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Multimodal multilayer network centrality relates to executive functioning [article]

Lucas C. Breedt, Fernando A.N. Santos, Arjan Hillebrand, Liesbeth Reneman, Anne-Fleur van Rootselaar, Menno M. Schoonheim, Cornelis J. Stam, Anouk Ticheler, Betty Tijms, Dick J. Veltman, Chris Vriend, Margot J. Wagenmakers (+4 others)
2021 bioRxiv   pre-print
Executive functioning is a higher-order cognitive process that is thought to depend on a brain network organization facilitating network integration across specialized subnetworks. The frontoparietal network (FPN), a subnetwork that has diverse connections to other brain modules, seems pivotal to this integration, and a more central role of regions in the FPN has been related to better executive functioning. Brain networks can be constructed using different modalities: diffusion MRI (dMRI) can
more » ... e used to reconstruct structural networks, while resting-state fMRI (rsfMRI) and magnetoencephalography (MEG) yield functional networks. These networks are often studied in a unimodal way, which cannot capture potential complementary or synergistic modal information. The multilayer framework is a relatively new approach that allows for the integration of different modalities into one 'network of networks'. It has already yielded promising results in the field of neuroscience, having been related to e.g. cognitive dysfunction in Alzheimer's disease. Multilayer analyses thus have the potential to help us better understand the relation between brain network organization and executive functioning. Here, we hypothesized a positive association between centrality of the FPN and executive functioning, and we expected that multimodal multilayer centrality would supersede unilayer centrality in explaining executive functioning. We used dMRI, rsfMRI, MEG, and neuropsychological data obtained from 33 healthy adults (age range 22-70 years) to construct eight modality-specific unilayer networks (dMRI, fMRI, and six MEG frequency bands), as well as a multilayer network comprising all unilayer networks. Interlayer links in the multilayer network were present only between a node's counterpart across layers. We then computed and averaged eigenvector centrality of the nodes within the FPN for every uni- and multilayer network and used multiple regression models to examine the relation between uni- or multilayer centrality and executive functioning. We found that higher multilayer FPN centrality, but not unilayer FPN centrality, was related to better executive functioning. To further validate multilayer FPN centrality as a relevant measure, we assessed its relation with age. Network organization has been shown to change across the life span, becoming increasingly efficient up to middle age and regressing to a more segregated topology at higher age. Indeed, the relation between age and multilayer centrality followed an inverted-U shape. These results show the importance of FPN integration for executive functioning as well as the value of a multilayer framework in network analyses of the brain. Multilayer network analysis may particularly advance our understanding of the interplay between different brain network aspects in clinical populations, where network alterations differ across modalities.
doi:10.1101/2021.06.28.450180 fatcat:xofwpq6ftbdlpiwlizkrupihb4

Serotonin transporter occupancy by the SSRI citalopram predicts default-mode network connectivity

Anouk Schrantee, Paul J Lucassen, Jan Booij, Liesbeth Reneman
2018 European Neuropsychopharmacology  
Schrantee). A. Schrantee et al. temporal pole. These findings provide further neurochemical evidence that the serotonin system dose-dependently modulates DMN function.  ... 
doi:10.1016/j.euroneuro.2018.07.099 pmid:30082141 fatcat:zfdfttnxfjhpjlwzgd7w7uwhye

Age-dependent, lasting effects of methylphenidate on the GABAergic system of ADHD patients

Michelle M. Solleveld, Anouk Schrantee, Nicolaas A.J. Puts, Liesbeth Reneman, Paul J. Lucassen
2017 NeuroImage: Clinical  
.; Schrantee, Anouk; Puts, N.A.J.; Reneman, L.; Lucassen, P.J.  ... 
doi:10.1016/j.nicl.2017.06.003 pmid:28725548 pmcid:PMC5506880 fatcat:f5kg7pkcdvhqvdyr3ou3b3ai2q

Assessment of functional shunting in patients with sickle cell disease

Liza Afzali-Hashemi, Lena Václavů, John C. Wood, Bart J. Biemond, Aart J. Nederveen, Henk J.M.M. Mutsaerts, Anouk Schrantee
2022 Haematologica  
Silent cerebral infarcts (SCIs) are common in patients with sickle cell disease (SCD) and are thought to be caused by a mismatch between oxygen delivery and consumption. Functional cerebrovascular shunting is defined as reduced oxygen offloading due to the rapid transit of blood through the capillaries caused by increased flow and has been suggested as a potential mechanism underlying reduced oxygenation and SCI. We investigated the venous arterial spin labeling signal (VS) in the sagittal
more » ... as a proxy biomarker of cerebral functional shunting, and its association with hemodynamic imaging and hematological laboratory parameters. We included 28 children and 38 adults with SCD, and 10 healthy race-matched adult controls. VS, cerebral blood flow (CBF), velocity in the brain feeding arteries, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were measured before and after acetazolamide administration. VS was higher in patients with SCD compared to controls (p
doi:10.3324/haematol.2021.280183 pmid:35548868 fatcat:6kz4hzmttzbezat376hmd73j7a

Dopaminergic System Dysfunction in Recreational Dexamphetamine Users

Anouk Schrantee, Lena Václavů, Dennis F R Heijtel, Matthan W A Caan, Willy Gsell, Paul J Lucassen, Aart J Nederveen, Jan Booij, Liesbeth Reneman
2014 Neuropsychopharmacology  
Schrantee, A.; Václavů, L.; Heijtel, D.F.R.; Caan, M.W.A.; Gsell, W.; Lucassen, P.J.; Nederveen, A.J.; Booij, J.; Reneman, L.  ...  Dopaminergic dysfunction in dexamphetamine users A Schrantee et al subjective responses were rated by measuring the participants' response to an analog self-rating scale that ranged from 1 (not at all)  ...  The challenge with dAMPH induced DA release in the control group by 10.5% Dopaminergic dysfunction in dexamphetamine users A Schrantee et al compared with baseline BP ND (t ¼ 3.936, df ¼ 18, po0.01)  ... 
doi:10.1038/npp.2014.301 pmid:25394786 pmcid:PMC4367461 fatcat:ucbadzj3s5gidoikkpdij4brja

Effects of a single-dose methylphenidate challenge on resting-state functional connectivity in stimulant-treatment naive children and adults with ADHD [article]

Antonia Kaiser, Caroline Broeder, Jessica Cohen, Linda Douw, Liesbeth Reneman, Anouk Schrantee
2022 medRxiv   pre-print
AbstractPrior studies suggest that methylphenidate, the primary pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), alters functional brain connectivity. As the neurotransmitter systems targeted by methylphenidate undergo significant alterations throughout development, the effects of methylphenidate on functional connectivity may also be modulated by age. Therefore, we assessed the effects of a single methylphenidate challenge on brain network connectivity in
more » ... -treatment naïve children and adults with ADHD. We obtained resting-state functional MRI from 50 boys (10-12 years of age) and 49 men (23-40 years of age) with ADHD (DSM IV, all subtypes), before and after an oral challenge with 0.5 mg/kg methylphenidate; and from 11 boys and 12 men as typically-developing controls. Connectivity strength (CS), eigenvector centrality (EC), and betweenness centrality (BC) were calculated for the striatum, thalamus, dorsal anterior cingulate cortex (dACC), and prefrontal cortex (PFC). In line with our hypotheses, we found that methylphenidate decreased measures of connectivity and centrality in the striatum and thalamus in children with ADHD, but increased the same metrics in adults with ADHD. Surprisingly, we found no major effects of methylphenidate in the dACC and PFC in either children or adults. Interestingly, pre-methylphenidate, participants with ADHD showed aberrant connectivity and centrality compared to controls predominantly in frontal regions. Our findings demonstrate that methylphenidate's effects on connectivity of subcortical regions are age-dependent in stimulant-treatment naïve ADHD patients, likely due to ongoing maturation of dopamine and noradrenaline systems. These findings highlight the importance for future studies to take a developmental perspective when studying the effects of methylphenidate treatment.
doi:10.1101/2022.02.04.22270336 fatcat:kzhjela44bd7rmafzcmayzicpa

The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System

Anne Klomp, Jordi L. Tremoleda, Anouk Schrantee, Willy Gsell, Liesbeth Reneman
2012 Journal of Visualized Experiments  
Pharmacological MRI (phMRI) is a new and promising method to study the effects of substances on brain function that can ultimately be used to unravel underlying neurobiological mechanisms behind drug action and neurotransmitter-related disorders, such as depression and ADHD. Like most of the imaging methods (PET, SPECT, CT) it represents a progress in the investigation of brain disorders and the related function of neurotransmitter pathways in a non-invasive way with respect of the overall
more » ... nal connectivity. Moreover it also provides the ideal tool for translation to clinical investigations. MRI, while still behind in molecular imaging strategies compared to PET and SPECT, has the great advantage to have a high spatial resolution and no need for the injection of a contrast-agent or radio-labeled molecules, thereby avoiding the repetitive exposure to ionizing radiations. Functional MRI (fMRI) is extensively used in research and clinical setting, where it is generally combined with a psycho-motor task. phMRI is an adaptation of fMRI enabling the investigation of a specific neurotransmitter system, such as serotonin (5-HT), under physiological or pathological conditions following activation via administration of a specific challenging drug. The aim of the method described here is to assess brain 5-HT function in free-breathing animals. By challenging the 5-HT system while simultaneously acquiring functional MR images over time, the response of the brain to this challenge can be visualized. Several studies in animals have already demonstrated that drug-induced increases in extracellular levels of e.g. 5-HT (releasing agents, selective re-uptake blockers, etc) evoke region-specific changes in blood oxygenation level dependent (BOLD) MRI signals (signal due to a change of the oxygenated/deoxygenated hemoglobin levels occurring during brain activation through an increase of the blood supply to supply the oxygen and glucose to the demanding neurons) providing an index of neurotransmitter function. It has also been shown that these effects can be reversed by treatments that decrease 5-HT availability 16, 13, 18, 7 . In adult rats, BOLD signal changes following acute SSRI administration have been described in several 5-HT related brain regions, i.e. cortical areas, hippocampus, hypothalamus and thalamus 9,16,15 . Stimulation of the 5-HT system and its response to this challenge can be thus used as a measure of its function in both animals and humans 2,11 . Video Link The video component of this article can be found at 1. Anesthetize the rat (male Wistar rat, 200-300 g) with isoflurane (5% induction and then reduced to 1.5-2% for maintenance of anesthesia during animal preparation and scanning) given in medical air (21% O2, BOC UK). Ensure that the animal is well anesthetized and exhibits no response to a toe pinch. The femoral artery and vein are cannulated for blood gas and blood pressure measurements and administration of the drug challenge respectively. During the surgical procedure, the animal's body temperature is monitored and maintained through a rectal probe and a thermal blanket (Harvard apparatus). 2. The anesthetized animal is positioned on a warming pad under a dissecting microscope in dorsal recumbency. Shave the mid-thigh area and swab the skin with alcohol. Make a 2 cm skin incision along the crease formed by the abdomen and right thigh. Blunt dissection of the adductor muscles is used to visualize the femoral artery, vein and the femoral nerve. Separate carefully the vessels. 3. Gently tie a silk ligature completely around the distal end of the vessel and place another tie with half of a surgical knot loosely in the proximal site. Apply traction to both ligatures, to occlude blood flow in the remaining middle portion of the vessel exposed between the ligatures. Make a small incision of about a third of the vessel circumference in this part of the vessel to allow insertion of a PE-50 cannula (0.54 mm internal diameter and 0.96mm for external diameter in case of adult male rats, otherwise 0.40 mm ID and 0.80 mm ED) into the vessel. 4. The cannula should be inserted several mm (at least 5) into the vessel. Once into the lumen, flush a small amount of heparinized saline (15 UI/ml) through the vessel to avoid any formation of blood clot. The proximal silk loop is also ligated completely to fix the cannula. Repeat this April 2012 | 62 | e3956 | procedure for the second vessel. Glue the skin using a Vetbond Tissue Adhesive (3M UK plc, Bracknell, UK) when both cannulas are in place. See Figure 1 for exact placement of the cannulas. 5. Place the animal in a MR compatible stereotactic bed (m2m Imaging Corp., USA) in a prone position. Maintain the head of the animal through the insertion of ear bars and a tooth bar. At this point, the animal can be placed in the MRI scanner for imaging. The animal remains anesthetized and is free-breathing throughout the entire imaging procedure. Preprocessing MRI Data April 2012 | 62 | e3956 | Here we describe several steps in the preprocessing of the MR data in order to optimalize the data for statistical analysis. We mention the tools that are used in our lab, however many different tools are available. Data preparation Motion correction Brain segmentation Data Analysis Goal of the statistical analysis of the MR data is to determine the voxels which exhibit additional variance attributable to the drug challenge in a statistically robust manner. Various methodological approaches are available for this, even as numerable software packages. The choice you make is dependent on the availability of software and knowledge/experience at your lab and your specific research question. Here we give a suggested method as is used in our lab. 6.1 6.2 The next step is then to statistically test the raw 4D time series image of each animal against the previous established GLM model. For this, we used the FSL program FEAT (FMRI Expert Analysis Tool, v5.98) 17,24 . However, other fMRI analysis tools are available as well. Within the analysis tool, a first level analysis has to be set up. This requires the following steps: April 2012 | 62 | e3956 |
doi:10.3791/3956 pmid:22565099 pmcid:PMC3466645 fatcat:pwl7kaskg5f4rp5ctitbeagkji

Cerebral [18F]-FDOPA Uptake in Autism Spectrum Disorder and Its Association with Autistic Traits

Rik Schalbroeck, Lioe-Fee de Geus-Oei, Jean-Paul Selten, Maqsood Yaqub, Anouk Schrantee, Therese van Amelsvoort, Jan Booij, Floris H. P. van Velden
2021 Diagnostics  
Dopaminergic signaling is believed to be related to autistic traits. We conducted an exploratory 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine positron emission tomography/computed tomography ([18F]-FDOPA PET/CT) study, to examine cerebral [18F]-FDOPA influx constant (kicer min−1), reflecting predominantly striatal dopamine synthesis capacity and a mixed monoaminergic innervation in extrastriatal neurons, in 44 adults diagnosed with autism spectrum disorder (ASD) and 22 controls, aged 18 to 30
more » ... ars. Autistic traits were assessed with the Autism Spectrum Quotient (AQ). Region-of-interest and voxel-based analyses showed no statistically significant differences in kicer between autistic adults and controls. In autistic adults, striatal kicer was significantly, negatively associated with AQ attention to detail subscale scores, although Bayesian analyses did not support this finding. In conclusion, among autistic adults, specific autistic traits can be associated with reduced striatal dopamine synthesis capacity. However, replication of this finding is necessary.
doi:10.3390/diagnostics11122404 pmid:34943640 pmcid:PMC8700159 fatcat:74up76dndnfyhlsah2mn4cnepu

GABA, Glutamate, and NAA Levels in the Deep Cerebellar Nuclei of Essential Tremor Patients

Arthur W G Buijink, Naomi Prent, Nicolaas A Puts, Anouk Schrantee, Wouter V Potters, Anne-Fleur van Rootselaar
2021 Frontiers in Neurology  
Essential tremor is among the commonly observed movement disorders in clinical practice, however the exact pathophysiological mechanisms underlying tremor are unknown. It has been suggested that Purkinje cell alterations play a causal factor in tremorgenesis. Altered levels of inhibitory (GABA) and excitatory (glutamate+glutamine, Glx) neurotransmitters could be markers for Purkinje cell alterations. We hypothesize that GABA and Glx levels in the dentate nuclei could be differentially altered
more » ... patients responsive to either anticonvulsants or β-adrenergic blockers. Methods: In this explorative study in patients with essential tremor, we measured gamma-aminobutyric acid (GABA) and glutamate+glutamine (Glx) levels in the dentate nucleus region using 1H-magnetic resonance spectroscopy (MRS) in seven patients using propranolol, five patients using anticonvulsants, and eight healthy controls. Results: There were no group differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. There was no correlation with tremor severity. Discussion: Our results are in line with previously published studies; however, additional studies on a larger number of patients are warranted to confirm these findings. Furthermore medication-subgroups did not exhibit differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. A recent study, of similar size, found an inverse association between tremor severity and the GABA+/Glx ratio in the cerebellum of essential tremor patients. We were unable to replicate these findings. The field of tremor research is plagued by heterogeneous results, and we would caution against drawing firm conclusions based on pilot studies.
doi:10.3389/fneur.2021.664735 pmid:34025569 pmcid:PMC8136412 fatcat:7rwjev4onreevk2pk7dcj4l2r4

Effects of dexamphetamine-induced dopamine release on resting-state network connectivity in recreational amphetamine users and healthy controls

Anouk Schrantee, Bart Ferguson, Diederick Stoffers, Jan Booij, Serge Rombouts, Liesbeth Reneman
2015 Brain Imaging and Behavior  
The results of the SPECT study in this cohort are more elaborately reported elsewhere (Schrantee et al. 2014) .  ...  The few studies that have been conducted in humans reported lower striatal DAT binding and reduced striatal DA release in response to acute dAMPH administration (Schrantee et al. 2014; Reneman et al.  ... 
doi:10.1007/s11682-015-9419-z pmid:26149196 pmcid:PMC4908160 fatcat:4xn542p2svckhfc23dmumcxoci

ADHD and maturation of brain white matter: A DTI study in medication naive children and adults

Cheima Bouziane, Matthan W.A. Caan, Hyke G.H. Tamminga, Anouk Schrantee, Marco A. Bottelier, Michiel B. de Ruiter, Sandra J.J. Kooij, Liesbeth Reneman
2018 NeuroImage: Clinical  
A B S T R A C T Several diffusion tensor imaging (DTI) studies in attention deficit hyperactivity disorder (ADHD) have shown a delay in brain white matter (WM) development. Because these studies were mainly conducted in children and adolescents, these WM abnormalities have been assumed, but not proven to progress into adulthood. To provide further insight in the natural history of WM maturation delay in ADHD, we here investigated the modulating effect of age on WM in children and adults. 120
more » ... mulant-treatment naive male ADHD children (10-12 years of age) and adults (23-40 years of age) with ADHD (according to DSM-IV; all subtypes) were included, along with 23 age and gender matched controls. Fractional anisotropy (FA) values were compared throughout the WM by means of tract-based spatial statistics (TBSS) and in specific regions of interest (ROIs). On both TBSS and ROI analyses, we found that stimulanttreatment naive ADHD children did not differ in FA values from control children, whereas adult ADHD subjects had reduced FA values when compared to adult controls in several regions. Significant age × group interactions for whole brain FA (p = 0.015), as well as the anterior thalamic radiation (p = 0.015) suggest that ADHD affects the brain WM age-dependently. In contrast to prior studies conducted in medicated ADHD children, we did not find WM alterations in stimulant treatment naïve children, only treatment-naïve adults. Thus, our findings suggest that the reported developmental delay in WM might appear after childhood, and that previously reported differences between ADHD children and normal developing peers could have been attributed to prior ADHD medications, and/or other factors that affect WM development, such as age and gender.
doi:10.1016/j.nicl.2017.09.026 pmid:29527472 pmcid:PMC5842546 fatcat:tw6r75mfs5f2lpxizqkrbpljam

The social instability stress paradigm in rat and mouse: A systematic review of protocols, limitations, and recommendations

Amber Koert, Annemie Ploeger, Claudi L.H. Bockting, Mathias V. Schmidt, Paul J. Lucassen, Anouk Schrantee, Joram D. Mul
2021 Neurobiology of Stress  
Social stress is an important environmental risk factor for the development of psychiatric disorders, including depression and anxiety disorders. Social stress paradigms are commonly used in rats and mice to gain insight into the pathogenesis of these disorders. The social instability stress (SIS) paradigm entails frequent (up to several times a week) introduction of one or multiple unfamiliar same-sex home-cage partners. The subsequent recurring formation of a new social hierarchy results in
more » ... ronic and unpredictable physical and social stress. We compare and discuss the stress-related behavioral and physiological impact of SIS protocols in rat and mouse, and address limitations due to protocol variability. We further provide practical recommendations to optimize reproducibility of SIS protocols. We conducted a systematic review in accordance with the PRISMA statement in the following three databases: PubMed, Web of Science and Scopus. Our search strategy was not restricted to year of publication but was limited to articles in English that were published in peer-reviewed journals. Search terms included "social* instab*" AND ("animal" OR "rodent" OR "rat*" OR "mice" OR "mouse"). Thirty-three studies met our inclusion criteria. Fifteen articles used a SIS protocol in which the composition of two cage mates is altered daily for sixteen days (SIS16D). Eleven articles used a SIS protocol in which the composition of four cage mates is altered twice per week for 49 days (SIS49D). The remaining seven studies used SIS protocols that differed from these two protocols in experiment duration or cage mate quantity. Behavioral impact of SIS was primarily assessed by quantifying depressive-like, anxiety-like, social-, and cognitive behavior. Physiological impact of SIS was primarily assessed using metabolic parameters, hypothalamus-pituitary-adrenal axis activity, and the assessment of neurobiological parameters such as neuroplasticity and neurogenesis. Both shorter and longer SIS protocols induce a wide range of stress-related behavioral and physiological impairments that are relevant for the pathophysiology of depression and anxiety disorders. To date, SIS16D has only been reported in rats, whereas SIS49D has only been reported in mice. Given this species-specific application as well as variability in reported SIS protocols, additional studies should determine whether SIS effects are protocol duration- or species-specific. We address several issues, including a lack of consistency in the used SIS protocols, and suggest practical, concrete improvements in design and reporting of SIS protocols to increase standardization and reproducibility of this etiologically relevant preclinical model of social stress.
doi:10.1016/j.ynstr.2021.100410 pmid:34926732 pmcid:PMC8648958 fatcat:zhl7xkbdubasdkvuc6lzzfd6ju

Dose-dependent effects of the selective serotonin reuptake inhibitor citalopram: A combined SPECT and phMRI study

Anouk Schrantee, Michelle M Solleveld, Hilde Schwantje, Willem B Bruin, Henk-Jan MM Mutsaerts, Sofie M Adriaanse, Paul Lucassen, Jan Booij, Liesbeth Reneman
2019 Journal of Psychopharmacology  
ORCID iDs Anouk Schrantee https://orcid.org/0000-0002-4035-4845 Henk-Jan MM Mutsaerts https://orcid.org/0000-0003-0894-0307  ... 
doi:10.1177/0269881119836229 pmid:30887865 pmcid:PMC6572584 fatcat:fwmmbhoqf5geloeljtmprq4rha

The influence of age-of-onset of antidepressant use on the acute CBF response to a citalopram challenge; a pharmacological MRI study

Michelle M. Solleveld, Anouk Schrantee, Judith R. Homberg, Paul J. Lucassen, Liesbeth Reneman
2020 Psychiatry Research : Neuroimaging  
effect of the citalopram challenge on the thalamus across the whole sample; whereas another study by our group in healthy controls did find a significant phMRI response to citalopram in the thalamus (Schrantee  ... 
doi:10.1016/j.pscychresns.2020.111126 pmid:32592855 fatcat:tdt2hhebcrgz3axihi462nl4m4

Impairment of Cerebrovascular Hemodynamics in Patients With Severe and Milder Forms of Sickle Cell Disease

Liza Afzali-Hashemi, Koen P. A. Baas, Anouk Schrantee, Bram F. Coolen, Matthias J. P. van Osch, Stefan M. Spann, Erfan Nur, John C. Wood, Bart J. Biemond, Aart J. Nederveen
2021 Frontiers in Physiology  
In patients with sickle cell disease (SCD), cerebral blood flow (CBF) is elevated to counteract anemia and maintain oxygen supply to the brain. This may exhaust the vasodilating capacity of the vessels, possibly increasing the risk of silent cerebral infarctions (SCI). To further investigate cerebrovascular hemodynamics in SCD patients, we assessed CBF, arterial transit time (ATT), cerebrovascular reactivity of CBF and ATT (CVRCBF and CVRATT) and oxygen delivery in patients with different forms
more » ... of SCD and matched healthy controls. We analyzed data of 52 patients with severe SCD (HbSS and HbSβ0-thal), 20 patients with mild SCD (HbSC and HbSβ+-thal) and 10 healthy matched controls (HbAA and HbAS). Time-encoded arterial spin labeling (ASL) scans were performed before and after a vasodilatory challenge using acetazolamide (ACZ). To identify predictors of CBF and ATT after vasodilation, regression analyses were performed. Oxygen delivery was calculated and associated with hemoglobin and fetal hemoglobin (HbF) levels. At baseline, severe SCD patients showed significantly higher CBF and lower ATT compared to both the mild SCD patients and healthy controls. As CBFpostACZ was linearly related to CBFpreACZ, CVRCBF decreased with disease severity. CVRATT was also significantly affected in severe SCD patients compared to mild SCD patients and healthy controls. Considering all groups, women showed higher CBFpostACZ than men (p < 0.01) independent of baseline CBF. Subsequently, post ACZ oxygen delivery was also higher in women (p < 0.05). Baseline, but not post ACZ, GM oxygen delivery increased with HbF levels. Our data showed that baseline CBF and ATT and CVRCBF and CVRATT are most affected in severe SCD patients and to a lesser extent in patients with milder forms of SCD compared to healthy controls. Cerebrovascular vasoreactivity was mainly determined by baseline CBF, sex and HbF levels. The higher vascular reactivity observed in women could be related to their lower SCI prevalence, which remains an area of future work. Beneficial effects of HbF on oxygen delivery reflect changes in oxygen dissociation affinity from hemoglobin and were limited to baseline conditions suggesting that high HbF levels do not protect the brain upon a hemodynamic challenge, despite its positive effect on hemolysis.
doi:10.3389/fphys.2021.645205 pmid:33959037 pmcid:PMC8093944 fatcat:uxar56xvirhqparj7aihppyrja
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