Structural connectivity from DTI to predict mild cognitive impairment in de novo Parkinson's disease.

BACKGROUND: Early detection of Parkinson's disease (PD) patients at high risk for mild cognitive impairment (MCI) can help with timely intervention. White matter structural connectivity is considered an early and sensitive indicator of neurodegenerative disease. OBJECTIVES: To investigate whether baseline white matter structural connectivity features from diffusion tensor imaging (DTI) of de novo PD patients can help predict PD-MCI conversion at an individual level using machine learning methods. METHODS: We included 90 de novo PD patients who underwent DTI and 3D T1-weighted imaging. Elastic net-based feature consensus ranking (ENFCR) was used with 1000 random training sets to select clinical and structural connectivity features. Linear discrimination analysis (LDA), support vector machine (SVM), K-nearest neighbor (KNN) and naïve Bayes (NB) classifiers were trained based on features selected more than 500 times. The area under the ROC curve (AUC), accuracy (ACC), sensitivity (SEN) and specificity (SPE) were used to evaluate model performance. RESULTS: A total of 57 PD patients were classified as PD-MCI nonconverters, and 33 PD patients were classified as PD-MCI converters. The models trained with clinical data showed moderate performance (AUC range: 0.62-0.68; ACC range: 0.63-0.77; SEN range: 0.45-0.66; SPE range: 0.64-0.84). Models trained with structural connectivity (AUC range, 0.81-0.84; ACC range, 0.75-0.86; SEN range, 0.77-0.91; SPE range, 0.71-0.88) performed similar to models that were trained with both clinical and structural connectivity data (AUC range, 0.81-0.85; ACC range, 0.74-0.85; SEN range, 0.79-0.91; SPE range, 0.70-0.89). CONCLUSIONS: Baseline white matter structural connectivity from DTI is helpful in predicting future MCI conversion in de novo PD patients.

Abnormal functional connectivity density involvement in freezing of gait and its application for subtyping Parkinson's disease.

The pathophysiological mechanisms at work in Parkinson's disease (PD) patients with freezing of gait (FOG) remain poorly understood. Functional connectivity density (FCD) could provide an unbiased way to analyse connectivity across the brain. In this study, a total of 23 PD patients with FOG (PD FOG + patients), 26 PD patients without FOG (PD FOG- patients), and 22 healthy controls (HCs) were recruited, and their resting-state functional magnetic resonance imaging (rs-fMRI) images were collected. FCD mapping was first performed to identify differences between groups. Pearson correlation analysis was used to explore relationships between FCD values and the severity of FOG. Then, a machine learning model was employed to classify each pair of groups. PD FOG + patients showed significantly increased short-range FCD in the precuneus, cingulate gyrus, and fusiform gyrus and decreased long-range FCD in the frontal gyrus, temporal gyrus, and cingulate gyrus. Short-range FCD values in the middle temporal gyrus and inferior temporal gyrus were positively correlated with FOG questionnaire (FOGQ) scores, and long-range FCD values in the middle frontal gyrus were negatively correlated with FOGQ scores. Using FCD in abnormal regions as input, a support vector machine (SVM) classifier can achieve classification with good performance. The mean accuracy values were 0.895 (PD FOG + vs. HC), 0.966 (PD FOG- vs. HC), and 0.897 (PD FOG + vs. PD FOG-). This study demonstrates that PD FOG + patients showed altered short- and long-range FCD in several brain regions involved in action planning and control, motion processing, emotion, cognition, and object recognition.

Dysfunction of human brain network hierarchy in Parkinson's disease patients with freezing of gait.

INTRODUCTION: Hierarchy has been identified as a principle underlying the organization of human brain networks. In Parkinson's disease with freezing of gait (PD-FOG), it remains unclear whether and how the network hierarchy is disrupted. Additionally, the associations between changes in the brain network hierarchy of PD patients with FOG and clinical scales remain unclear. The aim of this study was to explore alterations in the network hierarchy of PD-FOG and their clinical relevance. METHODS: In this study, the brain network hierarchy of each group was described through a connectome gradient analysis among 31 PD-FOG, 50 PD patients without FOG (PD-NFOG), and 38 healthy controls (HC). Changes in the network hierarchy were assessed by comparing different gradient values of each network between the PD-FOG, PD-NFOG and HC groups. We further examined the relationship between dynamically changing network gradient values and clinical scales. RESULTS: For the second gradient, Salience/ventral attention network-A (SalVentAttnA) network gradient of PD-FOG group was significantly lower than that of PD-NFOG, while both PD subgroups had a Default mode network-C gradient that was significantly lower than that of the HC group. In the third gradient, somatomotor network-A gradient of PD-FOG patients was significantly lower than the PD-NFOG group. Moreover, reduced SalVentAttnA network gradient values were associated with more severe gaits, fall risk, and frozen gait in PD-FOG patients. CONCLUSIONS: The brain network hierarchy in PD-FOG is disturbed, this dysfunction is related to the severity of frozen gait. This study provides novel evidence for the neural mechanisms of FOG.

Aberrant degree centrality of functional brain networks in subclinical depression and major depressive disorder.

Background: As one of the most common diseases, major depressive disorder (MDD) has a significant adverse impact on the li of patients. As a mild form of depression, subclinical depression (SD) serves as an indicator of progression to MDD. This study analyzed the degree centrality (DC) for MDD, SD, and healthy control (HC) groups and identified the brain regions with DC alterations. Methods: The experimental data were composed of resting-state functional magnetic resonance imaging (rs-fMRI) from 40 HCs, 40 MDD subjects, and 34 SD subjects. After conducting a one-way analysis of variance, two-sample t-tests were used for further analysis to explore the brain regions with changed DC. Receiver operating characteristic (ROC) curve analysis of single index and composite index features was performed to analyze the distinguishable ability of important brain regions. Results: For the comparison of MDD vs. HC, increased DC was found in the right superior temporal gyrus (STG) and right inferior parietal lobule (IPL) in the MDD group. For SD vs. HC, the SD group showed a higher DC in the right STG and the right middle temporal gyrus (MTG), and a smaller DC in the left IPL. For MDD vs. SD, increased DC in the right middle frontal gyrus (MFG), right IPL, and left IPL, and decreased DC in the right STG and right MTG was found in the MDD group. With an area under the ROC (AUC) of 0.779, the right STG could differentiate MDD patients from HCs and, with an AUC of 0.704, the right MTG could differentiate MDD patients from SD patients. The three composite indexes had good discriminative ability in each pairwise comparison, with AUCs of 0.803, 0.751, and 0.814 for MDD vs. HC, SD vs. HC, and MDD vs. SD, respectively. Conclusion: Altered DC in the STG, MTG, IPL, and MFG were identified in depression groups. The DC values of these altered regions and their combinations presented good discriminative ability between HC, SD, and MDD. These findings could help to find effective biomarkers and reveal the potential mechanisms of depression.

Baseline cerebral structural morphology predict freezing of gait in early drug-naïve Parkinson's disease.

Freezing of gait (FOG) greatly impacts the daily life of patients with Parkinson's disease (PD). However, predictors of FOG in early PD are limited. Moreover, recent neuroimaging evidence of cerebral morphological alterations in PD is heterogeneous. We aimed to develop a model that could predict the occurrence of FOG using machine learning, collaborating with clinical, laboratory, and cerebral structural imaging information of early drug-naïve PD and investigate alterations in cerebral morphology in early PD. Data from 73 healthy controls (HCs) and 158 early drug-naïve PD patients at baseline were obtained from the Parkinson's Progression Markers Initiative cohort. The CIVET pipeline was used to generate structural morphological features with T1-weighted imaging (T1WI). Five machine learning algorithms were calculated to assess the predictive performance of future FOG in early PD during a 5-year follow-up period. We found that models trained with structural morphological features showed fair to good performance (accuracy range, 0.67-0.73). Performance improved when clinical and laboratory data was added (accuracy range, 0.71-0.78). For machine learning algorithms, elastic net-support vector machine models (accuracy range, 0.69-0.78) performed the best. The main features used to predict FOG based on elastic net-support vector machine models were the structural morphological features that were mainly distributed in the left cerebrum. Moreover, the bilateral olfactory cortex (OLF) showed a significantly higher surface area in PD patients than in HCs. Overall, we found that T1WI morphometric markers helped predict future FOG occurrence in patients with early drug-naïve PD at the individual level. The OLF exhibits predominantly cortical expansion in early PD.

Diffusion Tensor Imaging Analysis Along the Perivascular Space Index in Primary Parkinson's Disease Patients With and Without Freezing of Gait.

Parkinson's disease (PD) is a common neurodegeneration disease associated with the abnormal deposition and spread of misfolded proteins (α-synuclein and Tau protein), which progressively damages the glymphatic system. This research intended to investigate the activity of the glymphatic system in PD individuals with freezing of gait (PD-FOG) and PD patients without it (PD-nFOG), as well as their relationship to the clinical neural scale. Diffusion tensor imaging (DTI) was performed in 28 PD-FOG individuals, 31 PD-nFOG individuals, and 34 healthy controls (HC). The DTI analysis along the perivascular space (DTI-ALPS) index was computed after post-processing of DTI images, representing brain glymphatic functions. The DTI-ALPS index was assessed for the association with the clinical variables. Compared to the HC group, the DTI-ALPS index of both PD-FOG and PD-nFOG patients was significantly decreased; however, no notable difference was found between the PD-FOG and PD-nFOG group. In addition, the DTI-ALPS index of PD-nFOG patients were positively correlated with disease duration, Unified Parkinson's Disease Rating-III Right (UPDRS-III R), UPDRS-III TOTAL, UPDRS-IV. Taken together, these findings highlighted the weakening of function of the glymphatic system in PD individuals, which is associated with motor symptoms and treatment complications. We speculate that treatment aimed at enhancing the flow and clearance of the glymphatic system may alleviate clinical symptoms of PD.

Alterations of functional connectivity of the lateral habenula in subclinical depression and major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a common cause of disability and morbidity, affecting about 10% of the population worldwide. Subclinical depression (SD) can be understood as a precursor of MDD, and therefore provides an MDD risk indicator. The pathogenesis of MDD and SD in humans is still unclear, and the current diagnosis lacks accurate biomarkers and gold standards. METHODS: A total of 40 MDD, 34 SD, and 40 healthy control (HC) participants matched by age, gender, and education were included in this study. Resting-state functional magnetic resonance images (rs-fMRI) were used to analyze the functional connectivity (FC) of the posterior parietal thalamus (PPtha), which includes the lateral habenula, as the region of interest. Analysis of variance with the post hoc t-test test was performed to find significant differences in FC and clarify the variations in FC among the HC, SD, and MDD groups. RESULTS: Increased FC was observed between PPtha and the left inferior temporal gyrus (ITG) for MDD versus SD, and between PPtha and the right ITG for SD versus HC. Conversely, decreased FC was observed between PPtha and the right middle temporal gyrus (MTG) for MDD versus SD and MDD versus HC. The FC between PPtha and the middle frontal gyrus (MFG) in SD was higher than that in MDD and HC. Compared with the HC group, the FC of PPtha-ITG (left and right) increased in both the SD and MDD groups, PPtha-MTG (right) decreased in both the SD and MDD groups and PPtha-MFG (right) increased in the SD group and decreased in the MDD group. CONCLUSION: Through analysis of FC measured by rs-fMRI, the altered FC between PPtha and several brain regions (right and left ITG, right MTG, and right MFG) has been identified in participants with SD and MDD. Different alterations in FC between PPtha and these regions were identified for patients with depression. These findings might provide insights into the potential pathophysiological mechanisms of SD and MDD, especially related to PPtha and the lateral habenula.

Disrupted Brain Structural Network Connection in de novo Parkinson's Disease With Rapid Eye Movement Sleep Behavior Disorder.

Objective: To explore alterations in white matter network topology in de novo Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD). Materials and Methods: This study included 171 de novo PD patients and 73 healthy controls (HC) recruited from the Parkinson's Progression Markers Initiative (PPMI) database. The patients were divided into two groups, PD with probable RBD (PD-pRBD, n = 74) and PD without probable RBD (PD-npRBD, N = 97), according to the RBD screening questionnaire (RBDSQ). Individual structural network of brain was constructed based on deterministic fiber tracking and analyses were performed using graph theory. Differences in global and nodal topological properties were analyzed among the three groups. After that, post hoc analyses were performed to explore further differences. Finally, correlations between significant different properties and RBDSQ scores were analyzed in PD-pRBD group. Results: All three groups presented small-world organization. PD-pRBD patients exhibited diminished global efficiency and increased shortest path length compared with PD-npRBD patients and HCs. In nodal property analyses, compared with HCs, the brain regions of the PD-pRBD group with changed nodal efficiency (Ne) were widely distributed mainly in neocortical and paralimbic regions. While compared with PD-npRBD group, only increased Ne in right insula, left middle frontal gyrus, and decreased Ne in left temporal pole were discovered. In addition, significant correlations between Ne in related brain regions and RDBSQ scores were detected in PD-pRBD patients. Conclusions: PD-pRBD patients showed disrupted topological organization of white matter in the whole brain. The altered Ne of right insula, left temporal pole and left middle frontal gyrus may play a key role in the pathogenesis of PD-RBD.

Structural Brain Network Abnormalities in Parkinson's Disease With Freezing of Gait.

Objective: Diffusion tensor imaging (DTI) studies have investigated white matter (WM) integrity abnormalities in Parkinson's disease (PD). However, little is known about the topological changes in the brain network. This study aims to reveal these changes by comparing PD without freezing of gait (FOG) (PD FOG-), PD with FOG (PD FOG+), and healthy control (HC). Methods: 21 PD FOG+, 34 PD FOG-, and 23 HC were recruited, and DTI images were acquired. The graph theoretical analysis and network-based statistical method were used to calculate the topological parameters and assess connections. Results: PD FOG+ showed a decreased normalized clustering coefficient, small-worldness, clustering coefficient, and increased local network efficiency compared with HCs. PD FOG+ showed decreased centrality, degree centrality, and nodal efficiency in the striatum, frontal gyrus, and supplementary motor area (SMA). PD FOG+ showed decreased connections in the frontal gyrus, cingulate gyrus, and caudate nucleus (CAU). The between centrality of the left SMA and left CAU was negatively correlated with FOG questionnaire scores. Conclusion: This study demonstrates that PD FOG+ exhibits disruption of global and local topological organization in structural brain networks, and the disrupted topological organization can be potential biomarkers in PD FOG+. These new findings may provide increasing insight into the pathophysiological mechanism of PD FOG+.

Altered Degree Centrality of Brain Networks in Parkinson's Disease With Freezing of Gait: A Resting-State Functional MRI Study.

Freezing of gait (FOG) in Parkinson's disease (PD) leads to devastating consequences; however, little is known about its functional brain network. We explored the differences in degree centrality (DC) of functional networks among PD with FOG (PD FOG+), PD without FOG (PD FOG-), and healthy control (HC) groups. In all, 24 PD FOG+, 37 PD FOG-, and 22 HCs were recruited and their resting-state functional magnetic imaging images were acquired. The whole brain network was analyzed using graph theory analysis. DC was compared among groups using the two-sample t-test. The DC values of disrupted brain regions were correlated with the FOG Questionnaire (FOGQ) scores. Receiver operating characteristic curve analysis was performed. We found significant differences in DC among groups. Compared with HCs, PD FOG+ patients showed decreased DC in the middle frontal gyrus (MFG), superior temporal gyrus (STG), parahippocampal gyrus (PhG), inferior temporal gyrus (ITG), and middle temporal gyrus (MTG). Compared with HC, PD FOG- presented with decreased DC in the MFG, STG, PhG, and ITG. Compared with PD FOG-, PD FOG+ showed decreased DC in the MFG and ITG. A negative correlation existed between the DC of ITG and FOGQ scores; the DC in ITG could distinguish PD FOG+ from PD FOG- and HC. The calculated AUCs were 81.3, 89.5, and 77.7% for PD FOG+ vs. HC, PD FOG- vs. HC, and PD FOG+ vs. PD FOG-, respectively. In conclusion, decreased DC of ITG in PD FOG+ patients compared to PD FOG- patients and HCs may be a unique feature for PD FOG+ and can likely distinguish PD FOG+ from PD FOG- and HC groups.

Integrating Structural and Functional Interhemispheric Brain Connectivity of Gait Freezing in Parkinson's Disease.

Freezing of gait (FOG) has devastating consequences for patients with Parkinson's disease (PD), but the underlying pathophysiological mechanism is unclear. This was investigated in the present study by integrated structural and functional connectivity analyses of PD patients with or without FOG (PD FOG+ and PD FOG-, respectively) and healthy control (HC) subjects. We performed resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging of 24 PD FOG+ patients, 37 PD FOG- patients, and 24 HCs. Tract-based spatial statistics was applied to identify white matter (WM) abnormalities across the whole brain. Fractional anisotropy (FA) and mean diffusivity (MD) of abnormal WM areas were compared among groups, and correlations between these parameters and clinical severity as determined by FOG Questionnaire (FOGQ) score were analyzed. Voxel-mirrored homotopic connectivity (VMHC) was calculated to identify brain regions with abnormal interhemispheric connectivity. Structural and functional measures were integrated by calculating correlations between VMHC and FOGQ score and between FA, MD, and VMHC. The results showed that PD FOG+ and PD FOG- patients had decreased FA in the corpus callosum (CC), cingulum (hippocampus), and superior longitudinal fasciculus and increased MD in the CC, internal capsule, corona radiata, superior longitudinal fasciculus, and thalamus. PD FOG+ patients had more WM abnormalities than PD FOG- patients. FA and MD differed significantly among the splenium, body, and genu of the CC in all three groups (P < 0.05). The decreased FA in the CC was positively correlated with FOGQ score. PD FOG+ patients showed decreased VMHC in the post-central gyrus (PCG), pre-central gyrus, and parietal inferior margin. In PD FOG+ patients, VMHC in the PCG was negatively correlated with FOGQ score but positively correlated with FA in CC. Thus, FOG is associated with impaired interhemispheric brain connectivity measured by FA, MD, and VMHC, which are related to clinical FOG severity. These results demonstrate that integrating structural and functional MRI data can provide new insight into the pathophysiological mechanism of FOG in PD.

Aberrant Amplitude of Low-Frequency Fluctuations in Different Frequency Bands in Patients With Parkinson's Disease.

Previous studies reported abnormal spontaneous neural activity in Parkinson's disease (PD) patients using resting-state functional magnetic resonance imaging (R-fMRI). However, the frequency-dependent neural activity in PD is largely unknown. Here, 35 PD patients and 35 age- and education-matched healthy controls (HCs) underwent R-fMRI scanning to investigate abnormal spontaneous neural activity of PD using the amplitude of low-frequency fluctuation (ALFF) approach within the conventional band (typical band: 0.01-0.08 Hz) and specific frequency bands (slow-5: 0.010-0.027 Hz and slow-4: 0.027-0.073 Hz). Compared with HCs, PD patients exhibited increased ALFF in the parieto-temporo-occipital regions, such as the bilateral inferior temporal gyrus/fusiform gyrus (ITG/FG) and left angular gyrus/posterior middle temporal gyrus (AG/pMTG), and displayed decreased ALFF in the left cerebellum, right precuneus, and left postcentral gyrus/supramarginal gyrus (PostC/SMG) in the typical band. PD patients showed greater increased ALFF in the left caudate/putamen, left anterior cingulate cortex/medial superior frontal gyrus (ACC/mSFG), left middle cingulate cortex (MCC), right ITG, and left hippocampus, along with greater decreased ALFF in the left pallidum in the slow-5 band, whereas greater increased ALFF in the left ITG/FG/hippocampus accompanied by greater decreased ALFF in the precentral gyrus/PostC was found in the slow-4 band (uncorrected). Additionally, the left caudate/putamen was positively correlated with levodopa equivalent daily dose (LEDD), Hoehn and Yahr (HY) stage, and disease duration. Our results suggest that PD is related to widespread abnormal brain activities and that the abnormalities of ALFF in PD are associated with specific frequency bands. Future studies should take frequency band effects into account when examining spontaneous neural activity in PD.

Exploring Cortical Thickness Alteration in Parkinson Disease Patients with Freezing of Gaits.

Background: Freezing of gait (FoG) is a disabling gait disorder that commonly occurs in advanced stages of Parkinson's disease (PD). The neuroanatomical mechanisms underlying FoG in PD are still unclear. The present study aims to explore alterations of structural gray matter (GM) in PD patients with FoG. Method: Twenty-four PD patients with FoG (FoG+), 37 PD patients without FoG (FoG-) and 24 healthy controls (HC) were included. All subjects underwent a standardized MRI protocol. The cortical thickness (CTh), segmentation volume without ventricles (BrainSegVolNotVent) and estimated total intracranial volume (eTIV) were analysed using the FreeSurfer pipeline. Results: CTh differences were found in the right middle temporal gyrus (rMTG) generally. Compared to that in HCs, the CTh of the rMTG in both the FoG+ and FoG- groups was smaller, while no significant difference between the FoG+ and FoG- groups. Correlation analyses demonstrated a negative correlation between the CTh of the rMTG and the UPDRS part II score in PD subjects, and a borderline significant correlation between the score of Freezing of Gait Questionnaire (FoGQ) and rMTG CTh. Additionally, receiver operating characteristic curve (ROC) analysis revealed a cut-off point of CTh =3.08 mm in the rMTG that could be used to differentiate PD patients and HCs (AUC =0.79, P <0.01). There were no differences in the BrainSegVolNotVent or eTIV among the 3 groups. Conclusions: Our findings currently suggest no significant difference between FoG+ and FoG- patients in terms of structural gray matter changes. However, decreased CTh in the rMTG related to semantic control may be used as a biomarker to differentiate PD patients and HCs.

Impaired Topographical Organization of Functional Brain Networks in Parkinson's Disease Patients With Freezing of Gait.

Objective: This study aimed to explore alterations in the topological properties of the functional brain network in primary Parkinson's disease (PD) patients with freezing of gait (PD-FOG). Methods: Resting-state functional magnetic resonance imaging (Rs-fMRI) data were obtained in 23 PD-FOG patients, 33 PD patients without FOG (PD-nFOG), and 24 healthy control (HC) participants. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 90 brain regions, and topological properties were analyzed by using graph theory approaches. The network-based statistics (NBS) method was used to determine the suprathreshold connected edges (P < 0.05; threshold T = 2.725), and statistical significance was estimated by using the non-parametric permutation method (5,000 permutations). Statistically significant topological properties were further evaluated for their relationship with clinical neurological scales. Results: The topological properties of the functional brain network in PD-FOG and PD-nFOG showed no abnormalities at the global level. However, compared with HCs, PD-FOG patients showed decreased nodal local efficiency in several brain regions, including the bilateral striatum, frontoparietal areas, visual cortex, and bilateral superior temporal gyrus, increased nodal local efficiency in the left gyrus rectus. When compared with PD-nFOG patients and HCs, PD-FOG showed increased betweenness centrality in the left hippocampus. Moreover, compared to HCs, both PD-FOG and PD-nFOG patients displayed reduced network connections by using the NBS method, mainly involving the sensorimotor cortex (SM), visual network (VN), default mode network (DMN), auditory network (AN), dorsal attention network (DAN), subcortical regions, and limbic network (LIM). The local node efficiency of the right temporal pole: superior temporal gyrus in PD-FOG patients was positively correlated with the Freezing of Gait Questionnaire (FOGQ) scores. Conclusions: This study demonstrates the disrupted regional topological organization in PD-FOG patients, especially associated with damage to the subcortical regions and multiple cortical regions. Our results provide insights into the dysfunctional mechanisms of the relevant networks and indicate potential neuroimaging biomarkers of PD-FOG.

Aberrant Advanced Cognitive and Attention-Related Brain Networks in Parkinson's Disease with Freezing of Gait.

Background: Freezing of gait (FOG) is a disabling gait disorder influencing patients with Parkinson's disease (PD). Accumulating evidence suggests that FOG is related to the functional alterations within brain networks. We investigated the changes in brain resting-state functional connectivity (FC) in patients with PD with FOG (FOG+) and without FOG (FOG-). Methods: Resting-state functional magnetic resonance imaging (RS-fMRI) data were collected from 55 PD patients (25 FOG+ and 30 FOG-) and 26 matched healthy controls (HC). Differences in intranetwork connectivity between FOG+, FOG-, and HC individuals were explored using independent component analysis (ICA). Results: Seven resting-state networks (RSNs) with abnormalities, including motor, executive, and cognitive-related networks, were found in PD patients compared to HC. Compared to FOG- patients, FOG+ patients had increased FC in advanced cognitive and attention-related networks. In addition, the FC values of the auditory network and default mode network were positively correlated with the Gait and Falls Questionnaire (GFQ) and Freezing of Gait Questionnaire (FOGQ) scores in FOG+ patients. Conclusions: Our findings suggest that the neural basis of PD is associated with impairments of multiple functional networks. Notably, alterations of advanced cognitive and attention-related networks rather than motor networks may be related to the mechanism of FOG.

Intermittent Theta-Burst Stimulation Over the Suprahyoid Muscles Motor Cortex Facilitates Increased Degree Centrality in Healthy Subjects.

Theta-burst stimulation (TBS), a variant of repetitive transcranial magnetic stimulation (rTMS), can potentially benefit the treatment of swallowing disorders. However, the after-effects of TBS on the swallowing motor cortex remain uncertain. The newly developed graph-based analysis of the centrality approach has been increasingly used to explore brain networks. The purpose of this study was to identify degree centrality (DC) alterations in the brain network after different TBS protocols were performed over the suprahyoid muscles motor cortex in healthy subjects. A total of 40 right-handed healthy subjects (mean age: 23.73 ± 2.57 years, range: 21-30, 20 females) were included in this study and randomly assigned to two groups, including the continuous TBS (cTBS) group and the intermittent TBS (iTBS) group. All of the subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning before and after TBS implementation. Compared to the baseline, cTBS resulted in increased DC values in the left inferior frontal gyrus (P < 0.01). In the iTBS group, decreased DC was observed in the left cerebellum and left medial frontal gyrus; However, increased DC was observed in several brain areas including the right superior temporal gyrus, right superior frontal gyrus, right postcentral gyri and left paracentral lobule (P < 0.01). These results indicated that cTBS mainly results in increasing DC in the ipsilateral. However, iTBS is capable of facilitating the excitability of the swallowing motor cortex and increasing the connectivity of multiple brain regions, including the bilateral sensorimotor network, and might have therapeutic potential in the treatment of swallowing disorders.

Alterations of Regional Homogeneity in Parkinson's Disease Patients With Freezing of Gait: A Resting-State fMRI Study.

OBJECTIVE: The purposes of this study are to investigate the regional homogeneity (ReHo) of spontaneous brain activities in Parkinson's disease (PD) patients with freeze of gait (FOG) and to investigate the neural correlation of movement function through resting-state functional magnetic resonance imaging (RS-fMRI). METHODS: A total of 35 normal controls (NC), 33 PD patients with FOG (FOG+), and 35 PD patients without FOG (FOG-) were enrolled. ReHo was applied to evaluate the regional synchronization of spontaneous brain activities. Analysis of covariance (ANCOVA) was performed on ReHo maps of the three groups, followed by post hoc two-sample t-tests between every two groups. Moreover, the ReHo signals of FOG+ and FOG- were extracted across the whole brain and correlated with movement scores (FOGQ, FOG questionnaire; GFQ, gait and falls questionnaire). RESULTS: Significant ReHo differences were observed in the left cerebrum. Compared to NC subjects, the ReHo of PD subjects was increased in the left angular gyrus (AG) and decreased in the left rolandic operculum/postcentral gyrus (Rol/PostC), left inferior opercular-frontal cortex, left middle occipital gyrus, and supramarginal gyrus (SMG). Compared to that of FOG-, the ReHo of FOG+ was increased in the left caudate and decreased in the left Rol/PostC. Within the significant regions, the ReHo of FOG+ was negatively correlated with FOGQ in the left SMG/PostC (r = -0.39, p < 0.05). Negative correlations were also observed between ReHo and GFQ/FOGQ (r = -0.36/-0.38, p < 0.05) in the left superior temporal gyrus (STG) of the whole brain analysis based on AAL templates. CONCLUSION: The ReHo analysis suggested that the regional signal synchronization of brain activities in FOG+ subjects was most active in the left caudate and most hypoactive in the left Rol/PostC. It also indicated that ReHo in the left caudate and left Rol/PostC was critical for discriminating the three groups. The correlation between ReHo and movement scores (GFQ/FOGQ) in the STG has the potential to differentiate FOG+ from FOG-. This study provided new insight into the understanding of PD with and without FOG.

Altered Global Synchronizations in Patients With Parkinson's Disease: A Resting-State fMRI Study.

Background: Abnormalities of cognitive and movement functions are widely reported in Parkinson's disease (PD). The mechanisms therein are complicated and assumed to a coordination of various brain regions. This study explored the alterations of global synchronizations of brain activities and investigated the neural correlations of cognitive and movement function in PD patients. Methods: Thirty-five age-matched patients with PD and 35 normal controls (NC) were enrolled in resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Degree centrality (DC) was calculated to measure the global synchronizations of brain activity for two groups. Neural correlations between DC and cognitive function Frontal Assessment Battery (FAB), as well as movement function Unified Parkinson's Disease Rating Scale (UPDRS-III), were examined across the whole brain within Anatomical Automatic Labeling (AAL) templates. Results: In the PD group, increased DC was observed in left fusiform gyrus extending to inferior temporal gyrus, left middle temporal gyrus (MTG) and angular gyrus, while it was decreased in right inferior opercular-frontal gyrus extending to superior temporal gyrus (STG). The DC in a significant region of the fusiform gyrus was positively correlated with UPDRS-III scores in PD (r = 0.41, p = 0.0145). Higher FAB scores were shown in NC than PD (p < 0.0001). Correlative analysis of PD between DC and FAB showed negative results (p < 0.05) in frontal cortex, whereas positive in insula and cerebellum. As for the correlations between DC and UPDRS-III, negative correlation (p < 0.05) was observed in bilateral inferior parietal lobule (IPL) and right cerebellum, whereas positive correlation (p < 0.05) in bilateral hippocampus and para-hippocampus gyrus (p < 0.01). Conclusion: The altered global synchronizations revealed altered cognitive and movement functions in PD. The findings suggested that the global functional connectivity in fusiform gyrus, cerebellum and hippocampus gyrus are critical regions in the identification of cognitive and movement functions in PD. This study provides new insights on the interactions among global coordination of brain activity, cognitive and movement functions in PD.

Diffusion Tensor Magnetic Resonance Imaging in Chronic Spinal Cord Compression.

Chronic spinal cord compression is the most common cause of spinal cord impairment in patients with nontraumatic spinal cord damage. Conventional magnetic resonance imaging (MRI) plays an important role in both confirming the diagnosis and evaluating the degree of compression. However, the anatomical detail provided by conventional MRI is not sufficient to accurately estimate neuronal damage and/or assess the possibility of neuronal recovery in chronic spinal cord compression patients. In contrast, diffusion tensor imaging (DTI) can provide quantitative results according to the detection of water molecule diffusion in tissues. In the present study, we develop a methodological framework to illustrate the application of DTI in chronic spinal cord compression disease. DTI fractional anisotropy (FA), apparent diffusion coefficients (ADCs), and eigenvector values are useful for visualizing microstructural pathological changes in the spinal cord. Decreased FA and increases in ADCs and eigenvector values were observed in chronic spinal cord compression patients compared to healthy controls. DTI could help surgeons understand spinal cord injury severity and provide important information regarding prognosis and neural functional recovery. In conclusion, this protocol provides a sensitive, detailed, and noninvasive tool to evaluate spinal cord compression.

Intermittent Theta-Burst Stimulation Reverses the After-Effects of Contralateral Virtual Lesion on the Suprahyoid Muscle Cortex: Evidence From Dynamic Functional Connectivity Analysis.

Contralateral intermittent theta burst stimulation (iTBS) can potentially improve swallowing disorders with unilateral lesion of the swallowing cortex. However, the after-effects of iTBS on brain excitability remain largely unknown. Here, we investigated the alterations of temporal dynamics of inter-regional connectivity induced by iTBS following continuous TBS (cTBS) in the contralateral suprahyoid muscle cortex. A total of 20 right-handed healthy subjects underwent cTBS over the left suprahyoid muscle motor cortex and then immediately afterward, iTBS was applied to the contralateral homologous area. All of the subjects underwent resting-state functional magnetic resonance imaging (Rs-fMRI) pre- and post-TBS implemented on a different day. We compared the static and dynamic functional connectivity (FC) between the post-TBS and the baseline. The whole-cortical time series and a sliding-window correlation approach were used to quantify the dynamic characteristics of FC. Compared with the baseline, for static FC measurement, increased FC was found in the precuneus (BA 19), left fusiform gyrus (BA 37), and right pre/post-central gyrus (BA 4/3), and decreased FC was observed in the posterior cingulate gyrus (PCC) (BA 29) and left inferior parietal lobule (BA 39). However, in the dynamic FC analysis, post-TBS showed reduced FC in the left angular and PCC in the early windows, and in the following windows, increased FC in multiple cortical areas including bilateral pre- and postcentral gyri and paracentral lobule and non-sensorimotor areas including the prefrontal, temporal and occipital gyrus, and brain stem. Our results indicate that iTBS reverses the aftereffects induced by cTBS on the contralateral suprahyoid muscle cortex. Dynamic FC analysis displayed a different pattern of alteration compared with the static FC approach in brain excitability induced by TBS. Our results provide novel evidence for us in understanding the topographical and temporal aftereffects linked to brain excitability induced by different TBS protocols and might be valuable information for their application in the rehabilitation of deglutition.