Disrupted dynamic amplitude of low-frequency fluctuations in patients with active thyroid-associated ophthalmopathy.

Purpose: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease that affects the orbit and is the most prevalent extra-thyroidal complication of Graves' disease. Previous neuroimaging studies have focused on abnormal static regional activity and functional connectivity in patients with TAO. However, the characteristics of local brain activity over time are poorly understood. This study aimed to investigate alterations in the dynamic amplitude of low-frequency fluctuation (dALFF) in patients with active TAO and to distinguish patients with TAO from healthy controls (HCs) using a support vector machine (SVM) classifier. Methods: A total of 21 patients with TAO and 21 HCs underwent resting-state functional magnetic resonance imaging scans. dALFFs were calculated in conjunction with sliding window approaches to assess dynamic regional brain activity and to compare the groups. Then, we used SVM, a machine learning algorithm, to determine whether dALFF maps may be used as diagnostic indicators for TAO. Results: Compared with HCs, patients with active TAO showed decreased dALFF in the right calcarine, lingual gyrus, superior parietal lobule, and precuneus. The SVM model showed an accuracy of 45.24%-47.62% and area under the curve of 0.35-0.44 in distinguishing TAO from HCs. No correlation was found between clinical variables and regional dALFF. Conclusion: Patients with active TAO showed altered dALFF in the visual cortex and the ventral and dorsal visual pathways, providing further details on the pathogenesis of TAO.

Disrupted voxel-mirrored homotopic connectivity in congenital nystagmus using resting-state fMRI.

OBJECTIVES: Idiopathic congenital nystagmus (CN) is a rare eye disease that can cause early blindness (EB). CN deficits are observed most frequently with oculomotor dysfunction; however, it is still unclear what neuromechanics underly CN with EB. Based on that visual experience requires the functional integration of both hemispheres, we hypothesized that CN adolescents with EB might exhibit impaired interhemispheric synchrony. Our study aimed to investigate the interhemispheric functional connectivity alterations using voxel-mirrored homotopic connectivity (VMHC) and their relationships with clinical features in CN patients. MATERIALS AND METHODS: This study included 21 patients with CN and EB, and 21 sighted controls (SC), who were matched for sex, age and educational level. The 3.0 T MRI scan and ocular examination were performed. The VMHC differences were examined between the two groups, and the relationships between mean VMHC values in altered brain regions and clinical variables in the CN group were evaluated by Pearson correlation analysis. RESULTS: Compared with the SC group, the CN had increased VMHC values in the bilateral cerebellum posterior and anterior lobes/cerebellar tonsil/declive/pyramis/culmen/pons, middle frontal gyri (BA 10) and frontal eye field/superior frontal gyri (BA 6 and BA 8). No particular areas of the brain had lower VMHC values. Furthermore, no correlation with the duration of disease or blindness could be demonstrated in CN. CONCLUSION: Our results suggest the existence of interhemispheric connectivity changes and provide further evidence for the neurological basis of CN with EB.

Alterations of voxel-wise spontaneous activity and corresponding brain functional networks in multiple system atrophy patients with mild cognitive impairment.

Emerging evidence has indicated that cognitive impairment is an underrecognized feature of multiple system atrophy (MSA). Mild cognitive impairment (MCI) is related to a high risk of dementia. However, the mechanism underlying MCI in MSA remains controversial. In this study, we conducted the amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) analyses to detect the characteristics of local neural activity and corresponding network alterations in MSA patients with MCI (MSA-MCI). We enrolled 80 probable MSA patients classified as cognitively normal (MSA-NC, n = 36) and MSA-MCI (n = 44) and 40 healthy controls. Compared with MSA-NC, MSA-MCI exhibited decreased ALFF in the right dorsal lateral prefrontal cortex (RDLPFC) and increased ALFF in the right cerebellar lobule IX and lobule IV-V. In the secondary FC analyses, decreased FC in the left inferior parietal lobe (IPL) was observed when we set the RDLPFC as the seed region. Decreased FC in the bilateral cuneus, left precuneus, and left IPL and increased FC in the right middle temporal gyrus were shown when we set the right cerebellar lobule IX as the seed region. Furthermore, FC of DLPFC-IPL and cerebello-cerebral circuit, as well as ALFF alterations, were significantly correlated with Montreal Cognitive Assessment scores in MSA patients. We also employed whole-brain voxel-based morphometry analysis, but no gray matter atrophy was detected between the patient subgroups. Our findings indicate that altered spontaneous activity in the DLPFC and the cerebellum and disrupted DLPFC-IPL, cerebello-cerebral networks are possible biomarkers of early cognitive decline in MSA patients.

Alterations of brain activity in multiple system atrophy patients with freezing of gait: A resting-state fMRI study.

Background: Freezing of gait (FOG) in multiple system atrophy (MSA) is characterized by a higher risk of falls and a reduced quality of life; however, the mechanisms underlying these effects have yet to be identified by neuroimaging. The aim of this study was to investigate the differences in functional network when compared between MSA patients with and without freezing. Methods: Degree centrality (DC) based on the resting-state functional magnetic resonance imaging was computed in 65 patients with MSA and 36 healthy controls. Brain regions with statistically different DC values between groups were selected as seed points for a second seed-based functional connectivity (FC) analysis. The relationships between brain activity (DC and FC alterations) and the severity of freezing symptoms were then investigated in the two groups of patients with MSA. Results: Compared to MSA patients without FOG symptoms (MSA-nFOG), patients with MSA-FOG showed an increased DC in the left middle temporal gyrus but a reduced DC in the right superior pole temporal gyrus, left anterior cingulum cortex, left thalamus, and right middle frontal gyrus. Furthermore, in patients with MSA-FOG, the DC in the left thalamus was negatively correlated with FOG scores. Using the left thalamus as a seed, secondary seed-based functional connectivity analysis revealed that patients with MSA-FOG commonly showed the left thalamus-based FC abnormalities in regions related to cognition and emotion. In contrast to the patients with MSA-nFOG, patients with MSA-FOG showed an increased FC between the left thalamus and the left middle temporal gyrus (MTG), right inferior parietal lobule (IPL), bilateral cerebellum_8, and left precuneus. Conclusion: Freezing of gait is associated with centrality of the impaired thalamus network. Abnormal FC between the thalamus and left MTG, right IPL, bilateral cerebellum_8, and left precuneus was involved in FOG. These results provide new insight into the pathophysiological mechanism of FOG in MSA.

Alteration of Degree Centrality in Adolescents With Early Blindness.

Congenital nystagmus in infants and young children can lead to early blindness (EB). Previous neuroimaging studies have demonstrated that EB is accompanied by alterations in brain structure and function. However, the effects of visual impairment and critical developmental periods on brain functional connectivity at rest have been unclear. Here, we used the voxel-wise degree centrality (DC) method to explore the underlying functional network brain activity in adolescents with EB. Twenty-one patients with EBs and 21 sighted controls (SCs) underwent magnetic resonance imaging. Differences between the two groups were assessed using the DC method. Moreover, the support vector machine (SVM) method was used to differentiate patients with EB patients from the SCs according to DC values. Compared with the SCs, the patients with EB had increased DC values in the bilateral cerebellum_6, cerebellum vermis_4_5, bilateral supplementary motor areas (SMA), and left fusiform gyrus; the patients with EB had decreased DC values in the bilateral rectal gyrus and left medial orbital frontal gyrus. The SVM classification of the DC values achieved an overall accuracy of 70.45% and an area under the curve of 0.86 in distinguishing between the patients with EB and the SCs. Our study may reveal the neuromechanism of neuroplasticity in EB; the findings provide an imaging basis for future development of restorative visual therapies and sensory substitution devices, and future assessments of visual rehabilitation efficacy.

Freezing of Gait in Multiple System Atrophy.

Background and Purpose: Freezing of gait (FOG) is a common gait disturbance phenomenon in multiple system atrophy (MSA) patients. The current investigation assessed the incidence FOG in a cross-sectional clinical study, and clinical correlations associated with it. Methods: Ninety-nine MSA patients from three hospitals in China were consecutively enrolled in the study. Eight patients were subsequently excluded from the analysis due to incomplete information. The prevalence of FOG symptoms in the MSA cohort was determined, and clinical manifestations in MSA patients with and without FOG were assessed. Results: Of 91 MSA patients, 60 (65.93%) exhibited FOG. The incidence of FOG increased with disease duration and motor severity and was correlated with modified Hoehn and Yahr (H-Y) stages [odds ratio (OR), 0.54; 95% confidence interval (CI), 0.33-3.92], longer disease duration (OR, 0.54, 95% CI, 0.37-0.78), higher Unified Multiple System Atrophy Rating Scale (UMSARS) score (OR, 0.96, 95% CI, 0.93-0.99), MSA-cerebellum subtype (OR, 2.99, 95% CI, 1.22-7.33), levodopa-equivalent dose (LDED) (OR, 0.998, 95% CI, 0.997-1.00), and higher Scale for the Assessment and Rating of Ataxia (SARA) score (OR, 0.80, 95% CI, 0.72-0.89) (logistic regression). Motor dysfunction was significantly positively associated with lower quality of life scores (p < 0.01). Conclusion: FOG is a common symptom in MSA patients and it is correlated with poor quality of life, disease progression and severity, levodopa-equivalent dose, and cerebellum impairment.

Surface modification of polytetrafluoroethylene (PTFE) with a heparin-immobilized extracellular matrix (ECM) coating for small-diameter vascular grafts applications.

Intimal hyperplasia, thrombosis formation, and delayed endothelium regeneration are the main causes that restrict the clinical applications of PTFE small-diameter vascular grafts (inner diameter < 6 mm). An ideal strategy to solve such problems is to facilitate in situ endothelialization. Since the natural vascular endothelium adheres onto the basement membrane, which is a specialized form of extracellular matrix (ECM) secreted by endothelial cells (ECs) and smooth muscle cells (SMCs), functionalizing PTFE with an ECM coating was proposed. However, besides ECs, the ECM-modified PTFE improved SMC growth as well, thereby increasing the risk of intimal hyperplasia. In the present study, heparin was immobilized on the ECM coating at different densities (4.89 ± 1.02 µg/cm2, 7.24 ± 1.56 µg/cm2, 15.63 ± 2.45 µg/cm2, and 26.59 ± 3.48 µg/cm2), aiming to develop a bio-favorable environment that possessed excellent hemocompatibility and selectively inhibited SMC growth while promoting endothelialization. The results indicated that a low heparin density (4.89 ± 1.02 µg/cm2) was not enough to restrict platelet adhesion, whereas a high heparin density (26.59 ± 3.48 µg/cm2) resulted in decreased EC growth and enhanced SMC proliferation. Therefore, a heparin density at 7.24 ± 1.56 µg/cm2 was the optimal level in terms of antithrombogenicity, endothelialization, and SMC inhibition. Collectively, this study proposed a heparin-immobilized ECM coating to modify PTFE, offering a promising means to functionalize biomaterials for developing small-diameter vascular grafts.

Altered resting-state functional network connectivity in profound sensorineural hearing loss infants within an early sensitive period: A group ICA study.

Data from both animal models and deaf children provide evidence for that the maturation of auditory cortex has a sensitive period during the first 2-4 years of life. During this period, the auditory stimulation can affect the development of cortical function to the greatest extent. Thus far, little is known about the brain development trajectory after early auditory deprivation within this period. In this study, independent component analysis (ICA) technique was used to detect the characteristics of brain network development in children with bilateral profound sensorineural hearing loss (SNHL) before 3 years old. Seven resting-state networks (RSN) were identified in 50 SNHL and 36 healthy controls using ICA method, and further their intra-and inter-network functional connectivity (FC) were compared between two groups. Compared with the control group, SNHL group showed decreased FC within default mode network, while enhanced FC within auditory network (AUN) and salience network. No significant changes in FC were found in the visual network (VN) and sensorimotor network (SMN). Furthermore, the inter-network FC between SMN and AUN, frontal network and AUN, SMN and VN, frontal network and VN were significantly increased in SNHL group. The results implicate that the loss and the compensatory reorganization of brain network FC coexist in SNHL infants. It provides a network basis for understanding the brain development trajectory after hearing loss within early sensitive period.

Morphological Changes in Cortical and Subcortical Structures in Multiple System Atrophy Patients With Mild Cognitive Impairment.

OBJECTIVE: This study aimed to investigate the morphometric alterations in the cortical and subcortical structures in multiple system atrophy (MSA) patients with mild cognitive impairment (MCI), and to explore the association with cognitive deficits. METHODS: A total of 45 MSA patients (25 MSA-only, 20 MSA-MCI) and 29 healthy controls were recruited. FreeSurfer software was used to analyze cortical thickness, and voxel-based morphometry was used to analyze the gray matter volumes. Cortical thickness and gray matter volume changes were correlated with cognitive scores. RESULTS: Compared to healthy controls, both MSA subgroups exhibited widespread morphology alterations of brain structures in the fronto-temporal regions. Direct comparison of MSA-MCI and MSA-only patients showed volume reduction in the left superior and middle temporal gyrus, while cortical thinning was found in the left middle and inferior temporal gyrus in MSA-MCI patients. Cortical thinning in the left middle temporal gyrus correlated with cognitive assessment and disease duration. CONCLUSION: Structural changes in the brain occur in MSA-MCI patients. The alteration of brain structure in the left temporal regions might be a biomarker of cognitive decline in MSA-MCI patients.

MRI-Based Radiomics of Basal Nuclei in Differentiating Idiopathic Parkinson's Disease From Parkinsonian Variants of Multiple System Atrophy: A Susceptibility-Weighted Imaging Study.

OBJECTIVES: To investigate the value of MRI-based radiomic model based on the radiomic features of different basal nuclei in differentiating idiopathic Parkinson's disease (IPD) from Parkinsonian variants of multiple system atrophy (MSA-P). METHODS: Radiomics was applied to the 3T susceptibility- weighted imaging (SWI) from 102 MSA-P patients and 83 IPD patients (allocated to a training and a testing cohort, 7:3 ratio). The substantia nigra (SN), caudate nucleus (CN), putamen (PUT), globus pallidus (GP), red nucleus (RN), and subthalamic nucleus (STN) were manually segmented, and 396 features were extracted. After feature selection, support vector machine (SVM) was generated, and its predictive performance was calculated in both the training and testing cohorts using the area under receiver operating characteristic curve (AUC). RESULTS: Seven radiomic features were selected from the PUT, by which the SVM classifier achieved the best diagnostic performance with an AUC of 0.867 in the training cohort and an AUC of 0.862 in the testing cohort. Furthermore, the combined model, which incorporating part III of the Parkinson's Disease Rating Scale (UPDRSIII) scores into radiomic features of the PUT, further improved the diagnostic performance. However, radiomic features extracted from RN, SN, GP, CN, and STN had moderate to poor diagnostic performance, with AUC values that ranged from 0.610 to 0.788 in the training cohort and 0.583 to 0.766 in the testing cohort. CONCLUSION: Radiomic features derived from the PUT had optimal value in differentiating IPD from MSA-P. A combined radiomic model, which contained radiomic features of the PUT and UPDRSIII scores, further improved performance and may represent a promising tool for distinguishing between IPD and MSA-P.

Alterations in Degree Centrality and Functional Connectivity in Parkinson's Disease Patients With Freezing of Gait: A Resting-State Functional Magnetic Resonance Imaging Study.

OBJECTIVE: Freezing of gait (FOG) is a common disabling motor symptom in Parkinson's disease (PD), but the potential pathogenic mechanisms are still unclear. METHODS: A total of 22 patients with PD with FOG (PD-FOG), 28 patients with PD without FOG (PD-nFOG), and 33 healthy controls (HCs) were recruited in this study. Degree centrality (DC)-a graph theory-based measurement of global connectivity at the voxel level by measuring the number of instantaneous functional connections between one region and the rest of the brain-can map brain hubs with high sensitivity, specificity, and reproducibility. DC was used to explore alterations in the centrality of PD-FOG correlated with brain node levels. PD-FOG cognitive network dysfunction was further revealed via a seed-based functional connectivity (FC) analysis. In addition, correlation analyses were carried out between clinical symptoms and acquired connectivity measurement. RESULTS: Compared to the PD-nFOG group, the PD-FOG group showed remarkably increased DC values in the right middle frontal gyrus (RMFG). There were no significant differences in other gray matter regions. Importantly, the clinical severity of FOG was related to the mean DC values in the RMFG. This brain region served as a seed in secondary seed-based FC analysis, and we further found FC changes in the right precuneus, right inferior frontal gyrus, right superior frontal gyrus (SFG), and cerebellum. CONCLUSION: Increased RMFG activity and FC network alterations in the middle frontal cortex with the precuneus, inferior, and SFG, and the cerebellum may have great potential in brain dysfunction in PD with FOG.

Altered resting-state voxel-level whole-brain functional connectivity in multiple system atrophy patients with cognitive impairment.

OBJECTIVE: There is increasing evidence of cognitive impairment (CI) frequently occurring in patients with multiple system atrophy (MSA); however, the neurobiological mechanisms underlying CI in patients with MSA remain unclear. METHODS: We enrolled 61 patients with probable MSA and 33 healthy controls (HC). We used degree centrality (DC) analysis to assess changes in the centrality level of MSA-CI related brain nodes. We conducted a secondary seed-based functional connectivity (FC) analysis to investigate dysfunctions in cognitive networks related to MSA. Further, we analysed the correlation between clinical symptoms and acquired connectivity measures. RESULTS: Compared with HC, patients with MSA-CI and those with MSA with normal cognition (MSA-NCI) exhibited lower DC values in the left calcarine and right postcentral regions and higher DC values in the bilateral caudate and left precuneus. There were significant differences in the DC values in the right middle prefrontal gyrus between the MSA-CI and MSA-NCI groups. The mean DC values in the right middle prefrontal gyrus (RMPFG) were correlated with clinical cognitive severity. Consequently, we used this brain region as a seed in secondary seed-based FC analysis and observed FC changes within the right precuneus, inferior parietal lobe, and right insula. CONCLUSIONS: Decreased middle prefrontal cortex activity and its altered functional connectivity with the precuneus, inferior parietal lobe, and insula are possible biomarkers of cognitive dysfunction in patients with MSA-CI. SIGNIFICANCE: Cognitive impairment in MSA is associated with alterations in the dorsolateral prefrontal cortex network.

Cerebellar atrophy and its contribution to motor and cognitive performance in multiple system atrophy.

OBJECTIVE: Neuroanatomical differences in the cerebellum are among the most consistent findings in multiple system atrophy (MSA) patients. This study performed a detailed cerebellar morphology in MSA patients and its two subtypes: MSA-P (parkinson's symptoms predominate) and MSA-C (cerebellar symptoms predominant), and their relations to profiles of motor and cognitive deficits. MATERIALS AND METHODS: Structure MRI data were acquired from 63 healthy controls and 61 MSA patients; voxel-based morphometry and the Spatially Unbiased Infratentorial Toolbox cerebellar atlas were performed to identify the cerebellar gray volume changes in MSA and its subtypes. Further, the gray matter changes were correlated with the clinical motor/cognitive scores. RESULTS: Patients with MSA exhibited widespread loss of cerebellar volume bilaterally, relative to healthy controls. In those with MSA-C, gray matter loss was detected from anterior (bilateral lobule IV-V) to posterior (bilateral crus I/II, bilateral lobule IX, left lobule VIII) cerebellar lobes. Lower anterior cerebellar volume negatively correlated with disease duration and motor performance, whereas posterior lobe integrity positively correlated with cognitive assessment. In patients with MSA-P, atrophy of anterior lobe (bilateral lobules IV-V) and posterior lobe in part (left lobule VI, bilateral IX) was evident; and in left cerebellar lobule IX, gray matter loss negatively correlated with motor scores. Direct comparison of MSA-P and MSA-C group outcomes showed divergence in right cerebellar crus II only. CONCLUSIONS: Our data suggest that volumetric abnormalities of cerebellum contribute substantially to motor and cognitive performance in patients with MSA. In patients with MSA-P and MSA-C, affected regions of cerebellum differed.

Alterations of structural and functional connectivity in profound sensorineural hearing loss infants within an early sensitive period: A combined DTI and fMRI study.

Due to heightened level of neuroplasticity, there is a sensitive period (2-4 years after birth) that exists for optimal central auditory development. Using diffusion tensor imaging combined with resting-state functional connectivity (rsFC) analysis, this study directly investigates the structural connectivity alterations of the whole brain white matter (WM) and the functional reorganization of the auditory network in infants with sensorineural hearing loss (SNHL) during the early sensitive period. 46 bilateral profound SNHL infants prior to cochlear implantation (mean age, 17.59 months) and 33 healthy controls (mean age, 18.55 months) were included in the analysis. Compared with controls, SNHL infants showed widespread WM alterations, including bilateral superior longitudinal fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, right corticospinal tract, posterior thalamic radiation and left uncinate fasciculus. Moreover, SNHL infants demonstrated increased rsFC between left/right primary auditory cortex seeds and right insula and superior temporal gyrus. In conclusion, this study suggests that SNHL in the early sensitive period is associated with diffuse WM alterations that mainly affect the auditory and language pathways. Furthermore, increased rsFC in areas mainly associated with auditory and language networks may potentially reflect reorganization and compensatory activation in response to auditory deprivation during the early sensitive period.

Altered functional connectivity of dentate nucleus in parkinsonian and cerebellar variants of multiple system atrophy.

The cerebellum is known to influence cerebral cortical activity via cerebello-thalamo-cortical (CTC) circuits and thereby may be implicated in the pathophysiology of multiple system atrophy (MSA). As the aim of this study, we investigated the abnormalities of corticocerebellar functional connectivity (FC) in patients with two variants of MSA. Resting-state functional magnetic resonance imaging (rs-fMRI) studies were obtained from 55 patients with MSA, including Parkinsonian (MSAp, n = 29) and cerebellar (MSAc, n = 26) variants. We also examined a similar number of healthy controls (HC, n = 51). Seed-based connectivity analysis was performed to assess alterations in CTC circuits. Relations between FC and clinical scores were assessed as well. Compared with the HC group, diminished FC was evident from bilateral dentate nucleus (DN) to motor cortex, bilateral basal ganglia, right cerebellum, default mode network (DMN), and limbic system in patients with MSAc. Patients with MSAp (vs HC subjects) showed less FC from left DN to right putamen, DMN, and limbic systems. Reduced FC was also demonstrated from left DN to DMN in patients with MSAc (vs MSAp), as well as from right DN to right cerebellum, DMN, basal ganglia, motor cortex, and limbic systems. In addition, the extent of FC from right DN to right cerebellum negatively correlated with Unified Parkinson's Disease Rating Scale-III scores in patients with MSA, while showing a positive association with Montreal Cognitive Assessment scores. The FC of DN was similarly altered in patients with MSAc and MSAp, although right cerebellar and motor cortical changes were more widespread in the MSAc group. There may be differing mechanisms of cerebellar functional activity responsible for motor and cognitive impairment, which should be further investigated.

Do multiple system atrophy and Parkinson's disease show distinct patterns of volumetric alterations across hippocampal subfields? An exploratory study.

OBJECTIVES: To investigate the volumetric alterations of hippocampal subfields and identify which subfields contribute to mild cognitive impairment (MCI) in multiple system atrophy (MSA) and Parkinson's disease (PD). METHODS: Thirty MSA-MCI, 26 PD-MCI, and 30 healthy controls were administered cognitive assessment, along with hippocampal segmentation using FreeSurfer 6.0 after a 3-T MRI scan. Regression analyses were performed between the volumes of hippocampal subfields and cognitive variables. RESULTS: Compared with healthy controls, the volume of the hippocampal fissure was enlarged in PD-MCI patients, while left Cornu Ammonis (CA2-CA3), bilateral molecular layer, bilateral hippocampus-amygdala transition area, right subiculum, right CA1, right presubiculum, right parasubiculum, and bilateral whole hippocampus were reduced in the MSA-MCI group. Moreover, volumetric reductions of the bilateral hippocampal tail, bilateral CA1, bilateral presubiculum, bilateral molecular layer, left CA2-CA3, left hippocampus-amygdala transition area, right parasubiculum, and bilateral whole hippocampus were found in MSA-MCI relative to the PD-MCI group. The volumes of the left CA2-CA3 (B = - 11.34, p = 0.006) and left parasubiculum (B = 4.63, p = 0.01) were respectively correlated with language and abstraction functions. The volumes of the left fimbria (B = 6.99, p = 0.002) and left hippocampus-amygdala transition area (B = 2.28, p = 0.009) were correlated with visuospatial/executive function. CONCLUSIONS: The MSA-MCI patients showed more widespread impairment of hippocampal subfields compared with the PD-MCI group, involving trisynaptic loop and amygdala-hippocampus interactions. The alteration of CA, hippocampus-amygdala transition area, and fimbria still requires further comparison between the two patient groups. KEY POINTS: • The atrophy patterns of hippocampal subfields differed between MSA and PD patients. • MSA has widespread change in trisynaptic loop and amygdala-hippocampus interactions. • The atrophy patterns may help to understand the differences of cognitive impairment in MSA and PD.

Similarities and differences in cerebellar grey matter volume and disrupted functional connectivity in idiopathic Parkinson's disease and multiple system atrophy.

OBJECTIVE: This study investigated the potential differences in changes to cerebellar grey matter volume (GMV) and functional connectivity (FC) and the association between them, which might elucidate cerebellar function in multiple system atrophy (MSA) and idiopathic Parkinson's disease (IPD). METHODS: Resting-state functional magnetic resonance imaging and three-dimensional T1 scans were obtained from 38 IPD, 62 MSA, and 59 healthy controls (HC). Seed-based connectivity analysis and voxel-based morphometry analysis were performed to assess the changes of cerebellar FC and GMV between the patient groups. RESULT: Decreased cerebellar GMV was found in the motor cerebellum in both patient groups relative to HC, and broader reduction of GMV was observed in both cognitive and motor cerebellum in MSA compared with IPD and HC. Compared with IPD, the MSA group exhibited decreased FC between bilateral dentate nucleus (DN) and default mode network (DMN). Decreased intracerebellar FC was observed in both patient groups relative to HC. Cerebellar GMV was positively correlated with FC of intracerebellum and DN-DMN in MSA. Motor/cognitive scores were associated with DN-DMN FC, with considerable cerebellar GMV loss in MSA patients. CONCLUSION: Cerebellar GMV loss and cerebellar FC alterations showed similarities in IPD and MSA, along with more widespread changes to GMV in motor and cognitive cerebellum and altered DN-DMN FC in MSA. Further research is needed to better describe the alterations of cerebellar GMV in the cognitive cerebellum and association between cerebellar GMV and intracerebellar FC during the early stages of MSA and IPD.

Comparing abnormalities of amplitude of low-frequency fluctuations in multiple system atrophy and idiopathic Parkinson's disease measured with resting-state fMRI.

Multiple system atrophy (MSA) and Idiopathic Parkinson's disease (IPD) show overlapping clinical manifestations with different treatment and prognosis. However, the shared and distinct underlying neural substrates are not yet understood, which needs to be explored between MSA and IPD. Resting-state functional magnetic resonance imaging data were collected from 29 MSA patients, 17 IPD patients and 25 healthy controls (HC) and the Amplitude of Low-Frequency Fluctuations (ALFF) was compared. Lower ALFF in bilateral basal ganglion, bilateral ventrolateral prefrontal cortex and right amygdala, as well as higher ALFF in parieto-temporo-occipital cortex and right cerebellum was shared between both patient groups to compare with HC. In contrast to IPD, decreased or increased ALFF in different regions of visual associative cortices and decreased ALFF in right cerebellum were found in MSA group. Our findings suggested shared and distinct spontaneous brain activity abnormalities in striato-thalamo-cortical (STC) loop, default mood network, visual associative cortices and cerebellum were present in MSA and IPD, which may help to explain similar clinical symptoms in both disorders but a more severe illness prognosis in MSA. Further research is needed to better describe the functional role of the cerebellum and visual associative cortices in early stages of MSA and IPD.

Using 'swallow-tail' sign and putaminal hypointensity as biomarkers to distinguish multiple system atrophy from idiopathic Parkinson's disease: A susceptibility-weighted imaging study.

OBJECTIVE: To investigate the value of 'swallow-tail' sign and putaminal hypointensity on 3 T susceptibility-weighted imaging (SWI) for distinguishing multiple system atrophy (MSA) from idiopathic Parkinson's disease (IPD). METHODS: Three groups - 39 MSA patients, 18 IPD patients,and 31 healthy controls (HCs) - were administered a 3 T SWI sequence to evaluate 'swallow-tail' sign and putaminal hypointensity using visual scales from 0 to 2 and 0 to 3 scores, respectively. The diagnostic accuracy of the two signs separately and combined was calculated using a receiver operating characteristic curve, with clinical diagnosis as the gold standard. RESULTS: The scores of 'swallow-tail' sign were lower in IPD than in MSA or in HCs, as well as for putaminal hypointensity in IPD or HCs than in MSA (p < 0.05). The sensitivity and specificity of 'swallow-tail' sign and putaminal hypointensity were 87.9% and 83.3%, and 35.9% and 100%, respectively, in the respective patient groups. The area under the curve of combined signs was increased from 0.85 ('swallow tail') or 0.68 (putaminal hypointensity) to 0.93. CONCLUSION: The combination of 'swallow-tail' sign and putaminal hypointensity can increase the accuracy of discriminating between MSA and IPD. KEY POINTS: • Differential diagnosis of MSA and IPD is still challenging in clinical practice. • Absence of 'swallow-tail' sign is a valuable biomarker for IPD on SWI. • Putaminal hypointensity is a valuable biomarker for MSA on SWI. • Combined 'swallow- tail' sign and putaminal hypointensity increase diagnostic accuracy.