Lenka Krajčovičová

The default mode network integrity in patients with Parkinson’s disease is levodopa equivalent dose-dependent

Disturbances in the default mode network (DMN) have been described in many neurological and psychiatric disorders including Parkinson’s disease (PD). The DMN is characterized by basal activity that increases during rest or passive visual fixation and decreases (“deactivates”) during cognitive tasks. The network is believed to be involved in cognitive processes. We examined the DMN in PD patients on dopaminergic medication with normal cognitive performance compared to age- and gender-matched healthy controls (HC) using fMRI and three methodological procedures: independent component analysis of resting-state data, analysis of deactivation during a complex visual scene-encoding task, and seed-based functional connectivity analysis. In the PD group, we also studied the effect of dopaminergic medication on the DMN integrity. We did not find any difference between the PD and HC groups in the DMN, but using the daily levodopa equivalent dose as a covariate, we observed an enhanced functional connectivity of the DMN in the posterior cingulate cortex and decreased activation in the left parahippocampal gyrus during the cognitive task. We conclude that dopaminergic therapy has a specific effect on both the DMN integrity and task-related brain activations in cognitively unimpaired PD patients, and these effects seem to be dose-dependent.

Default Mode Network and Extrastriate Visual Resting State Network in Patients with Parkinson’s Disease Dementia

Aims: Using fMRI, we evaluated the default mode network (DMN) and the extrastriate visual resting state network (ESV-RSN) in 14 patients with Parkinson’s disease dementia (PDD) as compared with 18 patients with Parkinson’s disease (PD) without dementia and 18 healthy controls (HC). Methods: We analyzed the seed-based functional connectivity of both resting state data and deactivations during a visual complex scene-encoding task. Results: Using the posterior cingulate cortex/precuneus as a seed for the DMN analysis, we observed significant decreases of connectivity in the right inferior frontal gyrus in PDD as compared to PD and HC. Using the caudate nucleus as a seed for the ESV-RSN analysis, we found significant decreases of connectivity in the left and right inferior occipital gyrus in PDD as compared to HC. Conclusion: Differences in functional connectivity patterns between PDD and PD/HC were observed in areas known to be engaged in stimulus-driven reorienting of attention and in visual processing.

Disruption of resting functional connectivity in Alzheimer's patients and at-risk subjects.

The resting brain exhibits continuous intrinsic activity, which is correlated between groups of regions forming resting state networks. Evaluating resting connectivity is a popular approach for studying brain diseases. Several hundred studies are now available that address integrity of resting connectivity in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), as well as preclinical at-risk subjects. Most studies focus on the default mode network, a system of specific brain areas showing strong connected resting activity that attenuates during goal-directed behavior. The extent of intrinsic brain activity tends to be strongly correlated with cognitive processes and is specifically disrupted in AD and MCI patients and at-risk subjects, with changes seeming to evolve during the transition between the disease stages. In this study, we review the current findings in default mode network and other resting state network studies in AD and MCI patients and at-risk subjects as assessed by resting state functional magnetic resonance imaging.

Default mode network connectivity patterns associated with visual processing at different stages of Parkinson's disease.

BACKGROUND The default mode network (DMN) decreases its activity when switching from a resting state to a cognitive task condition, while activity of the network engaged in the given task increases. Visual processing is typically disturbed in Parkinsons disease dementia (PDD). OBJECTIVE Using functional MRI, we studied the DMN effective connectivity patterns in PDD as compared with cognitively normal patients with Parkinsons disease (PD) and healthy controls (HC) when switching from baseline to a visual cognitive task condition. METHODS In all, 14 PDD, 18 PD, and 18 age-matched healthy controls participated in this functional MRI study. We used a psychophysiological interaction analysis with the precuneus (PCu) as a seed. The threshold was set at p(FWE) <0.05. RESULTS The healthy controls showed greater PCu connectivity with the bilateral middle temporal/middle occipital gyri at baseline than during the task condition. The correlation direction changed from positive to negative. Both PD and PDD showed disturbed DMN connectivity with the brain regions that are involved in bottom-up visual processing. In PD, we also found impaired integration of the areas engaged in the ventral attentional network, which might reflect specific attentional deficits observed during the early course of PD. In mild PDD, we detected increased engagement of areas involved in the dorsal attentional network, which corresponds to increased top-down control in this patient group as compared to the healthy controls. CONCLUSION Our results show impaired dynamic interplay between large scale brain networks in PD that spread far beyond the motor system.

Disturbed Default Mode Network Connectivity Patterns in Alzheimer's Disease Associated with Visual Processing

Changes in connectivity of the posterior node of the default mode network (DMN) were studied when switching from baseline to a cognitive task using functional magnetic resonance imaging. In all, 15 patients with mild to moderate Alzheimers disease (AD) and 18 age-, gender-, and education-matched healthy controls (HC) participated in the study. Psychophysiological interactions analysis was used to assess the specific alterations in the DMN connectivity (deactivation-based) due to psychological effects from the complex visual scene encoding task. In HC, we observed task-induced connectivity decreases between the posterior cingulate and middle temporal and occipital visual cortices. These findings imply successful involvement of the ventral visual pathway during the visual processing in our HC cohort. In AD, involvement of the areas engaged in the ventral visual pathway was observed only in a small volume of the right middle temporal gyrus. Additional connectivity changes (decreases) in AD were present between the posterior cingulate and superior temporal gyrus when switching from baseline to task condition. These changes are probably related to both disturbed visual processing and the DMN connectivity in AD and reflect deficits and compensatory mechanisms within the large scale brain networks in this patient population. Studying the DMN connectivity using psychophysiological interactions analysis may provide a sensitive tool for exploring early changes in AD and their dynamics during the disease progression.

2.033 DEFAULT MODE NETWORK AND EXTRASTRIATE VISUAL RESTING STATE NETWORK IN PATIENTS WITH PARKINSON'S DISEASE DEMENTIA

Aims: Using fMRI, we evaluated the default mode network (DMN) and the extrastriate visual resting state network (ESV-RSN) in 14 patients with Parkinsons disease dementia (PDD) as compared with 18 patients with Parkinsons disease (PD) without dementia and 18 healthy controls (HC). Methods: We analyzed the seed-based functional connectivity of both resting state data and deactivations during a visual complex scene-encoding task. Results: Using the posterior cingulate cortex/precuneus as a seed for the DMN analysis, we observed significant decreases of connectivity in the right inferior frontal gyrus in PDD as compared to PD and HC. Using the caudate nucleus as a seed for the ESV-RSN analysis, we found significant decreases of connectivity in the left and right inferior occipital gyrus in PDD as compared to HC. Conclusion: Differences in functional connectivity patterns between PDD and PD/HC were observed in areas known to be engaged in stimulus-driven reorienting of attention and in visual processing. Copyright (C) 2012 S. Karger AG, Basel

Heart valve abnormalities in Parkinson's disease treated with dopamine agonists.

Heart valve abnormalities in Parkinsons disease treated with dopamine agonists, letter to the editor

Small effect size leads to reproducibility failure in resting-state fMRI studies

Thousands of papers using resting-state functional magnetic resonance imaging (RS-fMRI) have been published on brain disorders. Results in each paper may have survived correction for multiple comparison. However, since there have been no robust results from large scale meta-analysis, we do not know how many of published results are truly positives. The present meta-analytic work included 60 original studies, with 57 studies (4 datasets, 2266 participants) that used a between-group design and 3 studies (1 dataset, 107 participants) that employed a within-group design. To evaluate the effect size of brain disorders, a very large neuroimaging dataset ranging from neurological to psychiatric isorders together with healthy individuals have been analyzed. Parkinson’s disease off levodopa (PD-off) included 687 participants from 15 studies. PD on levodopa (PD-on) included 261 participants from 9 studies. Autism spectrum disorder (ASD) included 958 participants from 27 studies. The meta-analyses of a metric named amplitude of low frequency fluctuation (ALFF) showed that the effect size (Hedges’ g) was 0.19 - 0.39 for the 4 datasets using between-group design and 0.46 for the dataset using within-group design. The effect size of PD-off, PD-on and ASD were 0.23, 0.39, and 0.19, respectively. Using the meta-analysis results as the robust results, the between-group design results of each study showed high false negative rates (median 99%), high false discovery rates (median 86%), and low accuracy (median 1%), regardless of whether stringent or liberal multiple comparison correction was used. The findings were similar for 4 RS-fMRI metrics including ALFF, regional homogeneity, and degree centrality, as well as for another widely used RS-fMRI metric namely seed-based functional connectivity. These observations suggest that multiple comparison correction does not control for false discoveries across multiple studies when the effect sizes are relatively small. Meta-analysis on un-thresholded t-maps is critical for the recovery of ground truth. We recommend that to achieve high reproducibility through meta-analysis, the neuroimaging research field should share raw data or, at minimum, provide un-thresholded statistical images.

Changes in connectivity of the posterior default network node during visual processing in mild cognitive impairment: staged decline between normal aging and Alzheimer’s disease

Visual processing difficulties are often present in Alzheimer’s disease (AD), even in its pre-dementia phase (i.e. in mild cognitive impairment, MCI). The default mode network (DMN) modulates the brain connectivity depending on the specific cognitive demand, including visual processes. The aim of the present study was to analyze specific changes in connectivity of the posterior DMN node (i.e. the posterior cingulate cortex and precuneus, PCC/P) associated with visual processing in 17 MCI patients and 15 AD patients as compared to 18 healthy controls (HC) using functional magnetic resonance imaging. We used psychophysiological interaction (PPI) analysis to detect specific alterations in PCC connectivity associated with visual processing while controlling for brain atrophy. In the HC group, we observed physiological changes in PCC connectivity in ventral visual stream areas and with PCC/P during the visual task, reflecting the successful involvement of these regions in visual processing. In the MCI group, the PCC connectivity changes were disturbed and remained significant only with the anterior precuneus. In between-group comparison, we observed significant PPI effects in the right superior temporal gyrus in both MCI and AD as compared to HC. This change in connectivity may reflect ineffective “compensatory” mechanism present in the early pre-dementia stages of AD or abnormal modulation of brain connectivity due to the disease pathology. With the disease progression, these changes become more evident but less efficient in terms of compensation. This approach can separate the MCI from HC with 77% sensitivity and 89% specificity.

ID 315 – Altered default mode network connectivity during visual processing in patients with mild cognitive impairment (an fMRI study)

Introduction The object of our study was to detect specific alterations in default mode network (DMN) connectivity when switching from baseline to task condition in 17 patients with mild cognitive impairment (MCI) as compared to 18 healthy controls (HC) and 15 patients with Alzheimer disease (AD) using psychophysiological interactions (PPI) analysis. Methods The fMRI protocol (a complex visual scene-encoding task) was performed using a 1.5 T scanner. PPI analysis was used to assess the effect of the visual task on connectivity with the posterior cingulate/precunes (PCC/P, i.e. the posterior DMN node). Age, gender, education and a measure of atrophy were used as covariates. Results Comparing HC and MCI resulted in a significant difference in the PPI effect in the right superior temporal gyrus (STG) and this difference became stronger in AD. In addition, MCI subjects as compared to AD group showed significant differences in bilateral precuneus. Conclusion and key message We have found specific disturbances in connectivity between the DMN and the ventral visual pathway in MCI patients during the visual processing. These changes were more pronounced in AD patients. Our results indicate the role of the right STG in this pathophysiological mechanism.