male; 7.5% cognitively impaired).

Results

(1) Higher SES had a protective effect on cognition with mediation through the vascular pathway. (2) The effect of amyloid directly on cognition and through tau was 11-fold larger than the indirect effect of amyloid on cognition through WMH. (3) There is a significant effect of vascular risk on tau deposition.

Discussion

The utilized biomarkers captured the impact of CVD and AD on cognition. The overall effect of vascular risk and SES on these biomarkers are complex and need further investigation.

Cushing’s disease (CD) represents a state of cortisol excess, serving as a model to investigate the effects of prolonged hypercortisolism on functional brain. Potential alterations in the functional connectome of the brain may explain frequently reported cognitive deficits and affective disorders in CD patients. This study aims to elucidate the effects of chronic hypercortisolism on the principal functional gradient, which represents a hierarchical architecture with gradual transitions across cognitive processes, by integrating connectomics and transcriptomics approaches. Utilizing resting-state functional magnetic resonance imaging data from 140 participants (86 CD patients, 54 healthy controls) recruited at a single center, we explored the alterations in the principal gradient in CD patients. Further, we thoroughly explored the underlying associative mechanisms of the observed characteristic alterations with cognitive function domains, biological attributes, and neuropsychiatric representations, as well as gene expression profiles. Compared to healthy controls, CD patients demonstrated changes in connectome patterns in both primary and higher-order networks, exhibiting an overall converged trend along the principal gradient axis. The gradient values in CD patients’ right prefrontal cortex and bilateral sensorimotor cortices exhibited a significant correlation with cortisol levels. Moreover, the cortical regions showing gradient alterations were principally associated with sensory information processing and higher-cognitive functions, as well as correlated with the gene expression patterns which involved synaptic components and function. The findings suggest that converged alterations in the principal gradient in CD patients may mediate the relationship between hypercortisolism and cognitive impairments, potentially involving genes regulating synaptic components and function.

Objective

Aneurysmal subarachnoid hemorrhage (aSAH) and angiographically negative subarachnoid hemorrhage (anSAH) cause an abrupt rise in intracranial pressure, resulting in shearing forces, causing damage to the white matter tracts. This study aims to investigate whole-brain white matter abnormalities with diffusion kurtosis imaging (DKI) after both aSAH and anSAH and explores whether these abnormalities are associated with impaired cognitive functioning.

Methods

Five months post-ictus, 34 patients with aSAH, 24 patients with anSAH and 17 healthy controls (HC) underwent DKI MRI scanning and neuropsychological assessment (measuring verbal memory, psychomotor speed, executive control, and social cognition). Differences in DKI measures (fractional anisotropy, mean diffusivity, axial diffusivity [AD], radial diffusivity, and mean kurtosis) were examined using tract-based spatial statistics. Significant voxel masks were then correlated with neuropsychological scores.

Results

All DKI measures differed significantly between patients with aSAH and HC, but no significant differences were found between patients with anSAH and HC. Although the two SAH groups did not differ significantly on all DKI parameters, effect sizes indicated that the anSAH group might be more similar to HC. Cognitive impairments were found for both SAH groups relative to HC. No significant associations were found between these impairments and white matter abnormalities in the aSAH group, but lower psychomotor speed scores were associated with higher AD values (r = -0.41, p = 0.04) in patients with anSAH.

Conclusions

Patients with aSAH showed significant white matter diffusion abnormalities, while the anSAH group, despite cognitive deficits, did not. However, there were no significant differences between the SAH groups, and no correlations between DKI metrics and cognitive measures, except for one test on psychomotor speed in the anSAH group. Overall, this study suggests that while anSAH may not be as severe as aSAH, it is still not a benign condition. Further research with larger anSAH cohorts is necessary to gain a more precise understanding of white matter injuries, particularly regarding their prevalence.

Introduction

Brain viscoelasticity as assessed by magnetic resonance elastography (MRE) has been discussed as a promising surrogate of microstructural alterations due to neurodegenerative processes. Existing studies indicate that multiple sclerosis (MS) is associated with a global reduction in brain stiffness. However, no study to date systematically investigated the MS-related characteristics of brain viscoelasticity separately in normal-appearing white matter (NAWM), deep gray matter (DGM) and T2-hyperintense white matter (WM) lesions.

Methods

70 MS patients and 42 healthy volunteers underwent whole-cerebral MRE using a stimulated echo sequence (DENSE) with a low-frequency mechanical excitation at 20 Hertz. The magnitude $\left|G^{\ast }\right|$ (Pa) and phase angle $\phi$ (rad) of the complex shear modulus $G^{\ast }$ were reconstructed by multifrequency dual elasto-visco (MDEV) inversion and related to structural imaging and clinical parameters.

Results

We observed $\phi$ in the thalamus to be higher by 4.3 % in patients relative to healthy controls (1.11 ± 0.07 vs. 1.06 ± 0.07, p < 0.0001). Higher Expanded Disability Status Scale (EDSS) scores were negatively associated with $\phi$ in the basal ganglia (p = 0.01). We measured $\phi$ to be lower in MS lesions compared to surrounding NAWM (p = 0.001), which was most prominent for lesions in the temporal lobe (1.01 ± 0.22 vs. 1.06 ± 0.19, p = 0.003). Age was associated with lower values of $|G^{\ast }|$ (p = 0.04) and $\phi$ (p = 0.004) in the thalamus of patients. No alteration in NAWM stiffness relative to WM in healthy controls was observed.

Conclusion

Low-frequency elastography in MS patients reveals age-independent alterations in the viscoelasticity of deep gray matter at early stages of disease.

Objective

Benign childhood epilepsy with centrotemporal spikes (BECTS) affects brain network hierarchy and cognitive function; however, it remains unclear how hierarchical change affects cognition in patients with BECTS. A major aim of this study was to examine changes in the macro-network function hierarchy in BECTS and its potential contribution to cognitive function.

Methods

Overall, the study included 50 children with BECTS and 69 healthy controls. Connectome gradient analysis was used to determine the brain network hierarchy of each group. By comparing gradient scores at each voxel level and network between groups, we assessed changes in whole-brain voxel-level and network hierarchy. Functional connectivity was used to detect the functional reorganization of epilepsy caused by these abnormal brain regions based on these aberrant gradients. Lastly, we explored the relationships between the change gradient and functional connectivity values and clinical variables and further predicted the cognitive function associated with BECTS gradient changes.

Results

In children with BECTS, the gradient was extended at different network and voxel levels. The gradient scores frontoparietal network was increased in the principal gradient of patients with BECTS. The left precentral gyrus (PCG) and right angular gyrus gradient scores were significantly increased in the principal gradient of children with BECTS. Moreover, in regions of the brain with abnormal principal gradients, functional connectivity was disrupted. The left PCG gradient score of children with BECTS was correlated with the verbal intelligence quotient (VIQ), and the disruption of functional connectivity in brain regions with abnormal principal gradients was closely related to cognitive function. VIQ was significantly predicted by the principal gradient map of patients.

Significance

The results indicate connectome gradient disruption in children with BECTS and its relationship to cognitive function, thereby increasing our understanding of the functional connectome hierarchy and providing potential biomarkers for cognitive function of children with BECTS.

Longitudinal hippocampal atrophy is commonly used as progressive marker assisting clinical diagnose of dementia. However, precise quantification of the atrophy is limited by longitudinal segmentation errors resulting from MRI artifacts across multiple independent scans. To accurately segment the hippocampal morphology from longitudinal 3T T1-weighted MR images, we propose a diffeomorphic geodesic guided deep learning method called the GeoLongSeg to mitigate the longitudinal variabilities that unrelated to diseases by enhancing intra-individual morphological consistency. Specifically, we integrate geodesic shape regression, an evolutional model that estimates smooth deformation process of anatomical shapes, into a two-stage segmentation network. We adopt a 3D U-Net in the first-stage network with an enhanced attention mechanism for independent segmentation. Then, a hippocampal shape evolutional trajectory is estimated by geodesic shape regression and fed into the second network to refine the independent segmentation. We verify that GeoLongSeg outperforms other four state-of-the-art segmentation pipelines in longitudinal morphological consistency evaluated by test–retest reliability, variance ratio and atrophy trajectories. When assessing hippocampal atrophy in longitudinal data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), results based on GeoLongSeg exhibit spatial and temporal local atrophy in bilateral hippocampi of dementia patients. These features derived from GeoLongSeg segmentation exhibit the greatest discriminatory capability compared to the outcomes of other methods in distinguishing between patients and normal controls. Overall, GeoLongSeg provides an accurate and efficient segmentation network for extracting hippocampal morphology from longitudinal MR images, which assist precise atrophy measurement of the hippocampus in early stage of dementia.

Over the past decades, morphometric analysis of brain MRI has contributed substantially to the understanding of healthy brain structure, development and aging as well as to improved characterisation of disease related pathologies. Certified commercial tools based on normative modeling of these metrics are meanwhile available for diagnostic purposes, but they are cost intensive and their clinical evaluation is still in its infancy. Here we have compared the performance of “ScanOMetrics”, an open-source research-level tool for detection of statistical anomalies in individual MRI scans, depending on whether it is operated on the output of FreeSurfer or of the deep learning based brain morphometry tool DL + DiReCT. When applied to the public OASIS3 dataset, containing patients with Alzheimer’s disease (AD) and healthy controls (HC), cortical thickness anomalies in patient scans were mainly detected in regions that are known as predilection areas of cortical atrophy in AD, regardless of the software used for extraction of the metrics. By contrast, anomaly detections in HCs were up to twenty-fold reduced and spatially unspecific using both DL + DiReCT and FreeSurfer. Progression of the atrophy pattern with clinical dementia rating (CDR) was clearly observable with both methods. DL + DiReCT provided results in less than 25 min, more than 15 times faster than FreeSurfer. This difference in computation time might be relevant when considering application of this or similar methodology as diagnostic decision support for neuroradiologists.

Diminished basal parasympathetic nervous system activity is a feature of frontotemporal dementia that relates to left frontoinsula dysfunction and empathy impairment. Individuals with a pathogenic expansion of the hexanucleotide repeat in chromosome 9 open reading frame 72 (C9orf72), the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis, provide a unique opportunity to examine whether parasympathetic activity is disrupted in genetic forms of frontotemporal dementia and to investigate when parasympathetic deficits manifest in the pathophysiological cascade. We measured baseline respiratory sinus arrhythmia, a parasympathetic measure of heart rate variability, over two minutes in a sample of 102 participants that included 19 asymptomatic expansion carriers (C9⁺ asymp), 14 expansion carriers with mild cognitive impairment (C9⁺ MCI), 16 symptomatic expansion carriers with frontotemporal dementia (C9⁺ FTD), and 53 expansion-negative healthy controls (C9^- HC) who also underwent structural magnetic resonance imaging. In follow-up analyses, we compared baseline respiratory sinus arrhythmia in the C9⁺ FTD group with an independent age-, sex-, and clinical severity-matched group of 26 people with sporadic behavioral variant frontotemporal dementia. The Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating-Sum of Boxes score was used to quantify behavioral symptom severity, and informant ratings on the Interpersonal Reactivity Index provided measures of participants’ current emotional (empathic concern) and cognitive (perspective-taking) empathy. Results indicated that the C9⁺ FTD group had lower baseline respiratory sinus arrhythmia than the C9⁺ MCI, C9⁺ asymp, and C9^- HC groups, a deficit that was comparable to that of sporadic behavioral variant frontotemporal dementia. Linear regression analyses indicated that lower baseline respiratory sinus arrhythmia was associated with worse behavioral symptom severity and lower empathic concern and perspective-taking across the C9orf72 expansion carrier clinical spectrum. Whole-brain voxel-based morphometry analyses in participants with C9orf72 pathogenic expansions found that lower baseline respiratory sinus arrhythmia correlated with smaller gray matter volume in the left frontoinsula and bilateral thalamus, key structures that support parasympathetic function, and in the bilateral parietal lobes, occipital lobes, and cerebellum, regions that are also vulnerable in individuals with C9orf72 expansions. This study provides novel evidence that basal parasympathetic functioning is diminished in FTD due to C9orf72 expansions and suggests that baseline respiratory sinus arrhythmia may be a potential non-invasive biomarker that is sensitive