Precuneus Dysfunction in Parkinson’s Disease With Mild Cognitive Impairment

Background: Mild cognitive impairment (MCI) frequently occurs in Parkinson’s disease (PD). Neurovascular changes interact with neurodegenerative processes in PD. However, the deficits of cerebral blood flow (CBF) perfusion and the associated functional connectivity (FC) in PD patients with MCI (PD-MCI) remain unclear.Purpose: This study aimed to explore the specific neurovascular perfusion alterations in PD-MCI compared to PD with normal cognition (PD-NC) and healthy controls (HCs), and to further examine the resultant whole brain FC changes in the abnormal perfusion regions.Methods: Relative CBF (rCBF) was calculated using arterial spin labeling (ASL) in 54 patients with PD (27 patients with PD-NC and 27 patients with PD-MCI) and 25 HCs matched for age and gender ratio, who also underwent the structural MRI, resting-state functional MRI (rs-fMRI) and neuropsychological examinations. The gray matter (GM) changes in PD patients were analyzed using voxel-based morphometry (VBM). The alterations in rCBF perfusion and FC among groups were then analyzed respectively. Additionally, correlations between these alterations and neuropsychological performances were further examined.Results: Compared to HC, left caudate atrophy was detected in patients with PD. In comparison to both PD-NC and HC, patients with PD-MCI specifically exhibited hypoperfusion in the parietal memory network (PMN) in the precuneus (PCu) and decreased PCu-FC in the right striatum. Moreover, PCu perfusion and PCu-FC strengths in the right striatum were positively associated with memory performance in PD-MCI.Conclusions: These findings suggest that the posterior PMN dysfunction underlies memory deficits in PD-MCI

Identifying the Alteration Patterns of Brain Functional Connectivity in Progressive Mild Cognitive Impairment Patients: A Longitudinal Whole-Brain Voxel-Wise Degree Analysis

Patients with mild cognitive impairment (MCI) are at high risk for developing Alzheimer’s disease (AD), while some of them may remain stable over decades. The underlying mechanism is still not fully understood. In this study, we aimed to explore the connectivity differences between progressive MCI (PMCI) and stable MCI (SMCI) individuals on a whole-brain scale and on a voxel-wise basis, and we also aimed to reveal the differential dynamic alternation patterns between these two disease subtypes. The resting-state functional magnetic resonance images of PMCI and SMCI patients at baseline and year-one were obtained from the Alzheimer’s Disease Neuroimaging Initiative dataset, and the progression was determined based on a three-year follow-up. A whole-brain voxel-wise degree map that was calculated based on graph-theory was constructed for each subject, and then the cross-sectional and longitudinal analyses on the degree maps were performed between PMCI and SMCI patients. In longitudinal analyses, compared with SMCI group, PMCI group showed decreased long-range degree in the left middle occipital/supramarginal gyrus, while the short-range degree was increased in the left supplementary motor area and middle frontal gyrus and decreased in the right middle temporal pole. A significant longitudinal alteration of decreased short-range degree in the right middle occipital was found in PMCI group. Taken together with previous evidence, our current findings may suggest that PMCI, compared with SMCI, might be a severe presentation of disease along the AD continuum, and the rapidly reduced degree in the right middle occipital gyrus may have indicative value for the disease progression. Moreover, the cross-sectional comparison results and corresponding receiver-operator characteristic-curves analyses may indicate that the baseline degree difference is not a good predictor of disease progression in MCI patients. Overall, these findings may provide objective evidence and an indicator to characterize the progression-related brain connectivity changes in MCI patients

Altered Functional Connectivity of the Basal Nucleus of Meynert in Mild Cognitive Impairment: A Resting-State fMRI Study

Background: Cholinergic dysfunction plays an important role in mild cognitive impairment (MCI). The basal nucleus of Meynert (BNM) provides the main source of cortical cholinergic innervation. Previous studies have characterized structural changes of the cholinergic basal forebrain in individuals at risk of developing Alzheimer’s disease (AD). However, whether and how functional connectivity of the BNM (BNM-FC) is altered in MCI remains unknown.Objective: The aim of this study was to identify alterations in BNM-FC in individuals with MCI as compared to healthy controls (HCs), and to examine the relationship between these alterations with neuropsychological measures in individuals with MCI.Method: One-hundred-and-one MCI patients and 103 HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI). Imaging data were processed with SPM8 and CONN software. BNM-FC was examined via correlation in low frequency fMRI signal fluctuations between the BNM and all other brain voxels. Group differences were examined with a covariance analysis with age, gender, education level, mean framewise displacement (FD) and global correlation (GCOR) as nuisance covariates. Pearson’s correlation was conducted to evaluate the relationship between the BNM-FC and clinical assessments.Result: Compared with HCs, individuals with MCI showed significantly decreased BNM-FC in the left insula extending into claustrum (insula/claustrum). Furthermore, greater decrease in BNM-FC with insula/claustrum was associated with more severe impairment in immediate recall during Auditory Verbal Learning Test (AVLT) in MCI patients.Conclusion: MCI is associated with changes in BNM-FC to the insula/claustrum in relation to cognitive impairments. These new findings may advance research of the cholinergic bases of cognitive dysfunction during healthy aging and in individuals at risk of developing AD

Common and segregated neural substrates for automatic conceptual and affective priming as revealed by event-related functional magnetic resonance imaging

The brain activity associated with automatic semantic priming has been extensively studied. Thus far there has been no prior study that directly contrasts the neural mechanisms of semantic and affective priming. The present study employed event-related fMRI to examine the common and distinct neural bases underlying conceptual and affective priming with a lexical decision task. A special type of emotional word. a dual-meaning word containing both conceptual meaning and affective meaning, was adopted as target. Short stimulus onset asynchrony (SOA) (50 ms) was used to emphasize automatic processing. Fifteen participants were scanned in the present study. We found that the left middle/superior temporal gyrus was the brain region involved in both automatic conceptual and affective priming effects, suggesting general lexical-semantic processing that share in the two types of priming. The left inferior frontal gyrus and right superior temporal gyrus were found to be the conceptual-specific areas in automatic priming effect, consistent with the role of these areas in more extensive within-category semantic processes. The results also revealed that the left fusiform gyrus and left insula were the affective-specific regions in automatic priming effect, demonstrating the involvement of the left fusiform gyrus in automatic affective priming effect, and clarifying the role of the insula in emotional processing rather than conceptual processing. Despite comparable behavioral effects of automatic conceptual priming and affective priming, the present study revealed a neural dissociation of the two types of priming, as well as the shared neural bases

Disruption of cortical integration during midazolam-induced light sedation: Effects of Midazolam-Induced Sedation on RSNs

This work examines the effect of midazolam‐induced light sedation on intrinsic functional connectivity of human brain, using a randomized, double‐blind, placebo‐controlled, cross‐over, within‐subject design. Fourteen healthy young subjects were enrolled and midazolam (0.03 mg/kg of the participant's body mass, to a maximum of 2.5 mg) or saline were administrated with an interval of one week. Resting‐state fMRI was conducted before and after administration for each subject. We focus on two types of networks: sensory related lower‐level functional networks and higher‐order functions related ones. Independent component analysis (ICA) was used to identify these resting‐state functional networks. We hypothesize that the sensory (visual, auditory, and sensorimotor) related networks will be intact under midazolam‐induced light sedation while the higher‐order (default mode, executive control, salience networks, etc.) networks will be functionally disconnected. It was found that the functional integrity of the lower‐level networks was maintained, while that of the higher‐level networks was significantly disrupted by light sedation. The within‐network connectivity of the two types of networks was differently affected in terms of direction and extent. These findings provide direct evidence that higher‐order cognitive functions including memory, attention, executive function, and language were impaired prior to lower‐level sensory responses during sedation. Our result also lends support to the information integration model of consciousness. Hum Brain Mapp 36:4247–4261, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc