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Effect of Dopaminergic Medications on Blood Oxygen Level-Dependent Variability and Functional Connectivity in Parkinson's Disease and Healthy Aging.

ABSTRACT: Both functional connectivity (FC) and blood oxygen level-dependent (BOLD) signal variability (SDBOLD) are methods that are used for examining the physiological state of the brain. Although they are derived from signal changes and are related, a few studies have explored their relationship. Here, we examined the relationship between SDBOLD and FC within the default mode network (DMN) in healthy aging participants and those with Parkinson's disease (PD) ON and OFF dopaminergic medications. Dopaminergic medications had profound effects on both DMN FC and SDBOLD measured separately in PD. Analyzing DMN FC and SDBOLD in a joint independent component analysis, we identified joint components of DMN FC and SDBOLD that were separately associated with measurements of motor and cognitive impairment in PD and qualitatively similar to those in healthy aging. Dopaminergic medications had a differential effect on these components depending on these measures of disease severity, "normalizing" the relationships. Importantly, we show that dopaminergic medication status matters in imaging PD, and it can affect both connectivity and SDBOLD. Imaging PD ON may lead to inflated estimates of SDBOLD and diminish the ability to measure changes associated with declining motor and cognitive capacities.

SUBMITTER: Day TKM

PROVIDER: S-EPMC6727479 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Effect of Dopaminergic Medications on Blood Oxygen Level-Dependent Variability and Functional Connectivity in Parkinson's Disease and Healthy Aging.

Day Trevor K M TKM Madhyastha Tara M TM Lee Adél A Zabetian Cyrus P CP Montine Thomas J TJ Grabowski Thomas J TJ

Brain connectivity 20190901 7

Both functional connectivity (FC) and blood oxygen level-dependent (BOLD) signal variability (SD<sub>BOLD</sub>) are methods that are used for examining the physiological state of the brain. Although they are derived from signal changes and are related, a few studies have explored their relationship. Here, we examined the relationship between SD<sub>BOLD</sub> and FC within the default mode network (DMN) in healthy aging participants and those with Parkinson's disease (PD) ON and OFF dopaminergi ...[more]

PMID: 31131605

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Project description:BackgroundPrevious studies reported increased risk of cardiac events in subjects with fasting blood glucose (FBG) levels lower than the diagnostic threshold of diabetes mellitus. However, whether increased cardiac events in those with upper normal FBG is secondary to the shift of their cardiac sympathovagal balance towards sympathetic predominance is unknown.AimsTo assess the association between FBG levels and cardiac autonomic modulation (CAM) in euglycaemic healthy subjects based on heart rate variability (HRV) derived indices.Subjects and methodsThe study enrolled 42 healthy young adults. Following sociodemographic and clinical assessment, blood samples were collected to measure FBG levels. Five minutes ECG recordings were performed to all participants to obtain frequency domain HRV measurements, namely the natural logarithm (Ln) of total power (LnTP), very low frequency (LnVLF), low frequency (LnLF) and high frequency (LnHF), low frequency/ high frequency ratio (LnLF/HF), normalized low frequency (LF Norm) and high frequency (HF Norm).ResultsFBG levels correlated positively with LnHF (r = 0.33, P = 0.031) and HF Norm (r = 0.35, P = 0.025) and negatively with LF Norm (r = -0.35, P = 0.025) and LnLF/HF (r = -0.33, P = 0.035). LnHF and HF Norm were significantly decreased in subjects with the lower (4.00 (1.34) ms2/Hz and 33.12 (11.94) n.u) compared to those with the upper FBG quartile (5.64 (1.63) ms2/Hz and 49.43 (17.73) n.u, P = 0.013 and 0.032 respectively). LF Norm and LnLF/HF were significantly increased in subjects with the lower (66.88 (11.94) n.u and 0.73 (0.53)) compared to those with the higher FBG quartile (50.58 (17.83) n.u and 0.03 (0.79), P = 0.032 and 0.038 respectively).ConclusionThe present study is the first to demonstrate that rise of blood glucose concentration, within physiological range, is associated with higher parasympathetic, but lower sympathetic CAM. Further researches are needed to set out the glycemic threshold beyond which further increase in glucose level readjusts sympathovagal balance towards sympathetic predominance again.

Project description:Aim: In this work, we propose the novel use of adaptively constrained independent vector analysis (acIVA) to effectively capture the temporal and spatial properties of dynamic blood-oxygen-level-dependent (BOLD) activity (dBA), and we efficiently quantify the spatial property of dBA (sdBA). We also propose to incorporate dBA into the study of brain dynamics to gain insight into activity-connectivity co-evolution patterns. Introduction: Studies of the dynamics of the human brain using functional magnetic resonance imaging (fMRI) have enabled the identification of unique functional network connectivity (FNC) states and provided new insights into mental disorders. There is evidence showing that both BOLD activity, which is captured by fMRI, and FNC are related to mental and cognitive processes. However, a few studies have evaluated the inter-relationships of these two domains of function. Moreover, the identification of subgroups of schizophrenia has gained significant clinical importance due to a need to study the heterogeneity of schizophrenia. Methods: We design a simulation study to verify the effectiveness of acIVA and apply acIVA to the dynamic study of resting-state fMRI data collected from individuals with schizophrenia and healthy controls (HCs) to investigate the relationship between dBA and dynamic FNC (dFNC). Results: The simulation study demonstrates that acIVA accurately captures the spatial variability and provides an efficient quantification of sdBA. The fMRI analysis yields synchronized sdBA-temporal property of dBA (tdBA) patterns and shows that the dBA and dFNC are significantly correlated in the spatial domain. Using these dynamic features, we identify schizophrenia subgroups with significant differences in terms of their clinical symptoms. Conclusion: We find that brain function is abnormally organized in schizophrenia compared with HCs since there are less synchronized sdBA-tdBA patterns in schizophrenia and schizophrenia prefers a component that merges multiple brain regions. Identification of schizophrenia subgroups using dynamic features inspires the use of neuroimaging in studying the heterogeneity of disorders. Impact statement This work introduces the use of joint blind source separation for the study of brain dynamics to enable efficient quantification of the spatial property of dynamic blood-oxygen-level-dependent (BOLD) activity to provide insight into the relationship of dynamic BOLD activity and dynamic functional network connectivity. The identification of subgroups of schizophrenia using dynamic features allows the study of heterogeneity of schizophrenia, emphasizing the importance of functional magnetic resonance imaging analysis in the study of brain activity and functional connectivity to gain a better understanding of the human brain, especially the brain with a mental disorder.

Dataset Information

Effect of Dopaminergic Medications on Blood Oxygen Level-Dependent Variability and Functional Connectivity in Parkinson's Disease and Healthy Aging.

Publications

Effect of Dopaminergic Medications on Blood Oxygen Level-Dependent Variability and Functional Connectivity in Parkinson's Disease and Healthy Aging.

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