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Urosevic, M.

Publications and source records attributed to Urosevic, M..

3 recordsLinked to original sources

Structural and dynamic embedding of the mouse functional connectome revealed by functional ultrasound imaging (fUSI)

Functional ultrasound imaging (fUSI) is an emerging hemodynamic neuroimaging modality whose potential for connectome-scale network mapping remains largely untested. Here, we establish a non-invasive transcranial fUSI protocol and an fMRI-inspired preprocessing framework that enable robust resting-state functional connectomics in the mouse. We show that fUSI resolves canonical brain-wide cortical and subcortical networks with high spatial concordance to fMRI, including a default-mode (DMN) and a laterocortical network. Notably, fUSI networks are robustly embedded within the structural connectome, with structure-function coupling being parsimoniously described by four dominant axes that differentially relate functional systems to known anatomical substrates. We also show that, beyond static organization, fUSI reproduces hallmark resting state fMRI dynamics, including dominant anti-correlated coactivation patterns (CAPs) and a structured transition architecture that converges onto three stable attractor modes. Together, these results establish transcranial fUSI as a portable and scalable complement to fMRI for connectome-scale mapping of mouse brain networks.

neuroscience↗

Evidence-based guidelines for improving network detectability in rodent fMRI

Mouse resting-state functional magnetic resonance imaging (rs-fMRI) is an increasingly popular tool for probing brain activity under experimental manipulations; however, there remains considerable variability in data quality throughout the field. There is a need for an accessible set of acquisition guidelines such that a baseline level of data quality can be attained regardless of domain expertise or specialized equipment (i.e. in anesthetized, free-breathing mice). In particular, there is a gap in the literature regarding the interpretation of physiological parameters as markers of anesthetic depth, and ultimately, data quality. To this end, we developed a set of acquisition guidelines after examining whether continuous physiological variables predict network detectability above and beyond categorical external variables (anesthetic dose, session, time) in C57Bl/7 and C3HeB/FeJ mice anesthetized with isoflurane-dexmedetomidine. Standard physiological metrics (respiration rate and heart rate) did not predict network detectability above and beyond anesthetic dose but instead depended strongly on strain and subject, thus we advise against tuning anesthesia based on respiration or heart rate when the goal is obtaining clear resting-state networks. The most important predictor of improved network detectability was a low isoflurane dose of 0.23%, hence we recommend that researchers prioritize piloting the minimal possible isoflurane dose for their mouse model. In summary, our work examines the contributions from sources of variability that impact rs-fMRI data quality and synthesizes the findings into practical guidelines to help experimenters adapt their acquisition protocols and improve data quality.

neuroscience↗

Examining Alzheimer's Disease Modifiable Risk Factors: Impact of Physical Activity and Diet on Neuroanatomy and Behaviour in Mice

Dementia is a global public health challenge, with obesity emerging as an important modifiable risk factor. Here, we examined whether lifestyle interventions can mitigate the effects of diet-induced obesity on body weight, behaviour, and brain anatomy in mouse models. Using a longitudinal design, wild-type and triple-transgenic (3xTgAD) mouse models of Alzheimers disease were exposed to a high-fat diet and assigned to one of three interventions: voluntary physical activity, a low-fat diet, and their combination. A high-fat diet significantly increased body weight and induced widespread neuroanatomical changes, with effects modulated by sex and genotype. The combined intervention led to significant weight loss in males of both genotypes. Neuroanatomical analyses revealed that a high-fat diet significantly reduced hippocampal and cerebellar volumes in wild-type mice but had a less pronounced effect on 3xTgAD mice; nevertheless, interventions, particularly the combined approach, increased localized brain volumes in these regions regardless of genotype. Multivariate integration of behavioural and neuroanatomical measures identified a brain pattern linking hippocampal and cerebellar volumes to intervention and behavioural performance. Spatial gene enrichment analysis of this pattern identified biological processes, including glucose homeostasis, as potential biological mechanisms underlying intervention effects. Overall, these findings suggest that voluntary physical activity and a low-fat diet can modulate brain structure and behaviour, partially counteracting the effects of a high-fat diet, and potentially recruiting biological processes that may support brain health.

neuroscience↗