Luqing Wei

Specific frequency band of amplitude low-frequency fluctuation predicts Parkinson's disease

Resting-state functional magnetic resonance imaging (RS-fMRI) has been considered for development as a biomarker and analytical tool for evaluation of Parkinsons disease (PD). Here we utilized analysis of the amplitude low-frequency fluctuations (ALFF) to determine changes in intrinsic neural oscillations in 72 patients with PD. Two different frequency bands (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz) were analyzed. In the slow-5 band, PD patients compared with controls had increased ALFF values mainly in the caudate and several temporal regions, as well as decreased ALFF values in the cerebellum and the parieto-temporo-occipital cortex. Additionally, in the slow-4 band, PD patients relative to controls exhibited reduced ALFF value in the thalamus, cerebellum, and several occipital regions. Together, our data demonstrate that PD patients have widespread abnormal intrinsic neural oscillations in the corticostriatal network in line with the pathophysiology of PD, and further suggest that the abnormalities are dependent on specific frequency bands. Thus, frequency domain analyses of resting state BOLD signals may provide a useful means to study the pathophysiology of PD and the physiology of the brains dopaminergic pathways.

Akinetic-rigid and tremor-dominant Parkinson's disease patients show different patterns of intrinsic brain activity

BACKGROUND Parkinsons disease (PD) is a surprisingly heterogeneous neurodegenerative disorder. It is well established that different subtypes of PD present with different clinical courses and prognoses. However, the neural mechanism underlying these disparate presentations is uncertain. METHODS Here we used resting-state fMRI (rs-fMRI) and the regional homogeneity (ReHo) method to determine neural activity patterns in the two main clinical subgroups of PD (akinetic-rigid and tremor-dominant). RESULTS Compared with healthy controls, akinetic-rigid (AR) subjects had increased ReHo mainly in right amygdala, left putamen, bilateral angular gyrus, bilateral medial prefrontal cortex (MPFC), and decreased ReHo in left post cingulate gyrus/precuneus (PCC/PCu) and bilateral thalamus. In contrast, tremor-dominant (TD) patients showed higher ReHo mostly in bilateral angular gyrus, left PCC, cerebellum_crus1, and cerebellum_6, while ReHo was decreased in right putamen, primary sensory cortex (S1), vermis_3, and cerebellum_4_5. These results indicate that AR and TD subgroups both represent altered spontaneous neural activity in default-mode regions and striatum, and AR subjects exhibit more changed neural activity in the mesolimbic cortex (amygdala) but TD in the cerebellar regions. Of note, direct comparison of the two subgroups revealed a distinct ReHo pattern primarily located in the striatal-thalamo-cortical (STC) and cerebello-thalamo-cortical (CTC) loops. CONCLUSION Overall, our findings highlight the involvement of default mode network (DMN) and STC circuit both in AR and TD subtypes, but also underscore the importance of integrating mesolimbic-striatal and CTC loops in understanding neural systems of akinesia and rigidity, as well as resting tremor in PD. This study provides improved understanding of the pathophysiological models of different subtypes of PD.

Gray matter volume abnormalities in type 2 diabetes mellitus with and without mild cognitive impairment.

This study sought to evaluate the potential brain gray matter (GM) volume changes that occur with the transition from normal cognition to mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM) using voxel-based morphometry (VBM). VBM analyses of brain GM based on magnetic resonance imaging (MRI) data were performed on 28 T2DM patients with MCI, 25 T2DM patients without MCI, 28 MCI patients and 29 healthy controls (HC). Compared with the HC, the T2DM patients both with and without MCI showed significantly decreased total GM volume. Furthermore, the VBM results indicated that the T2DM patients without MCI exhibited extensively decreased GM volume compared with the HC in certain brain regions, including the superior and middle temporal gyrus (MTG), the superior and medial frontal gyrus and the middle occipital gyrus. In addition to more extensive GM atrophy in the aforementioned brain regions, the medial temporal lobe also exhibited GM loss in the T2DM patients with MCI. Furthermore, relative to the patients without MCI, only the left MTG exhibited a lower GM volume in the T2DM patients with MCI, which was positively correlated with the total MoCA score (r=0.699, P<0.01). Finally, relative to MCI, the left MTG atrophy was also found in the T2DM patients with MCI. Our findings suggest that MTG atrophy was associated with an increased risk for MCI in T2DM patients. The brain structural changes in many brain regions may underlie the transition from normal cognition to MCI in T2DM patients.

Reduced Topological Efficiency in Cortical-Basal Ganglia Motor Network of Parkinson's Disease: A Resting State fMRI Study

Parkinsons disease (PD) is mainly characterized by dopamine depletion of the cortico-basal ganglia (CBG) motor circuit. Given that dopamine dysfunction could affect functional brain network efficiency, the present study utilized resting-state fMRI (rs-fMRI) and graph theoretical approach to investigate the topological efficiency changes of the CBG motor network in patients with PD during a relatively hypodopaminergic state (12 hours after a last dose of dopamimetic treatment). We found that PD compared with controls had remarkable decreased efficiency in the CBG motor network, with the most pronounced changes observed in rostral supplementary motor area (pre-SMA), caudal SMA (SMA-proper), primary motor cortex (M1), primary somatosensory cortex (S1), thalamus (THA), globus pallidus (GP), and putamen (PUT). Furthermore, reduced efficiency in pre-SMA, M1, THA and GP was significantly correlated with Unified Parkinsons Disease Rating Scale (UPDRS) motor scores in PD patients. Together, our results demonstrate that individuals with PD appear to be less effective at information transfer within the CBG motor pathway, which provides a novel perspective on neurobiological explanation for the motor symptoms in patients. These findings are in line with the pathophysiology of PD, suggesting that network efficiency metrics may be used to identify and track the pathology of PD.

Morphologic changes in the anterior and posterior subregions of V1 and V2 and the V5/MT+ in patients with primary open-angle glaucoma.

The aim of this study was to investigate possible morphologic changes of the visual cortex in primary open-angle glaucoma (POAG) with varying severity. Twenty normal controls (NC), 19 mild (MP) and 17 severe (SP) POAG patients were recruited and scanned using magnetic resonance imaging. Multi-parameter morphologic analyses with regions of interest (V5/MT+, anterior and posterior subregions of V1 and V2) were used to assess the cortical changes among the three groups. Compared with the NC group, decreased cortical thickness was detected in the V5/MT+ area in the MP group and in all of the investigated visual areas except the posterior subregion of V1 in the SP group. Unexpectedly, cortical thinning of the posterior subregion of V2 was detected in the SP group compared with the NC and MP groups. For the other morphologic parameters, only gray matter volume in the posterior subregion of V2 and mean curvature in the V5/MT+ were significantly changed in the SP group. In addition, the clinical measurements were positively correlated with the cortical thickness of the V5/MT+ and the posterior subregion of V2. In conclusion, the V5/MT+ area is involved in early disruption of POAG and the cortical degeneration may be progressive and heterogeneous in different visual cortices. Early neuroprotective therapies on the retina and central visual system may help to preserve vision in patients with POAG.

Decreased interhemispheric functional connectivity in subtypes of Parkinson's disease.

Abstract Parkinson’s disease (PD) can be classified into tremor-dominant (TD) subtype and akinetic-rigid (AR) subtype, which exhibit different clinical courses and prognoses. However, the neural mechanisms underlying different subtypes of PD are not well understood. Using voxel-mirrored homotopic connectivity (VMHC), we examined the homotopic resting-state functional connectivity patterns in akinetic-rigid PD (AR-PD) and tremor-dominant PD (TD-PD) to study the neural basis for these disparate manifestations of PD. Twenty-one TD-PD patients, 29 AR-PD patients and 26 normal control subjects participated in this study. Resting-state fMRI data were analyzed using VMHC. Correlations between VMHC values and each clinical characteristic were also calculated. Compared with normal control subjects and subjects with AR-PD, subjects with TD-PD exhibited significantly lower VMHC values in the posterior lobe of the cerebellum. Moreover, tremor scores and VMHC values for the cerebellum were found to be significantly negatively correlated in TD-PD patients. By contrast, subjects with AR-PD exhibited lower VMHC values in the precentral gyrus compared with normal control subjects. These findings suggest that functional coordination between homotopic brain regions is impaired in AR-PD and TD-PD patients. This study provides evidence of both cerebellum-related connectivity deficits in TD-PD. The finding that VMHC values and tremor scores were significantly correlated suggests that VMHC measurements may be of potential clinical relevance in TD-PD.

Amplitude of Low-frequency Oscillations in Parkinson's Disease: A 2-year Longitudinal Resting-state Functional Magnetic Resonance Imaging Study

Background: Neuroimaging studies have found that functional changes exist in patients with Parkinsons disease (PD). However, the majority of functional magnetic resonance imaging (fMRI) studies in patients with PD are task-related and cross-sectional. This study investigated the functional changes observed in patients with PD, at both baseline and after 2 years, using resting-state fMRI. It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics. Methods: Seventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI. In addition, 20 age- and sex-matched, healthy controls were examined using resting-state fMRI. The fractional amplitude of low-frequency fluctuation (fALFF) approach was used to analyze the fMRI data. Nonlinear registration was used to model within-subject changes over the scanning interval, as well as changes between the patients with PD and the healthy controls. A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences. Results: Compared to the control subjects, the patients with PD showed increased fALFF values in the left inferior temporal gyrus, right inferior parietal lobule (IPL) and right middle frontal gyrus. Compared to the baseline in the 2 years follow-up, the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum, right thalamus, right striatum, left superior parietal lobule, left IPL, left precentral gyrus, and left postcentral gyrus (P < 0.01, after correction with AlphaSim). In addition, the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale (UPDRS) motor scores (r = 0.51, P < 0.05, uncorrected) and the change in the UPDRS motor score (r = 0.61, P < 0.05, uncorrected). Conclusions: The baseline and longitudinal changes of the fALFF values in our study suggest that dysfunction in the brain may affect the regions related to cortico-striato-pallido-thalamic loops and cerebello-thalamo-cortical loops as the disease progresses and that alterations to the spontaneous neural activity of the cerebellum may also play an important role in the diseases progression in patients with PD.

Frequency-dependent changes in the amplitude of low-frequency fluctuations in subcortical ischemic vascular disease (SIVD): a resting-state fMRI study.

Resting-state functional magnetic resonance imaging (RS-fMRI) allowed researchers to detect intrinsic brain activity during rest and has been considered an analytical tool for evaluation of dementia. Previously, subcortical ischemic vascular disease (SIVD) has been found decreased amplitude low-frequency fluctuations (ALFF) in a widely frequency range (0.01-0.08Hz) in the bilateral precuneus and increased ALFF values in the bilateral anterior cingulate cortex (ACC), left insula and hippocampus, which showed significant correlations with the cognitive performance. In this study we analyzed the ALFF of 30 patients with SIVD in two different frequency bands (slow-5: 0.01-0.027Hz; slow-4: 0.027-0.073Hz). In the slow-5 band, SIVD patients compared with controls exhibited significant higher ALFF in the bilateral anterior cingulate cortex, right putamen and right supplementary motor area, while lower ALFF in the right precuneus and right angular gyrus. A close correlation was found between the ALFF value of the right angular gyrus and ADL scores. In the slow-4 band, SIVD patients only exhibited increased ALFF in the bilateral anterior cingulate cortex, right putamen, left fusiform gyrus, and no correlation with cognitive scores was found. Our data demonstrate that SIVD patients have widespread abnormal intrinsic neural oscillations, which are dependent on specific frequency bands. ALFF of right angular gyrus at slow-5 band is more specific for SIVD and may be a useful tool to help SIVD diagnosis.

The thalamus in cirrhotic patients with and without hepatic encephalopathy: A volumetric MRI study

BACKGROUND & AIMS The thalamus is a major relay and filter station in the central neural system. Some previous studies have suggested that the thalamus maybe implicated in the pathogenesis of hepatic encephalopathy. The aim of our study was to investigate changing thalamic volumes in cirrhotic patients with and without hepatic encephalopathy. METHODS Neuropsychological tests and structural MR scanning were performed on 24 cirrhotic patients, 23 cirrhotic patients with minimal hepatic encephalopathy, 24 cirrhotic patients during their first episode of overt hepatic encephalopathy, and 33 healthy controls. Voxel-based morphometry analysis was performed to detect gray matter morphological changes. The thalamus and whole brain volume were extrapolated. A receiver operating characteristic curve analysis of thalamic volumes was used to discriminate patients with minimal hepatic encephalopathy from those with hepatic cirrhosis. RESULTS Thalamic volume increased in a stepwise manner in patients with progressively worse stages of hepatic encephalopathy compared to healthy subjects. Additionally, a comparison of gray matter morphometry between patients with Child-Pugh grades A, B, or C and controls revealed a progression in thalamic volumes in parallel with the degree of liver failure. Moreover, thalamic volume was significantly correlated with the number connection test A time and digit-symbol test score in cirrhotic patients with minimal hepatic encephalopathy (r=0.659, P=0.001; r=-0.577, P=0.004; respectively). The area under the receiver operating characteristic curve was 0.827 (P=0.001). CONCLUSIONS A significantly increased thalamic volume may be provide an objective imaging measure for predicting seizures due to minimal hepatic encephalopathy in cirrhotic patients.

Memory Dysfunction in Type 2 Diabetes Mellitus Correlates with Reduced Hippocampal CA1 and Subiculum Volumes

Background:Little attention has been paid to the role of subcortical deep gray matter (SDGM) structures in type 2 diabetes mellitus (T2DM)-induced cognitive impairment, especially hippocampal subfields. Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging (MRI) and to test their associations with cognitive performance in T2DM. Methods:A total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age, sex and education level was enrolled in this study. We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry. We used Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores as measures of cognitive performance. The association of glycosylated hemoglobin (HbA1c) with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM. Results:Bilaterally, the hippocampal volumes were smaller in T2DM patients, mainly in the CA1 and subiculum subfields. Partial correlation analysis showed that the MoCA scores, particularly those regarding delayed memory, were significantly positively correlated with reduced hippocampal CA1 and subiculum volumes in T2DM patients. Additionally, higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients. Conclusions:These data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction, suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.