Biology subjects

Rezaei, A.

Publications and source records attributed to Rezaei, A..

12 recordsLinked to original sources

bioRxiv2026

Physics and Morphology Constrained Quantitative Susceptibility Based Segmentation of Cerebral Veins

Purpose: Quantitative susceptibility mapping (QSM) provides venous contrast through the paramagnetic susceptibility of deoxyhemoglobin and can be used to estimate oxygen extraction fraction (OEF), a marker of cerebral metabolism. However, cerebral vein segmentation remains challenging due to artifacts, variability across QSM reconstruction methods, and limited sensitivity of conventional vessel-filtering approaches to small cortical veins. This study proposes a physics- and morphology-constrained deep learning framework for cerebral vein segmentation on QSM. Methods: Thirty subjects were manually segmented and used to train an attention-gated UNet. In addition to supervised Dice and cross-entropy losses, the network incorporated two selfsupervised constraints. A physics-informed loss enforced consistency between the measured local field and a field simulated from predicted veins using dipole convolution. A Frangi vesselness loss encouraged anatomically plausible tubular structures. Segmentation performance was evaluated on an independent multi-center cohort and compared with a prior vessel-filtering method and a supervised U-Net baseline. Physiological relevance was assessed by comparing QSM-derived venous OEF with calibrated fMRI-derived OEF. Results: The proposed model achieved superior segmentation performance (centreline Dice = 0.70 {+/-} 0.08) compared with MSVF (0.44 {+/-} 0.09) and the U-Net baseline (0.57 {+/-} 0.14). Improvements were most pronounced in smaller veins, resulting in greater vessel continuity. Venous OEF derived from the proposed framework demonstrated stronger agreement with calibrated fMRI-derived OEF than the previous approach. Conclusion: Combining supervised learning with physics- and morphology-based constraints improves vein segmentation and enhances the sensitivity of QSM-derived OEF measurements. Code and model weights are publicly available at https://github.com/QuantitativePhysiologyImagingLab/VeinSeg

biophysics↗

bioRxiv2026

Transcranial Magnetic Stimulation Differentiates Egocentric vs. Allocentric Network Hubs for Memory-Guided Reach

Previous patient and imaging studies suggest that dorsal and ventral visual stream mechanisms contribute selectively to egocentric (eye-centred) and allocentric (landmark-centred) goal-directed behaviours, respectively. However, causal evidence for this ego-allocentric dissociation in healthy brains is lacking. Based on a recent neuroimaging study, we hypothesized that perturbations to dorsal stream network hubs would disrupt both egocentric and allocentric reaches, whereas perturbations to ventral hubs would affect only allocentric reaches. Sixteen participants viewed a briefly presented target in the presence of a landmark that later shifted after a memory interval. Participants were instructed to 1) ignore the landmark and reach toward / opposite the original target location (egocentric task) or 2) reach toward the targets location fixed relative to the shifted landmark (allocentric task). Transcranial magnetic stimulation (TMS) was applied during the memory period, spanning the landmark shift, at two occipital sites, based on the network hub coordinates from our previous study and individual brain anatomy. As predicted, superior occipital TMS impaired reaction time, accuracy, and precision in both tasks, whereas inferior occipital TMS only impaired allocentric performance. Further, spatial asymmetries in the resulting error patterns were influenced by TMS site and task: superior occipital TMS influenced asymmetries more strongly in the egocentric task, whereas inferior occipital TMS only influenced spatial asymmetries in the allocentric task. Finally, a functional network analysis revealed a widespread influence of TMS on network-behavior relations and another dissociation: greater influence of superior occipital TMS on the egocentric task and of inferior occipital TMS on the allocentric task. These results establish specific causal relationships between occipital hubs, widespread cortical networks, and reach behavior, confirming a default dorsal egocentric transformation for visually aimed reaches, and a role for the ventral stream for landmark-centred actions.

neuroscience↗

bioRxiv2026

A shared functional architecture for error-based and reinforcement-based motor learning in the human brain

The motor system can flexibly learn from fundamentally different teaching signals, from directional errors to rewards. While computational and neurobiological models have long assigned these to distinct error-based learning (EL) and reinforcement-based learning (RL) processes, whether this separation holds at the level of whole-brain network architecture has not been directly tested. Here, we characterized whole-brain functional connectivity manifolds in the same participants as they performed separate EL and RL motor tasks -- differing in both feedback type and motor structure -- during two fMRI sessions. By jointly embedding covariance patterns from both tasks into a common low-dimensional neural space, we isolated task-general from task-specific learning-related network reconfigurations. We show that both forms of motor learning induce converging changes in the manifold structure of higher-order transmodal cortex, with comparatively limited task-specific modulation. Notably, this convergence extended to the cerebellum and basal ganglia, the canonical substrates of error-based and reward-based learning, which reconfigured comparably across both tasks. Against this shared backdrop, we found that the posterior medial cortex exhibited a unique functional geometry, selectively redistributing its connectivity across distinct brain circuits depending on feedback type and learning stage. We further demonstrate that individual differences in domain-general motor learning ability are associated with stage-dependent reconfigurations within limbic, default-mode, and attentional systems. These findings indicate that flexible motor adaptation, irrespective of the nature of the learning signal, is supported less by changes within task-specific sensorimotor circuits than by the dynamic reorganization of higher-order brain networks that coordinate them.

neuroscience↗

bioRxiv2026

Regional distribution of white matter hyperintensity burden in coronary artery disease and links with coronary revascularization procedure

IntroductionCoronary artery disease (CAD) increases the risk of cerebrovascular events, yet early brain injury in this population remains poorly characterized. White matter hyperintensities (WMHs), a biomarker of cerebrovascular lesions, are prevalent in CAD and are linked to risk of stroke. Beyond total burden, spatial distribution of WMHs carries pathological significance and is critical for understanding CAD-related injury. While clinical outcomes including coronary revascularization procedure and myocardial infarction influence CAD prognosis, their impact on WMH burden remains unclear. MethodsThis study investigated regional WMH burden in CAD and its relationship with clinical characteristics. 82 adults over 50 years participated, including 44 individuals with CAD and 38 controls. WMHs were segmented from fluid attenuated inversion recovery and T1-weighted MRI and categorized as total, periventricular, deep, and superficial regions. History of myocardial infarction and coronary revascularization (coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI)), was obtained from medical files. ResultsIndividuals with CAD exhibited higher total, periventricular, and deep WMH volumes than controls. Participants who underwent CABG had higher superficial WMH volumes than those with PCI, suggesting greater disease severity influences WMH burden. ConclusionCAD is characterized by a distinct pattern of cerebrovascular vulnerability, with revascularization procedures influencing WMH burden

neuroscience↗

bioRxiv2026

Coronary artery disease is linked with demyelination and iron deposition in white matter watershed areas

Coronary artery disease increases risk of cognitive decline and stroke and is associated with white matter alterations. However, the biological basis of these changes remains unclear. Myelin content and iron deposition are crucial measures of white matter health and can be measured with quantitative MRI. This study investigated whether myelin and iron alterations occur in coronary artery disease, and their relationship with cognition. In this cross-sectional study, 46 individuals with coronary artery disease and 40 healthy controls aged > 50 years, with normal cognition underwent 3T MRI and cognitive assessments. Quantitative MRI metrics (susceptibility, magnetization transfer saturation, R2* and R1 relaxation rates) were calculated in the border zones between adjacent arterial territories (watershed regions) and in the areas outside these borders (non-watershed regions). Relative to controls, the coronary artery disease group showed lower myelin and higher iron content, as measured by lower magnetization transfer saturation and R1, and higher susceptibility specifically in watershed regions. Importantly, these microstructural alterations were associated with poorer cognitive performance in the coronary artery disease group with lower magnetization transfer and R1related to poorer global cognition and with higher magnetic susceptibility with poorer verbal memory. These findings suggest that coronary artery disease is associated with demyelination and iron deposition in white matter, most prominently in watershed regions, which are known for their susceptibility to stroke. The association of these microstructural alterations with cognition highlights the role of white matter as a key vulnerable region and a promising focus for future mechanistic and therapeutic studies.

neuroscience↗

bioRxiv2025

Greater cardiorespiratory fitness is associated with higher cerebral blood flow and lower oxygen extraction fraction in healthy older adults

Aerobic exercise training promotes cardiovascular, brain and cognitive health. Regular exercise is associated with higher cardiorespiratory fitness, commonly assessed by peak oxygen uptake (VO2peak) during maximal effort testing. Higher cardiorespiratory fitness has been linked to preserved brain health, particularly higher grey matter volume and perfusion. The brain relies heavily on oxidative metabolism, yet the relationship between cardiorespiratory fitness and brain oxidative metabolism remains underexplored. This study investigated the association between VO2peak and two key cerebral metabolic parameters: the cerebral metabolic rate of oxygen consumption (CMRO2) and oxygen extraction fraction (OEF), which represents the balance between cerebral blood flow (CBF) and CMRO2. Thirty-seven healthy adults aged [≥]50 underwent maximal cardiopulmonary exercise testing for VO2peak assessment. Neuroimaging included dual calibrated functional MRI (dc-fMRI) and quantitative susceptibility mapping (QSM). Higher VO2peak correlated positively with higher CBF across whole-brain grey matter but showed no relationship with CMRO2. Conversely, higher VO2peak negatively correlated with lower OEF from both dc-fMRI and QSM. These findings suggest that greater cardiorespiratory fitness enhances cerebral perfusion without changing resting metabolic rate in healthy older adults, resulting in a reduced oxygen extraction. These results are consistent with exercise yielding improved vascular- metabolic coupling, which would reduce the likelihood of transient hypoxic episodes.

biophysics↗

bioRxiv2025

Preservation of cerebral vascular and metabolic health with greater cardiorespiratory fitness in coronary artery disease

BackgroundCoronary artery disease (CAD) is the leading cause of cardiovascular-related death globally. Beyond its cardiac consequences, CAD significantly impacts brain health, causing grey matter atrophy, reduced cerebral blood flow (CBF), impaired cerebrovascular reactivity (CVR), and cognitive decline. Recent evidence also highlights altered cerebral metabolism in CAD, characterized by reduced cerebral metabolic rate of oxygen consumption (CMRO2) and increased oxygen extraction fraction (OEF). Notably, impaired cardiorespiratory fitness, as measured by reduced peak oxygen uptake (VO2peak), is a hallmark of CAD progression and a strong prognostic marker of cardiovascular and neurological outcomes. Although VO2peak is associated with brain structural integrity and cognitive function, its relationship to cerebral vascular and metabolic function in CAD patients remains poorly understood. MethodsThirty-seven healthy individuals (age=65.35 {+/-} 8.31) and thirty-five patients with CAD (age=66.42 {+/-} 9.29) participated in this study. The objective was to determine whether higher cardiorespiratory fitness is associated with markers of cerebral health known to be impaired in CAD, in order to assess the potential of exercise as a strategy to mitigate CAD-related brain alterations. Cerebral vascular and metabolic biomarkers, including CBF, CVR, CMRO2, and OEF, were quantified using calibrated functional magnetic resonance imaging (MRI). Participants also completed a maximal cardiopulmonary exercise test on a bicycle ergometer to determine peak oxygen uptake (VO2peak). ResultsAcross all participants, VO2peak was positively associated with CBF ({beta}=0.32, p=0.02), and CVR ({beta}=0.002, p=0.04), in grey matter, confirming a link between aerobic fitness and vascular health across the cardiovascular health spectrum. However, metabolic markers exhibited group-specific patterns. Specifically, in CAD patients, VO2peak was positively associated with CMRO2 ({beta} = 0.08, p = 0.02), suggesting that reduced CMRO2 in CAD may be partially preserved by greater cardiorespiratory fitness. In contrast, a negative association between VO2peak and OEF was observed exclusively in healthy controls ({beta} = -3.6, p = 0.02), consistent with adaptations in healthy aging being primarily driven by improved CBF without changes in CMRO2. ConclusionThis study shows that higher cardiorespiratory fitness is associated with improved cerebral vascular and metabolic function, with distinct patterns observed between healthy individuals and those with CAD. In patients with CAD, greater fitness appears to preserve cerebral oxygen metabolism, while in healthy individuals, fitness is primarily linked to enhanced perfusion. These findings support the role of aerobic exercise as a promising strategy to counteract CAD-related brain alterations, emphasizing the importance of targeting cardiorespiratory fitness in both prevention and rehabilitation settings.

biophysics↗

bioRxiv2025

Direct binding of TDP-43 and Tau drives their co-condensation, but suppresses Tau fibril formation and seeding

Neuronal Tau aggregates are a hallmark of Alzheimers disease (AD), but more than half of the patients exhibit additional TDP-43 inclusions and some have co-aggregates of both proteins. The presence of Tau/TDP-43 co-pathology is associated with increased disease severity, although the causal relationship remains unclear. Here we demonstrate that Tau and TDP-43 mutually promote each others condensation through direct interaction in vitro, forming irregularly shaped or multiphasic co-condensates with lower TDP-43 mobility, but higher Tau dynamics. While Tau promotes TDP-43 aggregation in vitro, TDP-43 suppresses formation of Tau fibrils and instead causes formation of oligomeric Tau and Tau/TDP-43 species. These co-assemblies hinder Tau seeding in a biosensor assay specific for proteopathic Tau seeds. Consistent with this data, SarkoSpin extracts from AD brains with Tau/TDP-43 co-pathology exhibit reduced Tau seeding compared to Tau-only AD brains. In contrast, patient-derived extracts from AD brains with Tau/TDP-43 co-pathology are highly potent in seeding TDP-43 neoaggregates in a TDP-43 reporter cell line. Our results suggest that direct interaction of TDP-43 and Tau may suppress Tau pathology, while promoting TDP-43 pathology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/662960v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1ed5dfaorg.highwire.dtl.DTLVardef@b4ef07org.highwire.dtl.DTLVardef@b8dbe8org.highwire.dtl.DTLVardef@6d9b49_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

The Impact of Coronary Artery Disease on Brain Vascular and Metabolic Health: Links to Cognitive Function

BackgroundCoronary artery disease (CAD) is the leading cause of mortality worldwide and is associated with an increased incidence of cognitive decline, however the pathological mechanisms linking CAD to brain and cognitive health remain unclear. Prior research has identified regional deficits in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), a measure of vascular reserve, in patients with CAD. However, the impact of these cerebrovascular deficits on cognition has not been explored, nor has the effect of CAD on cerebral metabolic health. This study aims to fill these gaps by investigating how CAD influences cerebral vascular and metabolic health, and how these alterations relate to cognitive function across multiple domains. MethodsQuantitative magnetic resonance imaging (MRI) was employed to measure a comprehensive profile of cerebral vascular and metabolic health, including CBF, CVR, cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF). Cognition was assessed using a validated neuropsychological battery from which composite scores were extracted, reflecting executive functions, working memory, processing speed, and verbal episodic memory. ResultsA total of 35 patients with CAD and 37 healthy controls were included in the final analysis. Patients with CAD demonstrated widespread impairments in both cerebral vascular and metabolic health, characterized by lower CBF, CVR, and CMRO2, and increased OEF, indicative of insufficient oxygen delivery. Notably, lower CVR was associated with poorer executive function, suggesting a specific role of vascular reserve for preserving executive functions. Furthermore, higher OEF was associated with poorer working memory, showing the importance of preserved oxygen consumption for maintaining cognitive function. ConclusionThis study reveals that CAD is associated with impaired cerebral vascular and metabolic health, providing a pathological basis for cognitive decline. Specifically, reduced CVR and elevated OEF emerged as sensitive biomarkers linking impaired brain health and cognition. These markers hold promise for guiding future interventions aimed at preserving cognitive health in patients with CAD. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LICoronary artery disease is associated with an increased incidence of cognitive decline but the biological mechanisms underlying these changes in cognition are unclear. C_LIO_LIThis is the first study to comprehensively demonstrate profound and widespread deficits in both cerebral vascular and oxidative metabolic health in patients with coronary artery disease. C_LIO_LICerebrovascular reactivity and oxygen extraction fraction may be sensitive biomarkers of early cognitive decline in coronary artery disease. C_LI What Are the Clinical Implications?O_LIThe widespread impairments in cerebral vascular and metabolic health suggest that coronary artery disease has profound consequences on the brain. C_LIO_LIPoor vascular reserve and an imbalance between oxygen delivery and usage may be crucial determinants of cognitive health. These results highlight the limitations of traditional biomarkers in understanding the brains vulnerability and the need for these novel and quantitative biomarkers of cerebral physiological health. C_LIO_LIThese findings suggest that cerebral vascular and metabolic deficits exist even in the absence of overt cognitive decline in coronary artery disease, emphasizing the need for early detection and preventative strategies. C_LI

biophysics↗

bioRxiv2025

Multivariate white matter microstructure alterations in older adults with coronary artery disease

Patients with coronary artery disease (CAD) face an increased risk of cognitive impairment, dementia, and stroke. While white matter (WM) lesions are frequently reported in patients with CAD, the effects on WM microstructure alterations remain largely unknown. We aimed to identify WM microstructural alterations in individuals with CAD compared to healthy controls (HC), and to examine their relationships with cognitive performance. Forty-three (43) patients with CAD and 36 HC aged 50 and older underwent comprehensive neuropsychological testing and multi-modal 3T MRI. A novel multivariate approach - the Mahalanobis distance (D2) - was used to quantify WM abnormalities as the amount of deviation from the HC reference group. D2 integrates multiple MRI-derived diffusion-weighted imaging, R1 relaxometry, and magnetization transfer imaging metrics, while accounting for covariance between metrics. Relationships between WM D2 and cognition (executive function and processing speed) were also assessed. Compared to HCs, patients with CAD had higher D2 values in the whole WM (p=0.009) and in the territories right anterior, bilateral middle, and right posterior cerebral artery territories (p<0.05). Myelin-sensitive metrics, particularly R1 relaxation rate and MT saturation (MTsat), were the most important contributors to D2. Processing speed was positively associated with greater R1 in both the whole WM and left middle cerebral artery territory. These findings suggest that greater WM microstructural alterations observed in patients with CAD were mainly driven by differences in myelin content, as R1 and MTsat were the most important contributors. These alterations may contribute to a heightened risk of cognitive impairment.

neuroscience↗

bioRxiv2022

Protective effects of different doses of MitoQ separately and combined with trehalose on sperm function and antioxidative status of cryopreserved Markhoz goat semen

The mitochondria-targeted antioxidant MitoQ has been regarded as an effective antioxidant agent against cryo-induced oxidative cellular damage. This study aimed to evaluate the use of different doses of MitoQ combined with trehalose to minimize mitochondrial impairment and oxidative stress during sperm cryopreservation of Markhoz goat. For this, semen collection was performed every 5 days from 5 bucks (10 ejaculates per buck). The ejaculates were pooled and then diluted in eight different Tris-based extenders as follows: no additives (control), 20, 200, 2000 nM of MitoQ (MT20, MT200, MT 2000, respectively), 150 mM of trehalose (Tr), MT20+Tr, MT200+Tr, MT2000+Tr. Each semen sample was frozen using a standard protocol, and sperm function and antioxidative status were evaluated after thawing. Results indicated higher total and progressive motility, acrosome and membrane integrity, superoxide dismutase, glutathione peroxidase, total antioxidant capacity, and lower DNA fragmentation and malondialdehyde in MT200+Tr than for all other groups except MT200; meanwhile, MT200 was also greater in these parameters than in the control group (P < 0.05). Furthermore, MT200 and MT200+Tr showed higher (P < 0.05) percentages of live cryopreserved sperm with high membrane mitochondrial potential than other groups. However, abnormality percentage and catalase activity of frozen-thawed sperm were not affected by treatments (P > 0.05). To conclude, we have found that supplementation of 200 nM MitoQ alone or in combination with 150 mM trehalose to semen extender improves the quality of cryopreserved sperm in goats, which is associated with enhanced antioxidant enzymatic defense and mitochondrial activity and reduced DNA fragmentation.

cell biology↗

bioRxiv2021

Proteomic signature of the Dravet syndrome in the genetic Scn1a-A1783V mouse model

BackgroundDravet syndrome is a rare, severe pediatric epileptic encephalopathy associated with intellectual and motor disabilities. Proteomic profiling in a mouse model of Dravet syndrome can provide information about the molecular consequences of the genetic deficiency and about pathophysiological mechanisms developing during the disease course. MethodsA knock-in mouse model of Dravet syndrome with Scn1a haploinsufficiency was used for whole proteome, seizure and behavioral analysis. Hippocampal tissue was dissected from two-(prior to epilepsy manifestation) and four-(following epilepsy manifestation) week-old male mice and analyzed using LC-MS/MS with label-free quantification. Proteomic data sets were subjected to bioinformatic analysis including pathway enrichment analysis. The differential expression of selected proteins was confirmed by immunohistochemical staining. ResultsThe findings confirmed an increased susceptibility to hyperthermia-associated seizures, the development of spontaneous seizures, and behavioral alterations in the novel Scn1a-A1873V mouse model of Dravet syndrome. As expected, proteomic analysis demonstrated more pronounced alterations following epilepsy manifestation. In particular, proteins involved in neurotransmitter dynamics, receptor and ion channel function, synaptic plasticity, astrogliosis, neoangiogenesis, and nitric oxide signaling showed a pronounced regulation in Dravet mice. Pathway enrichment analysis identified several significantly regulated pathways at the later time point, with pathways linked to synaptic transmission and glutamatergic signaling dominating the list. ConclusionIn conclusion, the whole proteome analysis in a mouse model of Dravet syndrome demonstrated complex molecular alterations in the hippocampus. Some of these alterations may have an impact on excitability or may serve a compensatory function, which, however, needs to be further confirmed by future investigations. The proteomic data indicate that, due to the molecular consequences of the genetic deficiency, the pathophysiological mechanisms may become more complex during the course of the disease. Resultantly, the management of Dravet syndrome may need to consider further molecular and cellular alterations. Ensuing functional follow-up studies, this data set may provide valuable guidance for the future development of novel therapeutic approaches.

neuroscience↗