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Scheel, N.

Publications and source records attributed to Scheel, N..

3 recordsLinked to original sources

Longitudinal diffusion tensor imaging identifies coordinated white matter remodeling during cocaine self-administration in mice

White matter microstructural alterations are increasingly recognized as a feature of cocaine use disorder (CUD), yet the longitudinal progression and biological underpinnings of these changes remain poorly understood. Although rodent intravenous self-administration (IVSA) provides a translational model of voluntary cocaine use, longitudinal diffusion tensor imaging (DTI) has not previously been combined with cocaine IVSA in mice. Here, we established a longitudinal IVSA-DTI framework to characterize white matter microstructural remodeling during cocaine self-administration and early withdrawal. Male C57BL/6 mice underwent DTI at baseline, following 11 consecutive days of cocaine (0.5 mg/kg/infusion) or saline IVSA, and after a 7-day withdrawal period immediately following a cocaine-seeking test (n = 4/group). Fractional anisotropy (FA) was evaluated longitudinally using atlas-based region-of-interest analyses and whole-brain diffusion maps. Cocaine-treated mice acquired robust operant responding and exhibited coordinated longitudinal FA alterations across interconnected hippocampal-associated white matter pathways. The most consistent changes occurred within the bilateral dorsal hippocampal commissure, fornix, and fimbria, with cocaine-treated mice demonstrating increased FA during self-administration relative to baseline while saline controls exhibited smaller or opposing longitudinal changes. Difference-in-differences maps further demonstrated cocaine-associated FA alterations within hippocampal pathways and localized regions of the corpus callosum after accounting for longitudinal changes in saline controls. These findings establish the feasibility of combining longitudinal DTI with cocaine IVSA in mice and demonstrate coordinated white matter microstructural remodeling during voluntary cocaine exposure. This framework provides a translational platform for future studies integrating longitudinal neuroimaging with genetically modified mouse models, tractography, and histological validation to investigate the mechanisms underlying cocaine-associated white matter plasticity.

neuroscience↗

A Functional Resting-State Network Atlas Based on 420 Older Adults with Hypertension

The Risk Reduction for Alzheimers Disease (rrAD) trial included 513 cognitively normal, sedentary, hypertensive older adults (aged 60 to 85 years) with dementia risk factors. We utilized 420 high-quality baseline resting-state functional MRI (rs-fMRI) scans from this cohort to develop a functional atlas tailored for aging populations. Typical rs-fMRI atlases derived from healthy young adults do not account for age-related changes, such as cortical atrophy, enlarged ventricles, and altered connectivity. To address this gap, we created a cohort-specific MNI-adjacent anatomical template, rrAD420, using SPM12s DARTEL registration. In this space, we derived a comprehensive functional atlas using both group independent component analysis (GICA) and probabilistic functional mode decomposition (PROFUMO). The rrAD420 atlas offers detailed representations of Resting-State Network (RSN) connectivity, encompassing unique configurations and overlapping interactions. It features two Default-Mode Network (DMN)-specific seed-based maps (DMN24 with cerebellum, DMN18 without) and data-driven components resembling the major RSNs. Furthermore, PROFUMO allowed for the identification of multimodal and combinatory networks, capturing connections within and between RSNs. While optimized for hypertensive older adults, the rrAD420 atlas serves as a versatile tool for broader aging populations, aiding in the study of neurodegenerative processes and biomarker discovery.

neuroscience↗

Novel inductively-coupled ear-bars (ICEs) for fMRI signal enhancement in rat entorhinal cortex

Entorhinal cortex (EC) is a potential target of deep brain stimulation in Alzheimers disease (AD) and fMRI can enable whole-brain dynamic mapping noninvasively. However, it remains challenging to study EC-based fMRI connectivity in rodents due to image signal loss and the lower sensitivity of the surface coil ring or array coil for deep brain areas. To reduce the magnetic susceptibility artifacts driven signal loss issue, we introduced baby cream into the middle ear. To improve detection sensitivity, we implemented novel inductively-coupled ear-bars (ICEs) in the 7 T Bruker scanner, which resulted in an approximately 2-fold signal-to-noise ratio (SNR) increase in EC over the conventional surface array. The ICE can be conveniently utilized as an add-on device, with no modulation to the scanner interface. To demonstrate the applicability of ICEs for both task and resting-state (rs) fMRI, whole-brain echo-planar imaging (EPI) was performed in anesthetized rats modeling AD mixed dementia. Seed-based rs-fMRI connectivity maps emanating from the left entorhinal cortex demonstrated its connectivity to the hippocampus, piriform cortex, septal nuclei, and prefrontal cortex. Hence, this work demonstrates an optimized procedure for ICE by acquiring large scale networks emanating from a seed region that was not easily accessible by conventional MRI detectors, enabling better observation of EC-based brain fMRI connectivity studies with a higher signal-to-noise ratio in rodent models of dementia.

neuroscience↗