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Zuzana Nedelska

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5 papers

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YNIMG Journal 2025 Journal Article

Cardiorespiratory dynamics in the brain: Review on the significance of cardiovascular and respiratory correlates in functional MRI signal

Mahathi Kandimalla
Seokbeen Lim
Jay Thakkar
Sannidhi Dewan
Daehun Kang
Myung-Ho In
Hang Joon Jo
Dong Pyo Jang

Cardiorespiratory signals have long been treated as "noise" in functional magnetic resonance imaging (fMRI) research, with the goal of minimizing their impact to isolate neural activity. However, there is a growing recognition that these signals, once seen as confounding variables, provide valuable insights into brain function and overall health. This shift reflects the dynamic interaction between the cardiovascular, respiratory, and neural systems, which together support brain activity. In this review, we explore the role of cardiorespiratory dynamics-such as heart rate variability (HRV), respiratory sinus arrhythmia (RSA), and changes in blood flow, oxygenation, and carbon dioxide levels-embedded within fMRI signals. These physiological signals reflect critical aspects of neurovascular coupling and are influenced by factors such as physiological stress, breathing patterns, and age-related changes. We also discuss the complexities of distinguishing these signals from neuronal activity in fMRI data, given their significant contribution to signal variability and interactions with cerebrospinal fluid (CSF). Recognizing the influence of these cardiorespiratory dynamics is crucial for improving the interpretation of fMRI data, shedding light on heart-brain and respiratory-brain connections, and enhancing our understanding of circulation, oxygen delivery, and waste elimination within the brain.

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YNIMG Journal 2020 Journal Article

Cholinergic white matter pathways make a stronger contribution to attention and memory in normal aging than cerebrovascular health and nucleus basalis of Meynert

Milan Nemy
Nira Cedres
Michel J. Grothe
J-Sebastian Muehlboeck
Olof Lindberg
Zuzana Nedelska
Olga Stepankova
Lenka Vyslouzilova

The integrity of the cholinergic system plays a central role in cognitive decline both in normal aging and neurological disorders including Alzheimer's disease and vascular cognitive impairment. Most of the previous neuroimaging research has focused on the integrity of the cholinergic basal forebrain, or its sub-region the nucleus basalis of Meynert (NBM). Tractography using diffusion tensor imaging data may enable modelling of the NBM white matter projections. We investigated the contribution of NBM volume, NBM white matter projections, small vessel disease (SVD), and age to performance in attention and memory in 262 cognitively normal individuals (39-77 years of age, 53% female). We developed a multimodal MRI pipeline for NBM segmentation and diffusion-based tracking of NBM white matter projections, and computed white matter hypointensities (WM-hypo) as a marker of SVD. We successfully tracked pathways that closely resemble the spatial layout of the cholinergic system as seen in previous post-mortem and DTI tractography studies. We found that high WM-hypo load was associated with older age, male sex, and lower performance in attention and memory. A high WM-hypo load was also associated with lower integrity of the cholinergic system above and beyond the effect of age. In a multivariate model, age and integrity of NBM white matter projections were stronger contributors than WM-hypo load and NBM volume to performance in attention and memory. We conclude that the integrity of NBM white matter projections plays a fundamental role in cognitive aging. This and other modern neuroimaging methods offer new opportunities to re-evaluate the cholinergic hypothesis of cognitive aging.

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YNICL Journal 2020 Journal Article

The combined effect of amyloid-β and tau biomarkers on brain atrophy in dementia with Lewy bodies

Carla Abdelnour
Daniel Ferreira
Ketil Oppedal
Lena Cavallin
Olivier Bousiges
Lars Olof Wahlund
Jakub Hort
Zuzana Nedelska

BACKGROUND: Alzheimer's disease (AD)-related pathology is frequently found in patients with dementia with Lewy bodies (DLB). However, it is unknown how amyloid-β and tau-related pathologies influence neurodegeneration in DLB. Understanding the mechanisms underlying brain atrophy in DLB can improve our knowledge about disease progression, differential diagnosis, drug development and testing of anti-amyloid and anti-tau therapies in DLB. OBJECTIVES: We aimed at investigating the combined effect of CSF amyloid-β42, phosphorylated tau and total tau on regional brain atrophy in DLB in the European DLB (E-DLB) cohort. METHODS: 86 probable DLB patients from the E-DLB cohort with CSF and MRI data were included. Random forest was used to analyze the association of CSF biomarkers (predictors) with visual rating scales for medial temporal lobe atrophy (MTA), posterior atrophy (PA) and global cortical atrophy scale-frontal subscale (GCA-F) (outcomes), including age, sex, education and disease duration as extra predictors. RESULTS: DLB patients with abnormal MTA scores had abnormal CSF Aβ42, shorter disease duration and older age. DLB patients with abnormal PA scores had abnormal levels of CSF Aβ42 and p-tau, older age, lower education and shorter disease duration. Abnormal GCA-F scores were associated with lower education, male sex, and older age, but not with any AD-related CSF biomarker. CONCLUSIONS: This study shows preliminary data on the potential combined effect of amyloid-β and tau-related pathologies on the integrity of posterior brain cortices in DLB patients, whereas only amyloid-β seems to be related to MTA. Future availability of α-synuclein biomarkers will help us to understand the effect of α-synuclein and AD-related pathologies on brain integrity in DLB.

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YNICL Journal 2019 Journal Article

Characterization of white matter changes along fibers by automated fiber quantification in the early stages of Alzheimer's disease

Xin Zhang
Yu Sun
Weiping Li
Bing Liu
Wenbo Wu
Hui Zhao
Renyuan Liu
Yue Zhang

Brain white matter fiber bundles in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) have abnormalities not usually seen in unaffected subjects. Ideal algorithm of the localization-specific properties in white matter integrity might reveal the changes of tissue properties varying along each tract, while previous studies only detected the mean DTI parameters of each fiber. The aim of this study was to investigate whether these abnormalities of nerve fiber tracts are localized to specific regions of the tracts or spread throughout and to analyze which of the examined fiber tracts are involved in the early stages of Alzheimer's disease. In this study, we utilized VBA, TBSS as well as AFQ together to comprehensively investigate the white matter fiber impairment on 25 CE patients, 29 MCI patients and 34 normal control (NC) subjects. Two tract profiles, fractional anisotropy (FA) and mean diffusivity (MD), were extracted to evaluate the white matter integrity at 100 locations along each of 20 fiber tracts and then we validated the results with 27 CE patients, 21 MCI patients and 22 NC from the ADNI cohort. Also, we compare the AFQ with VBA and TBSS in our cohort. In comparison with NC, AD patients showed widespread FA reduction in 25% (5 /20) and MD increase in 65%(13/20) of the examined fiber tracts. The MCI patients showed a regional FA reduction in 5% (1/20) of the examined fiber tracts (right cingulum cingulate) and MD increase in 5%(1/20) of the examined fiber tracts (left arcuate fasciculus). Among these changed tracts, only the right cingulum cingulate showed widespread disruption of myelin or/and fiber axons in MCI and aggravated deterioration in AD, findings supported by FA/MD changes both by the mean and FA changes by point wise methods and TBSS. And the AFQ findings from ADNI cohort showed some similarity with our cohort, especially in the pointwise comparison of MD profiles between AD vs NC. Furthermore, the pattern of white matter abnormalities was different across neuronal fiber tracts; for example, the MCI and AD patients showed similar FA reduction in the middle part of the right cingulum cingulate, and the anterior part were not damaged. However, the left arcuate fasciculus showed MD elevation located at the temporal part of the fibers in the MCI patients and expanding to the temporal and middle part of the fibers in AD patients. So, the AFQ may be an alternative complementary method of VBA and TBSS, and may provide new insights into white matter degeneration in MCI and its association with AD.

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YNICL Journal 2018 Journal Article

Regional cortical perfusion on arterial spin labeling MRI in dementia with Lewy bodies: Associations with clinical severity, glucose metabolism and tau PET

Zuzana Nedelska
Matthew L. Senjem
Scott A. Przybelski
Timothy G. Lesnick
Val J. Lowe
Bradley F. Boeve
Arvin Arani
Prashanthi Vemuri

Visually preserved metabolism in posterior cingulate cortex relative to hypometabolism in precuneus and cuneus, the cingulate island sign, is a feature of dementia with Lewy bodies (DLB) on FDG-PET. Lower cingulate island sign ratio (posterior cingulate cortex/cuneus+precuneus; FDG-CISr) values have been associated with a higher Braak neurofibrillary tangle stage in autopsied DLB. Using voxel-wise analysis, we assessed the patterns of regional cortical perfusion and metabolism, and using an atlas-based approach, we measured perfusion cingulate island sign ratio on arterial spin labeling MRI (ASL-CISr), and its associations with FDG-CISr, uptake on tau-PET and clinical severity in DLB. Our study sample (n = 114) included clinically probable DLB patients (n = 19), age-matched patients with probable Alzheimer's disease dementia (AD; n = 19) and matched controls (n = 76) who underwent MRI with 3-dimensional pseudo-continuous arterial spin labeling, 18F-FDG-PET and 18F-AV-1451 tau PET. Patterns of cortical perfusion and metabolism were derived from quantitative maps using Statistical Parametric Mapping. DLB patients showed hypoperfusion on ASL-MRI in precuneus, cuneus and posterior parieto-occipital cortices, compared to controls, and relatively spared posterior cingulate gyrus, similar to pattern of hypometabolism on FDG-PET. DLB patients had higher ASL-CISr and FDG-CISr than AD patients (p <0. 001). ASL-CISr correlated with FDG-CISr in DLB patients (r = 0. 67; p =0. 002). Accuracy of distinguishing DLB from AD patients was 0. 80 for ASL-CISr and 0. 91 for FDG-CISr. Lower ASL-CISr was moderately associated with a higher composite medial temporal AV-1451 uptake (r = −0. 50; p =0. 03) in DLB. Lower perfusion in precuneus and cuneus was associated with worse global clinical scores. In summary, the pattern of cortical hypoperfusion on ASL-MRI is similar to hypometabolism on FDG-PET, and respective cingulate island sign ratios correlate with each other in DLB. Non-invasive and radiotracer-free ASL-MRI may be further developed as a tool for the screening and diagnostic evaluation of DLB patients in a variety of clinical settings where FDG-PET is not accessible.

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