Voxel-based Morphometry Research Articles

Association between vertebral fractures and brain volume: insights from a community cohort study.

Vertebral fractures (VF) due to osteoporosis impact morbidity and quality of life in the elderly. The relationship between VF and changes in brain structure remains underexplored. This study aimed to investigate the association between VF and gray matter volume (GMV) reductions in specific brain regions and to explore potential sex differences. Data from 1,751 participants (571 males, 1,180 females; mean age 64.9, range 18-97) in the fourth survey of the population-based Research on Osteoarthritis/Osteoporosis Against Disability study (2015-2016) were used. Participants were classified into those with and without VF (VF + and VF - groups) based on Genant's semiquantitative method, assessed by spine radiographs. Voxel-based morphometry was applied to MRI images to measure GMV, and a general linear model analysis was performed to compare GMV between groups, adjusting for age, sex, total brain volume, and Mini-Mental State Examination scores as covariates. Additionally, a two-way analysis of variance was conducted on the significant GMV cluster, with sex and VF presence as independent variables, to explore interaction effects. The VF+ group consisted of 113 participants, while the VF- group included 1,638 participants.The analysis identified a significant cluster with reduced GMV in the VF + group compared to the VF - group. This cluster included the right hippocampus, right amygdala, and right parahippocampal gyrus. Further analysis revealed that males in the VF + group exhibited more pronounced GMV reductions in the significant cluster compared to females. These findings suggest that VF is associated with significant reductions in brain regions critical for memory, emotional processing, and visuospatial memory, with more severe effects observed in males.

Suicidal Behaviour Prior to First Episode Psychosis: Wider and More Widespread Grey-Matter Alterations

Introduction The prodromal phase preceding the onset of First Episode Psychosis (FEP) is associated with an increased risk of Suicidal Behaviors (SBs). The aim of this study was to identify specific structural brain abnormalities linked to SBs that occur prior to the onset of FEP. Methods Voxel-based morphometry analyses were used to investigate differences in brain Grey Matter (GM) volume using the CAT12 toolbox within SPM12. Covariates, including gender, age, handedness, intracranial volume, depression severity, and global cognitive functioning, were controlled for as confounding factors. Results Significant reductions in GM were observed in the left superior temporal gyrus, dorsal posterior cingulate cortex, precuneus, cuneus, anterior cerebellum (p-FWE corrected < 0.05, k > 50) as well as in the right amygdala (0.96 ± 0.06 vs. 1.01 ± 0.05; F = 4.78; p < 0.05) and left amygdala (0.97 ± 0.06 vs. 1.02 ± 0.05; F = 8.97; p = 0.01). Conclusions History of SB prior to the onset of the psychotic disorder was related to wider and more widespread brain GM alterations. The regions identified are involved in cognitive and emotional processes such as emotional regulation, social cognition, perseverative thinking, and pain tolerance. These findings suggest that structural brain abnormalities related to SB occurring before FEP onset may serve as early biomarkers for identifying individuals at increased risk of suicide.

Exploring Psychological Factors and Brain Alterations in Functional Anorectal Pain Patients: Insights From Multimodal Magnetic Resonance Imaging Investigations.

Functional anorectal pain (FAP) is classified as one of the disorders of gut-brain interaction (DGBI). It involves the impairments of anorectal afferents and disrupted gut-brain communication. However, neuroimaging studies focused on FAP are lacking. A total of 25 FAP patients and 18 healthy controls (HC) underwent structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), resting-state functional MRI (rs-fMRI) scans, and collection of demographic data, mental health assessment scales and pain assessment questionnaires. Voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), regional homogeneity (ReHo), and amplitude of low-frequency fluctuations (ALFF) were utilized to analyze the imaging data. Correlation analyses were conducted to explore the relationships between the neuroimaging findings and clinical symptoms. Functional anorectal pain (FAP) patients exhibited higher levels of anxiety, depression scores and lower sleep quality compared to HC. VBM analysis revealed increased gray matter volume (GMV) in the bilateral fusiform, right parahippocampal, bilateral inferior temporal gyrus (ITG), and decreased GMV in the right superior frontal gyrus (SFG), left middle frontal gyrus (MFG), bilateral inferior frontal gyrus (IFG), left Calcarine, bilateral middle occipital gyrus (MOG), left middle temporal gyrus (MTG) in FAP patients. TBSS analysis showed decreased fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF), anterior thalamic radiation (ATR), and forceps minor in the FAP patients. Additionally, increased ALFF in the right cerebellum and increased ReHo in the right MFG were observed in the FAP patients. These findings showed a worse psychological condition and suggested neuroanatomical and neurofunctional alterations associated with pain processing, emotion regulation, and cognitive control in FAP patients.

Soluble Aβ pathology predicts neurodegeneration and cognitive decline independently on p-tau in the earliest Alzheimer's continuum: Evidence across two independent cohorts.

Identifying the link between early Alzheimer's disease (AD) pathological changes and neurodegeneration in asymptomatic individuals may lead to the discovery of preventive strategies. We assessed longitudinal brain atrophy and cognitive decline as a function of cerebrospinal fluid (CSF) AD biomarkers in two independent cohorts of cognitively unimpaired (CU) individuals. We used longitudinal voxel-based morphometry (VBM) in combination with hippocampal subfield segmentation. Changes in neuroimaging and cognitive variables were inspected using general linear models (GLMs) adjusting by age, sex, apolipoprotein E (APOE) status, follow-up time, and years of education. In both cohorts, baseline CSF amyloid beta (Aβ) biomarkers significantly predicted medial temporal lobe (MTL) atrophy rates and episodic memory (EM) decline independently of CSF phosphorylated tau (p-tau). Our data suggest that soluble Aβ dyshomeostasis triggers MTL longitudinal atrophy and EM decline independently of CSF p-tau. Our data underscore the need for secondary preventive strategies at the earliest stages of the AD pathological cascade. We assessed brain atrophy and cognitive decline in asymptomatic individuals. Aβ biomarkers predicted MTL atrophy independently of p-tau. Our results underscore the importance of undertaking Alzheimer's preclinical trials.

Voxel-Based Morphometry and Subfield Volumetry Analysis Reveal Limbic System Involvement in Tinnitus.

Tinnitus is a condition in which individuals perceive sounds, such as ringing or buzzing, without any external source. Although the exact cause is not fully understood, recent studies have indicated the involvement of nonauditory brain structures, including the limbic system. We aimed to compare the volumes of specific brain structures between patients with tinnitus and controls. Voxel-based morphometry and subfield volumetry were applied to analyze the brain structures of 53 patients with tinnitus and 52 age- and sex-matched controls. The volumes of the amygdala, hippocampus, and thalamus were measured and compared between the groups. Patients with tinnitus had larger volumes in the whole amygdala, basal nucleus, right lateral nucleus, and left paralaminar nucleus compared with controls. In addition, the subiculum head, left fimbria, and left presubiculum head in the hippocampus were larger in patients with tinnitus. No differences were found in the total thalamic volume or thalamic subnuclei between groups. The gray matter volumes in the thalamus, amygdala, and hippocampus were significantly high in the tinnitus group. The cortical thicknesses of both of the marginal branches of the cingulate sulcus, the left superior parietal lobule, and the left subparietal sulcus were also high in the tinnitus group. These findings indicate the involvement of the limbic system in tinnitus, and enhance our understanding of the condition. The subfield volumetry technique used in this study may aid in identifying the structural differences associated with specific neurological and psychiatric conditions.

Hyperintensity of the left piriform cortex and amygdala on T2-weighted FLAIR images in patients with probable Alzheimer’s disease correlates with cerebral cortical atrophy

Background The left piriform cortex and amygdala (PC&amp;A) tend to be slightly hyperintense relative to the right PC&amp;A on T2-weighted fluid-attenuated inversion recovery (T2W-FLAIR) images in patients with probable Alzheimer’s disease (pAD). This likely represents the antecedent and thus advanced degeneration of the left PC&amp;A. Purpose To investigate the relationship between left PC&amp;A hyperintensities and cerebral cortical atrophy on magnetic resonance (MR) voxel-based morphometry in patients with pAD and discuss how this finding could relate to AD progression. Material and Methods Patients with pAD ( n = 47; age range = 68–93 years, mean = 80.8 ± 6.7 years; 14 men and 33 women) who underwent T2W-FLAIR imaging and MR morphometric study using a voxel-based specific regional analysis system for AD (VSRAD) were retrospectively examined. To measure signal intensity ratios of the left to right PC&amp;A (L-PC&amp;A/R-PC&amp;A), regions of interest (ROIs) were set on the transaxial images in which both PC&amp;As were most broadly depicted; the ROIs were defined as large as possible. Correlations between the L-PC&amp;A/R-PC&amp;A and medial temporal lobe cortical atrophy (MTLCA) as well as whole cerebral cortical atrophy (WCCA) on VSRAD were determined. Correlation between the L-PC&amp;A/R-PC&amp;A and age was also determined. Results The L-PC&amp;A/R-PC&amp;A correlated with both MTLCA (r = 0.375, p = .010, 95% confidence interval [CI] = 0.095–0.600) and WCCA (r = 0.576, p &lt; .001, 95% CI = 0.343–0.742). The L-PC&amp;A/R-PC&amp;A did not correlate with age (r = 0.013, p = .932, 95% CI = −0.282–0.305). Conclusion Left-sided dominance of PC&amp;A degeneration appeared to accelerate with the progression of AD stages.

Sex differences in dorsal striatal volume and interest in quitting smoking.

Over the recent decades, smoking among women has become an increasingly pressing public health challenge. Mounting evidence suggests that, compared to men, women's smoking is more strongly influenced by habitual responses to sensorimotor cues. To understand the brain mechanisms underlying the cessation challenges commonly reported by women who smoke, the present study used voxel-based morphometry (VBM) to investigate sex-related volumetric differences in the dorsal striatum, a region implicated in habitual substance use behavior, and their associations with self-reported quit interest among daily smoking adults. Structural magnetic resonance imaging (MRI) data were collected from 41 women and 52 men (30.1 ± 7.5 years) who reported smoking an average of 15-40 cigarettes per day for at least past 24 months. Multiple regression analyses were carried out with sex and average gray matter volumes (GMV) of predetermined brain regions of interest (ROIs; bilateral caudate, putamen) and control regions (bilateral nucleus accumbens, thalamus) as predictors of self-reported interest in quitting smoking. Women displayed greater striatal GMV and lower current quit interest than men. ROI-based analyses revealed an interaction between sex and putamen GMV, wherein putamen GMV was more strongly and negatively linked to quit interest in women than men. Greater GMV in the putamen could be linked to an attenuated desire to stop smoking among women. This may serve as a neuroanatomical mechanism underlying the higher prevalence of habit-driven smoking behavior observed in women as compared to men.

Medial orbitofrontal cortex structure, function, and cognition associates with weight loss for laparoscopic sleeve gastrectomy.

The objective of this study was to investigate underlying mechanisms of long-term effective weight loss after laparoscopic sleeve gastrectomy (LSG) and effects on the medial orbitofrontal cortex (mOFC) and cognition. A total of 18 individuals with obesity (BMI ≥ 30 kg/m2) underwent LSG. Clinical data, cognitive scores, and brain magnetic resonance imaging scans were evaluated before LSG and 12 months after LSG. We employed voxel-based morphometry analysis and seed-based resting-state functional connectivity (RSFC) analysis to assess LSG-induced structural and functional changes in mOFC. Partial correlation analysis and univariate and multivariate linear regression models were used to explore associations among biochemical indexes, neuroimaging, cognition, and weight loss. No significant improvement in general cognition was found after LSG. Decreases in gray matter volume of the bilateral mOFC and increases in RSFC of the right mOFC were observed 12 months after LSG. Weight loss was associated with RSFC, general cognitive scores, and triglyceride changes. Multivariate linear regression model revealed gray matter volume of the left mOFC and working memory scores at baseline explained 55.2% of the variation in weight loss. These findings suggest that mOFC imaging and cognitive scores could serve as biomarkers for predicting persistent weight loss after LSG, which provides a solid foundation for a potential target for neuromodulation research.

Highly specific amyloid and tau PET ligands for ATN classification in suspected Alzheimer's disease patients.

This study aims to accurately classify ATN profiles using highly specific amyloid and tau PET ligands and MRI in patients with cognitive impairment and suspected Alzheimer's disease (AD). It also aims to explore the relationship between quantified amyloid and tau deposition and cognitive function. Twenty-seven patients (15 women and 12 men; age range: 64-81years) were included in this study. Amyloid and tau PET scans were performed using 18F-NAV4694 and 18F-MK6240, respectively. For each patient, amyloid and tau PET images were visually assessed and classified as either amyloid-positive or amyloid-negative, and as 18F-MK6240 Braak stage 0 (tau-negative) or Braak stages I-VI (tau-positive). Voxel-based morphometry of three-dimensional T1-weighted MRI was used to evaluate neurodegeneration. Amyloid and tau depositions were quantified using the Centiloid scale and standardized uptake value ratio (SUVR), respectively. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Patients were categorized into seven ATN profiles. Six patients (22%) exhibited a normal AD biomarker profile, 15 patients (56%) fell within the Alzheimer's continuum, and 14 patients (52%) were diagnosed with AD. Additionally, six patients (22%) displayed non-AD pathological changes. Positive and negative findings of amyloid and tau PET were concordant in 24 patients (89%). Among the 14 patients diagnosed with AD, the Centiloid scale for amyloid deposition did not show a significant negative correlation with MMSE scores (r = 0.269, p = 0.451). In contrast, the SUVR for tau deposition in the neocortex exhibited a significant negative correlation (r = -0.689, p = 0.014), while tau deposition in the mesial temporal region did not show a significant correlation (r = 0.158, p = 0.763). Highly specific amyloid and tau PET scans, along with MRI, can be utilized to accurately classify ATN profiles in patients with cognitive impairment and suspected AD. The discordance in amyloid and tau PET findings in three patients allowed for a more precise AD diagnosis. Furthermore, tau PET imaging provided insight into the propagation of tau deposition in the neocortex beyond the mesial temporal region, which is associated with cognitive decline.

Neuroanatomical Insights: Convergence and Divergence of Tinnitus with Normal or Mild Hearing Loss

Objectives: To explore the neuroanatomical abnormalities in idiopathic tinnitus patients by voxel-based morphometry (VBM) and surface-based morphometry (SBM) techniques. To elucidate the central plasticity in tinnitus patients with normal or mild hearing loss from the neuroanatomical insights. Methods: A total of 74 patients with idiopathic tinnitus (43 with normal hearing and 31 with mild hearing loss) and 98 healthy subjects were enrolled. VBM and SBM were employed to analyze neuroimaging data and identify neuroanatomical differences. Results: Our analysis revealed a reduction in gray matter volume and a distinctive pattern of changes in cortical surface features in patients with idiopathic tinnitus, especially in brain regions closely related to the limbic system, such as the bilateral parahippocampal gyrus, bilateral entorhinal cortex, and insula. Tinnitus patients with mild hearing loss have more extensive gray matter volume reduction, and more complex changes in cortical surface features compared to tinnitus patients with normal hearing. In addition, we also found a significant correlation between the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), and Montreal Cognitive Assessment (MoCA) scores of patients with idiopathic tinnitus and cortical characteristic parameters in the above brain regions. Conclusions: There are extensive neuroanatomical alterations in tinnitus patients. Mild hearing loss may aggravate the reduction of gray matter volume and change the surface characteristics of the cortex. Anxiety, depression, and cognitive impairment in patients with idiopathic tinnitus may be related to neuroanatomical alterations in specific brain regions.

Atrophy of cerebellum Crus I indicates poor outcome of cochlear implantation in the elderly

Cochlear implantation (CI) is a highly effective treatment for profound hearing loss in elderly individuals, including those with ARHL. However, factors influencing the success of CI in the elderly population are not fully understood. Hence, we sought to investigate the association of regional cerebellar gray matter volume with effectiveness of CI in the elderly. This retrospective cross-sectional study included CI implantees and healthy controls aged ≥ 70 years. We used voxel-based morphometry to investigate the cerebellar gray matter associated with speech perception outcome in the CI group. Among the study participants, cerebellar gray matter volume loss, particularly in the Crus I region, was associated with poorer CI outcomes. Notably, this association was stronger than that observed for the duration of hearing deprivation (DoD). Moreover, the degree of cerebellar atrophy and DoD were found to be independent of each other. No significant correlation was found between the age of the implant and CI outcomes. The findings suggest that cerebellar gray matter atrophy, specifically in the Crus I region, may serve as a predictor of poor outcomes following cochlear implantation in elderly individuals. These results underscore the importance of assessing cerebellar volume loss alongside other factors when counseling elderly patients considering CI.

Early functional and structural hippocampal impairment in a bilateral common carotid artery stenosis mouse model.

Subcortical ischemic vascular dementia (SIVD) is a common subtype of vascular dementia. Currently, the bilateral common carotid artery stenosis (BCAS) mouse model is the most suitable SIVD rodent model. In this study, we investigated the functional and structural impairments in the hippocampus 1 month after BCAS. We used behavioral tests, laser speckle flowmetry, long-term potentiation, histochemical staining, molecular experiments, and voxel-based morphometry to evaluate the hippocampal impairments. Behavioral studies revealed that BCAS mice exhibited worse performance. Laser speckle flowmetry detected an obvious decrease in cerebral blood flow. The synaptic plasticity of the perforant path-dentate gyrus pathway was inhibited. Decreased fractional anisotropy and increased mean diffusivity were detected in the hippocampus via diffusion tensor imaging data. A reduction in gray matter volume, which was most prominent in the hippocampus and its surrounding areas, was detected via voxel-based morphometry analysis. Impairments in cell morphology and myelin integrity were validated using histochemical staining and molecular biology techniques. In addition, the numbers of GFAP+ astrocytes and Iba1+ microglia increased in the hippocampus. Overall, our study demonstrates early functional and structural impairments in the hippocampus contributing to learning and memory deficits after 1 month of BCAS, indicating that the hippocampus is vulnerable to chronic cerebral ischemia.

Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study

BackgroundSpinocerebellar ataxia type 3 (SCA3) is a hereditary disease caused by abnormally expanded CAG repeats in the ATXN3 gene. The study aimed to identify potential biomarkers for assessing therapeutic efficacy by investigating the associations between expanded CAG repeat size, brain and spinal cord volume loss, and motor functions in patients with SCA3.MethodsIn this prospective, cross-observational study, we analyzed 3D T1-weighted MRIs from 92 patients with SCA3 and 42 healthy controls using voxel-based morphometry and region of interest approaches. Associations between expanded CAG repeat size, brain and spinal cord volume loss, and International Cooperative Ataxia Rating Scale (ICARS) scores were investigated using partial correlation and mediation analyses. Sample sizes of potential biomarkers were calculated.ResultsCompared with healthy controls, SCA3 patients had lower cerebellar volume and cervical spinal cord area. SCA3 patients evolved along a stage-independent decline that began in the cerebellum, progressed to spinal cord, brainstem, thalami, and basal ganglia, and extensive subcortex. Expanded CAG repeat size was associated with right cerebellar lobule IV volume (r = − 0.423, P < 0.001) and cervical spinal cord area (r = − 0.405, P < 0.001), and higher ICARS (r = 0.416, P < 0.001). Mediation analysis revealed an indirect effect of expanded CAG repeat size on ICARS through spinal cord. Sample sizes estimation revealed that a minimum sample size was achieved with spinal cord measures.ConclusionsOur results indicate the potential of cervical spinal cord area as a biomarker for disease progression and a minimum sample size estimation in future clinical studies of SCA3.

Comparative analysis of Voxel-based morphometry using T1 and T2-weighted magnetic resonance imaging to explore the relationship between brain structure and cognitive abilities.

Voxel-based morphometry (VBM) of T1-weighted (T1-w) magnetic resonance imaging (MRI) is primarily used to study the association of brain structure with cognitive functions. However, in theory, T2-weighted (T2-w) MRI could also be used in VBM studies because of its sensitivity to pathology and tissue changes. We aimed to compare the T1-w and T2-w images to study brain structures in association with cognitive abilities. VBM analysis was applied to T1-w and T2-w MRI data of 120 healthy participants aged 20 to 40. The MRI data was collected using a 3T machine, and it was analyzed with CAT12 to extract maps of Gray matter(GM). We used six cognitive tasks to assess cognitive abilities, including the balloon analog risk task (BART), block design, forward and backward digit span (FDST and BDST), and trail-making tasks A and B. Compared to T2-w, T1-w data showed more brain voxels in the BART, block design, FDST, TMT-A, and TMT-B tasks. However, T2-w imaging identified a greater number of voxels in the BDST. T1-w images identified more correlated brain regions with cognitive scores in the FDST, TMT-A, and B tasks than T2-w. In BART and Block design tasks, both methods revealed the same number of correlated regions, and T2-w just showed more regions than T1-w in the BDST. Findings revealed distinct patterns of sensitivity between T1-w and T2-w imaging in detecting brain regions associated with cognition. The two approaches demonstrated different strengths in identifying areas correlated with cognitive abilities. This study provides valuable guidance for selecting appropriate methods for identifying the optimal approach for detecting brain regions that exhibit the strongest correlations with cognitive abilities.

Changes in the Parietal Lobe Subregion Volume at Various Stages of Alzheimer's Disease and the Role in Cognitively Normal and Mild Cognitive Impairment Conversion.

Volume alterations in the parietal subregion have received less attention in Alzheimer's disease (AD), and their role in predicting conversion of mild cognitive impairment (MCI) to AD and cognitively normal (CN) to MCI remains unclear. In this study, we aimed to assess the volumetric variation of the parietal subregion at different cognitive stages in AD and to determine the role of parietal subregions in CN and MCI conversion. We included 662 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, including 228 CN, 221 early MCI (EMCI), 112 late MCI (LMCI), and 101 AD participants. We measured the volume of the parietal subregion based on the Human Brainnetome Atlas (BNA-246) using voxel-based morphometry among individuals at various stages of AD and the progressive and stable individuals in CN and MCI. We then calculated the area under the curve (AUC) of the receiver operating characteristic (ROC) curve to test the ability of parietal subregions to discriminate between different cognitive groups. The Cox proportional hazard model was constructed to determine which specific parietal subregions, alone or in combination, could be used to predict progression from MCI to AD and CN to MCI. Finally, we examined the relationship between the cognitive scores and parietal subregion volume in the diagnostic groups. The left inferior parietal lobule (IPL)_6_5 (rostroventral area 39) showed the best ability to discriminate between patients with AD and those with CN (AUC = 0.688). The model consisting of the left IPL_6_4 (caudal area 40) and bilateral IPL_6_5 showed the best combination for predicting the CN progression to MCI. The left IPL_6_1 (caudal area 39) showed the best predictive power in predicting the progression of MCI to AD. Certain subregions of the volume correlated with cognitive scales. Subregions of the angular gyrus are essential in the early onset and subsequent development of AD, and early detection of the volume of these regions may be useful in identifying the tendency to develop the disease and its treatment.

Disrupted Paraventricular Hypothalamic Nucleus Functional Connectivity in Parkinson's Disease With Constipation.

Constipation is one of the most common non-motor symptoms in patients with Parkinson's disease (PD), which could manifest during the early stage of the disease. However, the etiology of constipation in PD remains largely unknown. Previous studies supported that gastrointestinal dysfunction may be associated with functional connectivity alterations in paraventricular hypothalamic nucleus (PVN). Therefore, this study aimed to investigate the potential contribution of the PVN to the pathogenesis of constipation in a cohort of early-stage patients with PD and to compare brain network organization between PD patients with and without constipation. A total of 66 PD patients (PD with constipation and without constipation) and 30 healthy controls were prospectively enrolled. All participants acquired T1-weighted and resting-state fMRI scans. Then we employed voxel-based morphometry analysis and functional connectivity analysis. We observed a decreased functional connectivity in the PVN-pontine tegmentum pathway in PD patients with constipation compared to the patients without constipation (p = 0.006, t = 5.37), while we did not find any changes in basal ganglia circuitry between these two groups. In addition, we found that the functional connectivity between PVN and pontine tegmentum was negatively associated with the UPDRS I, II, III and NMSS scores (p < 0.05). Meanwhile, these two types of patients also showed substantial differences in functional connections linking the inferior frontal gyrus and cerebellum with multiple brain regions. We discovered no statistical difference in gray matter volume among these two groups. Our study provides further insights into the dysfunctional mechanisms of constipation, suggesting that abnormal PVN functional connectivity may be related to the mechanism of constipation in PD. Meanwhile, the inferior frontal gyrus and cerebellum may be involved in the occurrence of constipation in PD patients.

Microstructural and functional connectivity changes of decision-related brain networks in end-stage kidney disease patients undergoing peritoneal dialysis.

We aimed to explore changes in decision-related brain microstructure, brain functional activities, and functional connectivity, and their correlations with cognitive function in end-stage kidney disease (ESKD) patients undergoing peritoneal dialysis (PD). Furthermore, the impact of dialysis on these changes was examined. Thirty ESKD patients undergoing PD, 20 chronic kidney disease (CKD) stage 5 patients without dialysis (predialysis CKD stage 5), and 30 healthy controls (HC) were recruited for the study. Various assessments have been conducted, including neuropsychological scale testing, decision-related behavioral tests, voxel-based morphometry, and functional magnetic resonance imaging. Compared to the HC group, PD patients showed decreased functional activation and gray matter volume in multiple decision-related brain areas, including the ventromedial prefrontal cortex (vmPFC), orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC) (p < 0.05, false discovery rate-corrected). The default mode network (DMN) and salience network (SAN) were the primary brain regions that showed decreased functional connectivity to the vmPFC and ACC. Additionally, compared to the predialysis group, the PD group showed enhanced brain activation in decision-related brain regions such as the ACC, vmPFC, and insula. Though PD and predialysis CKD stage 5 patients performed poorly in the neuropsychological and Iowa Gambling Task (IGT), there was no significant difference between the two groups. The structure and function variabilities of the vmPFC were correlated with IGT and Montreal Cognitive Assessment score, and the activation of OFC was negatively associated with blood creatinine, cystatin, and parathyroid hormone levels. In summary, PD can change the structure and function of decision-related brain circuits (vmPFC-OFC-ACC) and reduce integration within DMN and SAN, which is correlated with cognitive function and clinical features. Moreover, our findings may suggest the comparable capability of PD in preserving one's cognitive function and disease progression. Multimodal neuroimaging based on structure and function can provide more objective information for the early diagnosis and intervention of cognitive impairment in ESKD patients.

Clinical validation of artificial intelligence-based single-subject morphometry without normative reference database.

Single-subject voxel-based morphometry (VBM) is a powerful technique for reader-independent detection of brain atrophy in structural magnetic resonance imaging (MRI) to support the (differential) diagnosis and staging of neurodegenerative diseases in individual patients. However, VBM is sensitive to the MRI scanner platform and details of the acquisition sequence. To mitigate this limitation, we recently proposed and technically validated a convolutional neural network (CNN)-based VBM which does not rely on a normative reference database. Clinical validation of CNN-based VBM. CNN-based VBM was compared with conventional VBM based on a mixed-scanner normative database in 227 consecutive patients (66.0 ± 9.6 years, 53.3% female) with suspected dementing neurodegenerative disease. VBM maps were interpreted visually by two experienced readers, first with respect to the presence of any neurodegenerative disease, then for the differentiation between Alzheimer's disease (AD)-typical and non-AD atrophy patterns. A Likert 6-score was used for both tasks. Simultaneously acquired positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) served as reference standard. Repeated-measures ANOVA revealed a significant impact of the VBM method on the visual detection of any neurodegenerative disease (p < 0.001). Balanced accuracy/sensitivity/specificity were 80.4/86.3/74.5% for CNN-based VBM versus 75.7/79.5/71.8% for conventional VBM. Differentiation between AD and non-AD typical atrophy patterns did not differ between both VBM methods (p = 0.871). CNN-based VBM provides clinically useful accuracy for the detection of neurodegeneration-suspect atrophy with higher sensitivity than conventional VBM with a mixed-scanner normative reference database and without compromising specificity.

Assessment of complementary white matter microstructural changes and grey matter atrophy in the 6-OHDA-induced model of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by motor symptoms such as tremors, rigidity, and bradykinesia. Magnetic resonance imaging (MRI) offers a non-invasive means to study PD and its progression. This study utilized the unilateral 6-hydroxydopamine (6-OHDA) rat model of parkinsonism to assess whether white matter microstructural integrity measured using advanced free-water diffusion tensor imaging metrics (fw-DTI) and gray matter density using voxel-based morphometry (VBM) can serve as imaging biomarkers of pathological changes following nigrostriatal denervation. By comparing the 6-OHDA-lesioned vs. sham-lesioned rats, we aimed to identify complementary gray matter and white matter changes indicative of disease pathophysiology. Results showed widespread gray matter atrophy and subtle changes in white matter integrity in the 6-OHDA lesioned rats. Gray matter atrophy predominantly affected ipsilateral cortical regions, with some bilateral regions also showing atrophy. Conversely, higher volumes were observed in some regions of the contralateral gray matter in the 6-OHDA model. Furthermore, increased fw-FA and fw-AX were observed in regions including the brainstem, thalamus, superior and inferior colliculus, and fornix. Smaller clusters of decreased fw-FA and fw-AX were found in the corpus callosum. Regions of both increased and decreased diffusivity were noted in fw-RD, primarily in the brainstem, while the f index was elevated in several regions in the 6-OHDA lesioned group, except for a cluster in the contralateral thalamus. In conclusion, this study underscores the significant potential role for gray and white matter imaging biomarkers in delineating disease pathology in parkinsonism.

Neuropathological contributions to grey matter atrophy and white matter hyperintensities in amnestic dementia

BackgroundDementia patients commonly present multiple neuropathologies, worsening cognitive function, yet structural neuroimaging signatures of dementia have not been positioned in the context of combined pathology. In this study, we implemented an MRI voxel-based approach to explore combined and independent effects of dementia pathologies on grey and white matter structural changes.MethodsIn 91 amnestic dementia patients with post-mortem brain donation, grey matter density and white matter hyperintensity (WMH) burdens were obtained from pre-mortem MRI and analyzed in relation to Alzheimer’s, vascular, Lewy body, TDP-43, and hippocampal sclerosis (HS) pathologies. After exploring co-occurrence profiles of these pathologies, voxel-based morphometry was implemented to determine their joint and independent effects on grey matter loss. The impact of these pathologies on WMH burden was then evaluated both in spatial and quantitative combined analyses, using voxel-based and generalized linear models respectively.Results86.8% of patients in this cohort presented more than one pathology. The combined structural effect of these pathologies was a focal impact on hippocampal grey matter atrophy, primarily driven by HS and Alzheimer’s pathology (family-wise error corrected, p < 0.05), which also exhibited the strongest individual effects (uncorrected, p < 0.001). WMHs, predominant in middle and anterior cerebral portions, were most strongly associated with vascular (T = 2.47, p = 0.017) and tau pathologies (T = 2.09, p = 0.041).ConclusionsThe mixed associations of these dementia neuroimaging hallmarks are relevant for the fine-tuning of diagnostic protocols and underscore the need for comprehensive pathology evaluations in the study of dementia phenotypes.